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PubMed2001

Are risk factors the same for small for gestational age versus other preterm births?

OBJECTIVES: This article explores whether the impact of social and demographic risk factors for preterm birth differs for small for gestational age preterm births versus other preterm births. STUDY DESIGN: This was a European case control study of the determinants of preterm birth (4700 cases and 6460 controls). Small for gestational age and non-small for gestational age preterm births were compared with a control group of term births; relationships were explored further by stratifying preterm births into subgroups by mode of onset, the presence of hypertension, and gestational age. RESULTS: Of the social and demographic risk factors for preterm birth identified in this sample, high maternal age, smoking, and low and high maternal body mass index have a stronger effect on small for gestational age preterm births. In contrast, obstetric history, maternal education, and marital status have similar effects regardless of birth weight. Hypertension during pregnancy is strongly associated with small for gestational age preterm birth and contributes to an explanation of observed differences. CONCLUSIONS: These results underline the importance of considering fetal growth restriction in the analysis of risk factors for preterm birth.

Adult↗

PubMed2002

Maternal plasma corticotropin-releasing hormone trajectories vary depending on the cause of preterm delivery.

OBJECTIVE: Although second trimester maternal plasma corticotropin-releasing hormone concentrations are elevated in women who are destined to deliver preterm, the sensitivity and positive predictive value of an individual test of corticotropin-releasing hormone concentration is low. This poor screening performance may be due in part to the observation that the causes of preterm delivery are heterogenous, with potentially different effects on corticotropin-releasing hormone production. We have reanalyzed data from a previous cohort of women with multiple samplings to determine whether the trajectory of increase of placental corticotropin-releasing hormone provided more information than did a single sample. STUDY DESIGN: In this cohort, where 2 to 4 samples that had been assayed for corticotropin-releasing hormone were available on 305 women, the general form of the exponential equation y = ae(bt) was fitted to the corticotropin-releasing hormone data of each individual by the Gauss-Newton nonlinear least squares method, which generated the parameters, y-intercept and rate of rise, in corticotropin-releasing hormone concentration for each woman. Nonparametric statistical techniques, including bootstrapping, were applied to compare the results for the group of women who delivered at term with the group of women who delivered spontaneously preterm and the group of women who were delivered preterm by induction or cesarean delivery because of obstetric indication. RESULTS: The 3 clinically defined groups have significantly different parameters, y-intercept and rate of rise, which describe the corticotropin-releasing hormone trajectory. The group that delivered preterm because of obstetric indications had a similar mean y-intercept but significantly greater mean rate of rise in corticotropin-releasing hormone concentration than the term group (0.3491 vs 0.1788; 95% CI, 0.2331-0.4615 vs 0.1394-0.2330). The group that delivered spontaneously preterm had a significantly greater mean y-intercept than the group that delivered preterm because of obstetric indication (17.08 vs 1.83; 95% CI, 5.89-28.43 vs 0.03-5.19) but a similar mean rate of rise to the group that delivered at term. CONCLUSION: These data suggest that spontaneous preterm delivery is associated with an abnormal setting of the production of corticotropin-releasing hormone that is present from very early in pregnancy, although women who experience an induced preterm delivery are characterized by rapidly rising placental corticotropin-releasing hormone concentrations. These data further suggest that clinical abnormalities that are associated with preterm delivery by induction or cesarean delivery are associated with abnormalities that lead to a rapidly increasing corticotropin-releasing hormone concentrations. Trajectories for corticotropin-releasing hormone provide information beyond that obtained from a single sample.

Cesarean Section↗

PubMed2006

Brainstem auditory evoked response at term in preterm infants after perinatal hypoxia-ischaemia.

AIM: To examine brainstem auditory function in preterm infants after perinatal hypoxia-ischaemia (HI). METHODS: Brainstem auditory evoked response (BAER) was studied at 37-42 wk postconceptional age in preterm infants who suffered perinatal HI, and were compared with those in preterm and term infants without any major perinatal problems. RESULTS: None of the latencies of waves I, III and V in the BAER in preterm infants after perinatal HI differed significantly from those in preterm and term controls. There were also no significant differences in the I-V and I-III interpeak intervals between preterm infants after HI and the controls. However, III-V interval in infants after HI tended to increase, and was significantly longer than in term controls (p<0.01), although it did not differ significantly from that in preterm controls. Similarly, the III-V/I-III interval ratio was greater than in term controls (p<0.05), but was similar to that in preterm controls. All amplitude variables did not differ significantly from the controls. CONCLUSION: BAER in preterm infants after perinatal HI did not differ significantly from that in preterm infants without perinatal problems, but differed slightly from that in normal term infants. The prolonged III-V interval as compared with the term controls suggests a minor impairment in central auditory function.

