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Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking.

STUDY OBJECTIVE: Research shows that neighbourhood socioeconomic factors are associated with preterm delivery. This study examined whether cigarette smoking and individual socioeconomic factors modify the effects of neighbourhood factors on preterm delivery. DESIGN: Case-control study. SETTING: Moffit Hospital in San Francisco, California. PARTICIPANTS: 417 African American and 1244 white women, including all preterm and a random selection of term deliveries 1980-1990, excluding non-singleton pregnancies, congenital anomolies, induced deliveries, and women transported for special care. US census data from 1980 and 1990 were used to characterise the women's neighbourhoods, defined as census tracts. RESULTS: Cigarette smoking increased the risk of preterm delivery among both African American (OR=1.77, 95% confidence intervals (CI) (1.12 to 2.79)) and white women (OR=1.25, 95% CI (1.01 to 1.55)). However, cigarette smoking did not attenuate or modify the association of neighbourhood factors with preterm delivery. Among African American women, having public insurance modified the relation between neighbourhood unemployment and preterm delivery; among women without public insurance, the risk of preterm delivery was low in areas with low unemployment and high in areas with high unemployment, while among women with public insurance the risk of preterm delivery was highest at low levels of neighbourhood unemployment. CONCLUSIONS: Cigarette smoking was associated with preterm delivery, especially among African Americans. Adverse neighbourhood conditions had an influence on preterm delivery beyond that of cigarette smoking. The effects of some neighbourhood characteristics were different depending on individual socioeconomic status. Examining socioeconomic and behavioural/biological risk factors together may increase understanding of the complex causes of preterm delivery.

Black or African American↗

Recurrence risk of preterm birth due to preeclampsia.

There may be an increased risk of preterm birth due to preeclampsia among women whose previous pregnancies ended in preterm birth due to preeclampsia. We studied 1,130 women who delivered 2 successive singleton infants in our hospital, excluding women who delivered an abnormally formed infant during the study period. We reviewed the gestational week at delivery in these 2,260 pregnancies and found a total of 182 preterm deliveries (8.1%) by 156 women. The causes of preterm birth were reviewed. Failed tocolysis, including premature rupture of membranes and clinical chorioamnionitis, and preeclampsia accounted for 135 (74.2%) and 30 (16.5%) of the 182 preterm deliveries, respectively. Women whose 1st delivery was preterm had a 3.26 times (95% CI 2.21-4.79) higher risk of a subsequent preterm delivery than women whose 1st delivery was term (26/96 vs. 60/1,034). The risk of preeclampsia-related preterm delivery was 54.4 times (17.2 to 172.5) higher in women with a previous preeclampsia-related preterm delivery than in women with a previous term delivery (5/19 vs. 5/1034). Women who had a history of preeclampsia-related preterm birth had a greater risk of preeclampsia-related preterm birth in a subsequent pregnancy as compared with women with a previous term birth.

Adult↗

Women's views of the preterm labor experience.

This study used a naturalistic approach to describe the childbearing woman's views of her preterm labor and delivery experience. Specifically, the aim was to identify how women describe, interpret, and manage preterm labor and subsequent preterm or term delivery. The views of 20 women who were hospitalized for preterm labor (before 37 weeks) were documented with semistructured, tape-recorded, in-depth interviews during their hospitalization for preterm labor and after delivery. Qualitative data analysis focused on the process of becoming a preterm labor patient and on living with a diagnosis of preterm labor. Women either waited for a period of time before seeking care or sought care immediately for the symptoms they were experiencing. Women interpreted the experience by identifying causes of preterm labor and by worrying about the outcome for the baby. Managing preterm labor required extensive, moderate, or limited changes in their lives. Women who delivered at term appeared to have more tangible help than those who delivered preterm. A better understanding of women's preterm labor experiences will provide clues to nurses on how to improve the care they provide.

Adolescent↗

Feeding preterm infants after hospital discharge: growth and development at 18 months of age.

We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (< or =1750 g birth weight, < or =34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0; p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.

Child Development↗

The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes.

The objectives of this study were 1) to evaluate interleukin-8 concentrations in cervical secretions in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes and 2) to compare the diagnostic value of interleukin-8 with fetal fibronectin determinations in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes. Interleukin-8 and fetal fibronectin were assayed in cervical secretions in 106 patients with singleton pregnancies and intact membranes admitted for preterm labor. Amniotic fluid obtained by amniocentesis was cultured and placentas (No = 43) analyzed for the presence of chorioamnionitis. The prevalence of pregnancies delivered preterm was 46.2% (49/106) and 15.09% (16/106) of amniotic fluid cultures were positive. Interleukin-8 levels in cervical secretions were significantly increased in patients who delivered preterm (p < or = 0.0001), in presence of positive amniotic fluid culture (p = 0.0016) and histological chorioamnionitis (p = 0.008) than in patients with negative findings. Receiver-operator characteristics curve analysis showed that an interleukin-8 value > 450 pg/ml is comparable to that of a fetal fibronectin value > 50 ng/ml in predicting preterm delivery (p = 0.247). Among patients who delivered preterm interleukin-8 concentrations > 860 pg/ml predicted a positive amniotic fluid culture with a sensitivity of 81.2% and a specificity 66.6%. Further, in patients who delivered preterm and had a negative amniotic fluid culture, IL-8 concentrations > 480 pg/ml predicted histological chorioamnionitis with a sensitivity 78.5% and specificity 61.5%. A positive fetal fibronectin > 50 ng/ml was not predictve of either a positive amniotic fluid culture or the presence of histological chorioamnionitis. In conclusion, increased concentrations of interleukin-8 and fetal fibronectin are associated with impending delivery and their diagnostic value seems comparable. However, interleukin-8 concentrations identify patients at risk of a positive amniotic fluid culture and the presence of histological chorioamnionitis. Measurement of interleukin-8 in cervical secretion is a non-invasive method to identify patients at risk for both preterm delivery and intrauterine infection.

Adult↗

A randomized, controlled trial of the effectiveness of an early-intervention program in reducing parenting stress after preterm birth.

BACKGROUND: Preterm birth has been associated with increased parenting stress in early infancy, and some reports have found this to be a risk factor for later behavioral problems. There are, however, few studies and conflicting results. Information about the fathers is scarce. OBJECTIVES: Our goal was to study the effects of an early-intervention program on parenting stress after a preterm birth until 1 year corrected age. METHODS: A randomized, controlled trial was conducted including infants with a birth weight <2000 g treated at the University Hospital of North Norway Trust, which serves the 2 northern-most counties in Norway, to examine the effects of a modified version of the Mother-Infant Transaction Program on parenting stress measured by the Parenting Stress Index. A term control group was also recruited. The Parenting Stress Index was administered to the mothers at 6 and 12 months' corrected age and to the fathers at 12 months' corrected age. The intervention consisted of 8 sessions shortly before discharge and 4 home visits by specially trained nurses focusing on the infant's unique characteristics, temperament, and developmental potential and the interaction between the infant and the parents. RESULTS: Seventy-one infants were included in the preterm intervention group, and 69 were included in the preterm control group. The preterm groups were well balanced. Seventy-four infants were included in the term control group. Compared with the preterm controls, both the mothers and fathers in the preterm intervention group reported significant lower scores in child domain, parent domain, and total stress on all occasions except the mother-reported child domain at 12 months. These differences were not related to birth weight or gestational age. The level of stress among the preterm intervention group was comparable to their term peers. Both parents in the intervention group reported consistently lower scores within the distractibility/hyperactivity, reinforces parents, competence, and attachment subscales compared with the preterm control group. There were no differences in mean summary stress scores between the mothers and fathers in the 2 preterm groups at 12 months, but the intraclass correlation coefficient was higher in the intervention group. CONCLUSIONS: This early-intervention program reduces parenting stress among both mothers and fathers of preterm infants to a level comparable to their term peers. We are now studying whether this will result in long-term beneficial effects.

Adult↗

Preterm delivery among Inuit women in the Baffin Region of the Canadian Arctic.