Evoked Potentials, Auditory, Brain Stem↗

PubMed2002

A prospective study of vaginal pH as a predictor of preterm delivery.

OBJECTIVE: To test the usefulness of vaginal pH determinations in the prediction of the risk of preterm delivery at or before 36 weeks of gestation. METHODS: This was a prospective study of asymptomatic pregnant women. Vaginal pH was determined using pH paper in a sterile speculum examination during prenatal visits. Patients were followed to delivery and hospital records were reviewed to extract obstetric information. A total of 308 women agreed to participate and met the criteria for enrolment. Preterm delivery was defined as delivery at or prior to 36 weeks of gestation. Abnormal pH was defined as a pH of > 5.0. RESULTS: Abnormal vaginal pH was associated with increased risk of preterm delivery, (OR 3.3, 95% CI 1.15, 9.2; p = 0.02). In the first trimester, an abnormal vaginal pH was not associated with preterm delivery (p = 0.3). After the first trimester, a vaginal pH of 5.0 or greater was associated with increased risk of preterm delivery (OR 9.6, 95% CI 2.0, 45.5; p = 0.001) as well as delivering an infant of less than 2500 g (OR 3.1, 95% CI 1.2, 7.8; p = 0.015). History of a previous preterm delivery was associated with increased risk of preterm delivery (OR 6.2, 95% CI 1.6, 23.7; p = 0.02). A logistic regression model used to control for a history of preterm delivery and race showed abnormal vaginal pH to remain as an independent predictor of preterm delivery (p = 0.01). CONCLUSIONS: High vaginal pH (> or = 5.0) identified women at risk for preterm delivery.

Adult↗

PubMed2002

Incidence, obstetric risk factors and pregnancy outcome of preterm placental abruption: a retrospective analysis.

OBJECTIVE: To determine obstetric risk factors for the occurrence of preterm placental abruption and to investigate its subsequent perinatal outcome. STUDY DESIGN: A retrospective comparison of all singleton preterm deliveries complicated with placental abruption, between the years 1990-1998, to all singleton preterm deliveries without placental abruption, in the Soroka University Medical Center. RESULTS: Placental abruption complicated 300 (5.1%) of all preterm deliveries (n = 5934). A backstep multivariable analysis found the following factors to be independently correlated with the occurrence of preterm placental abruption: grandmultiparity (more than five deliveries), early gestational age, severe pregnancy-induced hypertension, previous second-trimester bleeding and non-vertex presentation. These pregnancies had a significantly lower rate of preterm premature rupture of membranes than preterm pregnancies without placental abruption. Pregnancies complicated with preterm placental abruption had significantly higher rates of cord prolapse, non-reassuring fetal heart rate patterns, congenital malformations, Cesarean deliveries, perinatal mortality, Apgar scores lower than 7 at 5 min, postpartum anemia and delayed discharge from the hospital than did preterm deliveries without placental abruption. In order to assess whether the increased risk for perinatal mortality was due to the placental abruption, or due to its significant association with other risk factors, a multivariable analysis was constructed with perinatal mortality as the outcome variable. Placental abruption (OR 3.0, 95% CI 2.1-4.1) as well as cord prolapse, previous perinatal death, low birth weight and congenital malformations were found to be independent risk factors for perinatal mortality. CONCLUSION: Preterm placental abruption is an unpredictable severe complication associated with significant perinatal morbidity and mortality. Factors found to be independently associated with placental abruption were grandmultiparity, severe pregnancy-induced hypertension, malpresentation, earlier gestational age and a history of second-trimester vaginal bleeding.

Abruptio Placentae↗

PubMed2001

Ultradian and circadian activity-rest rhythms of preterm neonates compared to full-term neonates using actigraphic monitoring.