OBJECTIVE: To evaluate the rate and causes of preterm (before 37 weeks gestation) and very preterm (before 32 weeks gestation) delivery among a population of Inuit living in Canada. STUDY DESIGN: Three-year retrospective cross-sectional review of charts for patients delivering in the Baffin Region of Canada. RESULTS: There were 938 births over the study period; 95% to Inuit women. Inuit women had a preterm delivery rate of 18.2% and a very preterm delivery rate of 2.4%, more than twice the Canadian national average. Sociodemographic risk factors for preterm delivery including substance use, young age, single marital status, and poor nutrition, occurred more frequently among Inuit women compared to non-Inuit women, but were not independently associated with prematurity. Known medical and obstetrical risk factors were associated with preterm delivery among Inuit women; history of prior preterm delivery, multiple pregnancy, placenta previa, poor weight gain and vaginal bleeding after 20 weeks gestation. Hospitalization rates and infant mortality were higher among preterm infants. The most common indication for hospitalization was respiratory infection (51.1%) followed by other infection (15.8%). CONCLUSION: Inuit women had preterm and very preterm delivery rates more than twice the Canadian national average. Preterm delivery was associated with several medical risk factors and resulted in significant increases in infant hospitalization and mortality.

Arctic Regions↗

Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery.

OBJECTIVE: To evaluate the relationship between interleukin (IL)-18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra-amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term. DESIGN: A prospective follow up study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. SAMPLE: Women with singleton pregnancies (<34 weeks) presenting with preterm labour (n = 87) or preterm prelabour rupture of membranes (n = 47) and women, not in labour, at term (n = 28). METHODS: Amniotic fluid was retrieved transabdominally. Cervical mucus was taken from the uterine cervix of women in preterm labour and at term. IL-18 was analysed with enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: IL-18 in relation to microbial invasion of the amniotic fluid, delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. RESULTS: The levels of IL-18 in cervical mucus and amniotic fluid were higher in women with preterm labour than in those not in labour at term. In the preterm labour group, significant associations were found between elevated IL-18 in amniotic fluid and microbial invasion of the amniotic fluid, as well as between delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. Delivery was delayed longer in the preterm prelabour rupture of membranes subgroup with IL-18 >or=1.0 ng/mL than in that with IL-18 <1.0 ng/mL. CONCLUSIONS: In the preterm labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated with microbial invasion of the amniotic fluid, intra-amniotic inflammation and prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture of the membranes group correlated with a longer interval to delivery.

Adult↗

Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.

CONTEXT: Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits. OBJECTIVE: To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes. DESIGN AND SETTING: Case-control study conducted in 1998 and 1999 at 2 US university medical schools. PARTICIPANTS: A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status. MAIN OUTCOME MEASURES: Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children. RESULTS: Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P =.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P =.01]; right, 7.4% [P =.005]), and subgenual (left, 8.9% [P =.03]; right, 11.7% [P =.01]) cortices. Preterm children's brain volumes were significantly larger (by 105. 7%-271.6%) in the occipital and temporal horns of the ventricles (P<. 001 for all) and smaller in the cerebellum (6.7%; P =.02), basal ganglia (11.4%-13.8%; P</=.005), amygdala (left, 20.2% [P =.001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P =.001]; right, 12.0% [P =.007]), and corpus callosum (13.1%-35.2%; P</=.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all). CONCLUSIONS: Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.

Brain↗

Early volume expansion for prevention of morbidity and mortality in very preterm infants.