During the first weeks of life, preterm neonates show fewer circadian rhythms in their physiological parameters than full-term neonates. To determine whether preterm neonates differ in their temporal adaptation to the day-night cycle from full-term neonates at the early age of 1 week, we compared activity-rest behavior of both groups. Activity-rest behavior of 10 neurologically healthy preterm neonates (born in 34th to 36th week of gestation) and 10 neurologically healthy full-term neonates (born in 37th to 42nd week of gestation) was monitored longitudinally for 8 successive days in the first 2 weeks of life. Actigraphy was used to register and display time patterns of activity and rest in neonates by using small actometers, which resemble a wristwatch. Nursing/feeding was recorded using the actometer's integrated event marker button. Recordings for preterm neonates were conducted in the hospital, recordings for full-term neonates were carried out in the hospital and in their homes. In addition to the actigraphic recordings, a standardized diary was kept regularly. To assess periodic characteristics, frequency components of activity-rest behavior were analyzed using fast Fourier transformation (FFT). Amounts of daily sleep time, nightly sleep time, and sleep time during 24h were compared. Nursing/feeding epochs were also analyzed for 5 preterm and 5 full-term neonates to compare their food intake behavior. The majority of preterm neonates showed a multitude of ultradian frequencies in their spectra. In contrast, several full-term neonates showed a distinct circadian frequency. In preterm neonates, average nightly sleep and average daily sleep of all recorded days were very similar, but after the fourth day of life, only average nightly sleep increased. In full-term neonates, average nightly and daily sleep time of all recorded days differed by about 1h. Average sleep time during 24h for preterm and full-term neonates was similar. Preterm neonates showed longer intervals between events of food intake than full-term neonates. The circadian peaks in the frequency spectra of full-term neonates may indicate the initial adaptation in the first week of life to a 24h day. This is in agreement with our results concerning the different durations of nightly and daily sleep. The increase in nightly sleep time of preterm neonates may be attributed to the progressing adaptation to a circadian activity-rest pattern.

Activity Cycles↗

PubMed2004

Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: a prospective and longitudinal study during the first year of life.

Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3)) (radioimmunoassay) were measured in the mother and in the cord at delivery and in the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6 months, and 12 months of postnatal age. These values were compared to those of healthy full-term infants of the same postnatal age (22 at 24 hours from our hospital and from previously reported data at others times). Mean 24-hour TSH values were significantly lower (p < 0.001) in preterm than in full-term infant populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL); however, all TSH values of preterm infants were in the range of the full-term values. Mean 24-hour free T(4) values were similar in preterm and full-term infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants had free T(4) values within the range of those of full-term infants at 24 hours. Mean T(4) and T(3) values were significantly lower in preterm than in full-term neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were significantly higher in preterm than in full-term newborns. From 1 week onwards, all thyroid function values were in the same range in both populations. In conclusion, individual thyroid function was similar in healthy preterms and full-terms from the first 24 hours of life. Normative data in preterm infants during the first year of life applying the latest luminescence techniques currently used worldwide are reported.

Case-Control Studies↗

PubMed1999

Social differences of very preterm birth in Europe: interaction with obstetric history. Europop Group.

Social differences of very preterm birth (22-32 completed weeks of amenorrhea) were studied using data from a large case-control survey in Europe between 1994 and 1997; 1,675 very preterm births and 7,965 full-term births were included. The relation between social factors and very preterm birth was studied according to obstetric history and the mode of delivery onset. Very preterm birth was significantly related to low educational level among women with no previous adverse pregnancy outcome (odds ratio (OR) = 2.67, 95 percent confidence interval (CI) 1.66-4.28) and among primigravid women and those with previous first-trimester abortion (OR = 2.01, 95 percent CI 1.56-2.58). In this group, unemployment of all household members was associated with a double risk of very preterm birth. No significant association between very preterm birth and socioeconomic status was observed among women with previous second-trimester abortion or preterm birth. Socioeconomic indicators remained significantly associated with both spontaneous and induced very preterm births among women with no previous late fetal loss or preterm birth. The results are consistent with social factors affecting the risk of very preterm birth, but the relation differs according to obstetric history.

Adolescent↗

PubMed2000

Antibiotics and preterm labor.

In summary, a definite association has been demonstrated between preterm labor and genital tract infection. Conclusions regarding the true benefits of antibiotics as adjunctive therapy in treatment of preterm labor are inconsistent. Whereas some of the studies were able to demonstrate significant prolongation of pregnancy, no consistent reduction in either maternal or neonatal morbidity has been demonstrated. However, because the actual incidental morbidity rate is low in the populations studied, the power of this finding is also low. The potential risks for using antimicrobials has yet to be adequately addressed. It has been shown that bacterial resistance can develop when antibiotics are used without specific aim or when a specific bacteria is undertreated. It has been recently shown that prenatal and intrapartum antibiotic use is associated with an increased risk for antibiotic resistant neonatal sepsis if infection occurs. Because of these reasons, we discourage the administration of antibiotic treatment to women in preterm labor for the purpose of pregnancy prolongations. Treatment should be directed towards those with specific indications for treatment (e.g., intrapartum, group B streptococci prophylaxis, urinary tract infection, etc). The primary flaw in these many evaluations of preterm labor is the true incidence of preterm birth. The clinical diagnosis of preterm labor is a difficult one. Approximately one-half of those individuals with preterm contractions will not deliver until term. So, the use of antibiotics for all women in idiopathic preterm labor is destined to treat many women who are unlikely to benefit. If we were able to truly identify those who were in "true" labor, perhaps we could be more selective in determining who may benefit from antibiotics. Biochemical markers such as onco-fetal fibronectin could well-be a helpful marker. Goldberg et al evaluated FFN in vaginal and cervical secretions while attempting to better-predict who would have upper genital tract infection. In this large, multicenter trial, patients were tested for FFN every 2 weeks from 23 to 30 weeks gestation. In those patients who proceeded to deliver before 32 weeks gestation, increased levels of cervical FFN (> 50 ng/ml) were identified in approximately one-quarter. Fetal fibronectin was positive in 4% of their samples and was found to be twice as likely in one with bacterial vaginosis. They showed that the presence of increased FFN was associated with upper genital tract infection (clinical and histologic chorioamnionitis) as a main reason for preterm labor and delivery (increased risk 16-20-fold). Those with increased FFN levels were also shown to have an increased incidence of neonatal sepsis as well. Peaceman et al used FFN to attempt to identify those at risk for preterm delivery among women with contractions between 24 and 34 6/7 weeks gestation. Those with negative FFN were less likely to deliver within 7 days of the test. The negative predictive value was 99.7%, suggesting that this test may be helpful in identifying women who would not benefit from antibiotic treatment. However, if in the absence of prospective clinical trials demonstrating the efficacy of this approach, we discourage the use of FFN screening for this indication.

Anti-Bacterial Agents↗

PubMed2005

Transvaginal ultrasonography of the cervix to predict preterm birth in women with uterine anomalies.

OBJECTIVE: Women with uterine anomalies have higher rates of preterm birth, but the reason for this has not been elucidated. Transvaginal ultrasound examination has been shown to be an accurate test for the prediction of preterm birth but has not been studied specifically in this population. METHODS: Pregnant women with uterine anomalies were followed prospectively with transvaginal ultrasound examination of the cervix, performed between 14 and 23 6/7 weeks of gestation. A short cervical length was defined as less than 25 mm of cervical length. The primary outcome was spontaneous preterm birth, defined as birth at less than 35 weeks. RESULTS: Of the 64 pregnancies available for analysis, there were 28 with a bicornuate uterus, 13 with a septate uterus, 11 with a uterine didelphys, and 12 with a unicornuate uterus. The overall incidence of spontaneous preterm birth at less than 35 weeks was 11%. Of the 10 (16%) women with a short cervical length, 5 (50%) had spontaneous preterm birth. Of the 54 women without a short cervical length, only 2 (4%) had a spontaneous preterm birth. The sensitivity, specificity, and positive and negative predictive values of a short cervical length for spontaneous preterm birth were 71%, 91%, 50%, and 96%, respectively (relative risk 13.5, 95% confidence interval 3.49-54.74). Of the 7 women with both short cervical length and preterm birth, all uterine subtypes were represented except septate uterus. CONCLUSION: A short cervical length on transvaginal ultrasonography in women with uterine anomalies has a 13-fold risk for preterm birth. Unicornuate uterus had the highest rate of cervical shortening and preterm delivery. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2006

Transvaginal ultrasonography in the prediction of preterm birth after treatment for cervical intraepithelial neoplasia.

OBJECTIVE: To estimate whether cervical length measured by transvaginal ultrasonography in women having had loop electrosurgical excision procedure (LEEP), cold knife conization, or cryotherapy predicts spontaneous preterm birth. METHODS: Women with a history of LEEP, cold knife conization, or cryotherapy and who were subsequently pregnant with singleton gestations were prospectively compared with both a low-risk control group and women with previous spontaneous preterm birth. A transvaginal ultrasonogram measuring cervical length was performed at 24 to 30 weeks of gestation. Primary outcomes included cervical length and spontaneous preterm birth less than 37 weeks. Secondary outcomes were spontaneous preterm birth less than 34 weeks, low birth weight, and maternal and neonatal outcomes. RESULTS: Women with previous LEEP (N = 75), cold knife conization (N = 21), and cryotherapy (N = 36) had shorter cervical lengths (3.54, 3.69, and 3.75 cm respectively) than the low-risk control group (N = 81, 4.21 cm) (P < .001, P = .03, P = .02 respectively) and similar lengths to women with a previous spontaneous preterm birth (N = 63, 3.78 cm). Loop electrosurgical excision procedure and cold knife conization, but not cryotherapy, were associated with spontaneous preterm birth less than 37 weeks (odds ratio 3.45, 95% confidence interval 1.28-10.00, P = .02; and odds ratio 2.63, 95% confidence interval 1.28-5.56, P = .009, respectively). Using a cutoff of 3.0 cm, transvaginal ultrasonography had a positive predictive value of 53.8% and negative predictive value of 95.2% for spontaneous preterm birth less than 37 weeks in women with LEEP. CONCLUSION: Women with a history of LEEP, cold knife conization, and cryotherapy all independently have shorter cervical lengths than low-risk controls and similar lengths to women with previous spontaneous preterm birth. Loop electrosurgical excision procedure and cold knife conization are associated with spontaneous preterm birth less than 37 weeks, and transvaginal ultrasonography predicts preterm birth in women who have had LEEP. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2006

Temporal trends of preterm birth subtypes and neonatal outcomes.

OBJECTIVE: To describe temporal trends of preterm birth subtypes, neonatal morbidity, and hospital neonatal mortality. METHODS: A database of 1.7 million births that occurred in 51 maternity hospitals in Latin America from 1985 to 2003 was studied. Subgroups of preterm births were classified according to the presence or absence of maternal medical or obstetric complications, spontaneous labor, preterm labor after premature rupture of membranes, induction of labor, or elective cesarean. Outcomes studied, for different periods, were prevalence of small for gestational age, neonatal morbidity, and neonatal mortality. RESULTS: Spontaneous preterm labor without maternal complications was the most frequent subtype of preterm birth (60%), followed by premature rupture of membranes without maternal complications. Preterm births due to elective induction and delivery by elective cesarean increased markedly in the last 20 years, from 10% in 1985-1990 to 18.5% in recent years. Neonates born after spontaneous labor without maternal complications had the lowest mortality rate, but their large numbers made them responsible for one half of the preterm mortality. The induction followed by elective cesarean subgroups accounted for 13.4% of the preterm deaths between 1985 and 1990 and increased to 21.2% between 1996 and 2003. CONCLUSION: Spontaneous labor in mothers without maternal complications is the most frequent cause of preterm births and is also the most important subgroup related to neonatal mortality. However, preterm births due to induction of labor or elective cesarean are increasing in Latin America and are becoming important contributors to neonatal mortality.

Adult↗

PubMed2006

Respiratory consequences of preterm birth.

Approximately 8% of Australia's 250,000 annual births occur preterm (before 37 weeks completed gestation). Preterm infants represent 75% of all neonatal deaths in Australia, with the vast majority of these deaths caused by pulmonary disease. 2. The respiratory consequences for survivors of preterm birth include the immediate challenges of breathing with underdeveloped lungs, usually manifest as respiratory distress syndrome (RDS), and, in the long term, with persisting pulmonary abnormalities. Therapies to prevent neonatal lung disease now permit survival of preterm infants born as early as 22 weeks gestational age, but not without consequences. 3. Preterm infants are at risk of developing chronic lung disease/bronchopulmonary dysplasia (BPD). The lungs of infants dying from BPD are inflamed and have fewer, larger alveoli than normal and exhibit abnormal pulmonary vascular development. There is now a growing appreciation of the contribution of intrauterine inflammation to the aetiology of BPD. 4. Impaired airway function is commonly reported in follow-up studies of children born preterm. Decreased expiratory flow rates have been associated with preterm birth per se, but airway function appears more affected in survivors of RDS and BPD. Observations in survivors of BPD suggest persisting abnormalities in the structure of the lung parenchyma and airways. 5. Follow-up studies of preterm infants into adulthood are lacking, as are experimental examinations of the long-term physiological and anatomical effects of preterm birth. Both are necessary to understand the causes of the long-term respiratory consequences of preterm birth.

Female↗

PubMed1997

Are sociodemographic factors predictive of preterm birth? A reappraisal of the 1958 British Perinatal Mortality Survey.

OBJECTIVE: Reassessment of the predictive value of sociodemographic factors on preterm birth. DESIGN: Population-based case-control study. SETTING: England, Wales and Scotland. SAMPLE: The study sample consisted of 5630 primiparous and 9538 multiparous women who were delivered during the first week of March 1958 in Britain. Multiple births were excluded. METHOD: Factors potentially predictive of preterm birth were assessed for primiparous and multiparous women separately, using the split-sample cross-validation technique. MAIN OUTCOME MEASURE: Preterm birth, defined as birth occurring before 259 days of gestation. RESULTS: Preterm birth rates for primiparous and multiparous women were 54 and 53 per 1000 births, respectively. In primiparous women low maternal age (under 20 years) was the only sociodemographic variable that was predictive of preterm birth (P = 0.01). However, only 10.7% of preterm birth among primiparous women was associated with low maternal age. In multiparous women, using univariable analysis, employment status was statistically significantly associated with preterm birth. This association disappeared when employment status was adjusted for by other variables in the model. Social class was not predictive of preterm birth in either primiparous or multiparous women. CONCLUSION: From the results of this study it is concluded that sociodemographic factors do not have a substantial impact on the risk of preterm birth. It seems unlikely that preventative measures aimed at social-demographic adversity will reduce preterm birth rates.

Case-Control Studies↗

PubMed1999

Very and moderate preterm births: are the risk factors different?

OBJECTIVE: To describe the risk factors for very preterm births and to compare the strengths of the associations between these risk factors and very and moderate preterm births. DESIGN: A case-control study. SETTING: Fifteen European countries. METHODS: Between 1994 and 1997, 1675 very preterm births, 3652 moderate preterm births and an unmatched control group of 7965 births at term were included. Odds ratios for very and moderate preterm births (related to socioeconomic status, behavioural factors, maternal age, body mass index and obstetric history) were estimated and compared using polytomous logistic regression. RESULTS: Underprivileged social situation, older maternal age and adverse previous pregnancy outcomes were significantly related to very and moderate preterm births. However, these factors were more strongly associated with very preterm births than with moderate preterm births, for both spontaneous and induced deliveries. Smoking during pregnancy, young maternal age and low body mass index were significantly related to very and moderate spontaneous preterm births, but no significant difference in odds ratios was observed between the two outcomes. CONCLUSION: These results suggest that risk factors for very and moderate preterm births are similar, but the strength of the associations differ, especially for social factors and obstetric history.

Adult↗

PubMed2005

Role of cytokines in preterm labour and brain injury.

Intrauterine infection induces an intra-amniotic inflammatory response involving the activation of a number of cytokines and chemokines which, in turn, may trigger preterm contractions, cervical ripening and rupture of the membranes. Infection and cytokine-mediated inflammation appear to play a prominent role in preterm birth at early gestations (<30 weeks). The role of infection/inflammation in preterm birth in Europe has been incompletely characterised. The rate of preterm birth in Sweden is lower, and the rate of chorioamnionitis, bacterial vaginosis (BV), neonatal sepsis, and urinary tract infections during pregnancy is lower compared with the USA. In a Swedish population of women with preterm labour or preterm premature rupture of the membranes (PPROM) <34 weeks of gestation, microorganisms were detected in the amniotic fluid in 25% of women with PPROM and in 16% of those in preterm labour. Nearly half of these women had intra-amniotic inflammation defined as elevated interleukin-6 (IL-6) and IL-8, and there was a high degree of correlation between cytokine levels and preterm birth or the presence of microbial colonisation. These data do not support the hypothesis that infection-related preterm birth is less frequent in northern Europe than elsewhere. The intra-amniotic inflammatory response has also been associated with white matter injury and cerebral palsy. We find that in experimental models, induction of a systemic inflammatory response using lipopolysaccharide activates toll-like receptors (TLRs), which produce either white matter lesions or increase brain susceptibility to secondary insults. Recently, IL-18 in umbilical blood was shown to correlate with brain injury in preterm infants and IL-18 deficiency in mice decreases CNS vulnerability.

Brain Diseases↗

PubMed2005

Secondary predictors of preterm labour.

In addition to primary predictors of preterm birth which are used to estimate the baseline risk of preterm birth, secondary predictors (based on examinations done during the current pregnancy) allow a more accurate assessment of the risk of preterm birth in individual women. Screening for early signs of spontaneous preterm labour has always been an important topic in obstetric care. During the last two decades, the detection of fetal fibronectin (FFN) from cervicovaginal secretions and cervical shortening diagnosed by transvaginal ultrasonography have emerged as the major secondary predictors of preterm birth. Both markers have been extensively studied and consistently shown to be strong short term predictors of preterm birth across a wide range of gestational ages. Other secondary predictors that confirm the role of intrauterine infection in the pathogenesis of preterm birth are bacterial vaginosis (BV) and elevated levels of interleukin (IL)-6, IL-8, ferritin and granulocyte colony-stimulating factor. Apart from BV, inflammatory markers are still not routinely used. The sensitivity of single markers in predicting preterm birth is only moderate and serial examinations of markers, combinations of different markers and multiple marker tests have been studied, with limited results. Studies of interventions in order to prevent preterm birth have also yielded mixed benefits, as a consequence of which the use of these markers to screen low risk pregnancies is generally not recommended. Currently, secondary predictors of preterm birth are used mainly to design new intervention studies tailored to specific high risk populations and to avoid unnecessary interventions in the management of high risk women.

Biomarkers↗

PubMed2005

Can antibiotics prevent preterm birth--the pro and con debate.

Studies using different diagnostic methods and outcome parameters have used different antibiotics and dose/administration regimes to women of differing risk of preterm birth with, not surprisingly, different results. Studies which have shown benefit have been criticised for having either poor methodology, low sample size or having only showed benefit after a non-prespecified subgroup analysis. Studies which have failed to show any benefit have been criticised for unacceptable methods of diagnosing abnormal genital tract flora or having excluded a large percentage of patients eligible for the study, for having permitted a long period to elapse from diagnosis of abnormal genital tract flora to administration of treatment and for having employed treatment too late in pregnancy. A Cochrane Systematic Review of these studies failed to provide a definitive answer because this was published one month before two randomised double-blind placebo-controlled trials were published, in which clindamycin used either systemically or intravaginally in low risk, unselected women resulted in a 60% reduction in the incidence of preterm birth. This would have influenced the inconclusive results of the Cochrane review, with respect to general population studies. Very early spontaneous preterm labour and preterm birth is more likely to be of infectious aetiology than preterm birth just before term. The earlier in pregnancy at which abnormal genital tract flora is detected, the greater is the risk of an adverse outcome. Women with abnormal flora in early pregnancy, who subsequently revert to normal, continue to have a high risk of adverse outcome of pregnancy, at a degree similar to women with abnormal genital tract flora in early pregnancy who were treated with placebo. This suggests that whatever damage abnormal flora induces, this is at an early gestation, even if the flora subsequently reverts to normal. It follows therefore that if antibiotics are to be of help in preventing spontaneous preterm labour and preterm birth of infectious aetiology, these must be administered early in pregnancy. Antibiotics used prophylactically for the prevention of preterm birth are more likely to be successful if: they are used in women with abnormal genital tract flora (rather than other risk factors for preterm birth, e.g. low BMI, twins, generic previous preterm birth); they are used early in pregnancy prior to infection (tissue penetration/inflammation and tissue damage); they are used in women with the greatest degree of abnormal genital tract flora; and if they are used in women with a predisposition to mount a damaging inflammatory response to infection.

Anti-Bacterial Agents↗