BACKGROUND: Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. OBJECTIVES: In very preterm infants, does early volume expansion reduce morbidity and mortality. If volume expansion is effective, what type of volume expansion is most effective. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. See Review Group details for more information. This was supplemented by additional searches of the Oxford Database of Perinatal Trials, and updated search performed of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library Issue 1, 2004), MEDLINE (1996-January 2004), EMBASE (1980-January 2004), previous reviews including cross references (all articles referenced), abstracts and conferences (Perinatal Society of Australia and New Zealand, and Pediatric Academic Societies and American Academy of Pediatrics meetings 1998-2003). SELECTION CRITERIA: Randomised trials of early volume expansion with normal saline, fresh frozen plasma, albumin, plasma substitutes or blood compared to no treatment or another form of volume expansion in preterm infants < 32 weeks gestation or < 1500g were included. Volume expansion was defined as at least 10 mls/kg given in the first 72 hours of life. DATA COLLECTION AND ANALYSIS: Standard methods of the Neonatal Review Group with use of relative risk (RR), risk difference (RD) and weighted mean difference (WMD). The fixed effects model using RevMan 4.1 was used for meta-analysis. Data from individual studies were only eligible for inclusion if a least 80% of infants were reported for that outcome. MAIN RESULTS: Seven studies were included. Five studies, four with data for mortality, compared volume to no treatment. Most studies enrolled very preterm infants on the basis of gestation or birthweight. Two studies comparing different types of volume expansion enrolled very preterm infants with hypotension. No study enrolled infants on the basis of low blood flow. One study examined the effect of volume expansion on blood flow but in normotensive very preterm infants. Comparing volume and no treatment, 4 studies with a total of 940 very preterm infants reported no significant difference in mortality (RR 1.11, 95% CI 0.88, 1.40). The large NNNI 1996 study reported no significant difference in severe disability (RR 0.80, 95% CI 0.52, 1.23), cerebral palsy (RR 0.76, 95% CI 0.48, 1.20) and combined death or severe disability (RR 1.00, 95% CI 0.80, 1.24). Although one small study (Beverley 1985) reported reduced P/IVH with volume expansion, this was not supported by any other study. No significant difference was reported in grade 3-4 P/IVH and combined death or grade 3-4 P/IVH. One study (NNNI 1996) reported no significant difference in the incidence of hypotension. The finding of decreased necrotising enterocolitis and increased sepsis in infants who received fresh frozen plasma compared to a gelatin-based plasma substitute or no treatment in one study should be treated with caution. No significant differences in mortality or disability were found in this study. Comparing albumin and saline in hypotensive infants, one study (Lynch 2002) reported a significant increase in mean BP and reduced incidence of treatment failure (persistent hypotension). The other study (So 1997) and the meta-analysis of the two studies found no significant difference in treatment failure (RR 0.75, 95% CI 0.53, 1.06) or in any other clinical outcome. REVIEWERS' CONCLUSIONS: There is no evidence from randomised trials to support the routine use of early volume expansion in very preterm infants without cardiovascular compromise. There is insufficient evidence to determine whether infants with cardiovascular compromise benefit from volume expansion. There is insufficient evidence to determine what type of volume expansion should be used in preterm infants (if at all) or for the use of early red cell transfusions. The significance of the finding of a significant increase in blood pressure in hypotensive preterm infants in one trial comparing albumin and saline is unclear, but the overall meta-analyses found no other significant clinical benefit in using albumin compared to saline.

Blood Volume↗

Accuracy of absence of fetal breathing movements in predicting preterm birth: a systematic review.

OBJECTIVE: To determine the accuracy with which the absence of fetal breathing movements on ultrasound examination predicts spontaneous preterm birth in women with threatened preterm labor. METHODS: Data sources included Medline, Embase, Pascal, Biosis, Cochrane Library, Medion, National Research Register, SciSearch, conference papers, and manual searching of bibliographies of known primary and review articles. A study was selected if it used absence of fetal breathing movements on ultrasound to predict spontaneous preterm birth in women with threatened preterm labor but before advanced cervical dilatation. Two reviewers independently selected studies and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables with birth within 48 h and within 7 days of testing as the reference standards. Likelihood ratios for a positive test (LR+) and negative test (LR-) were calculated as a measure of accuracy. RESULTS: There were eight studies, which included a total of 328 women, evaluating the accuracy of absence of fetal breathing movements in predicting spontaneous preterm birth in women with threatened preterm labor. There were differences in the methodological quality among the included studies. All were lacking in one or more item that make up an ideal test accuracy study. For women presenting with threatened preterm labor, meta-analysis showed a summary LR+ of 14.80 (95% CI, 6.30-34.79) with a corresponding summary LR- of 0.46 (95% CI, 0.36-0.58) for predicting preterm birth within 7 days, and summary LR+ of 7.84 (95% CI, 1.12-54.99) and summary LR- of 0.25 (95% CI, 0.13-0.48) for predicting preterm birth within 48 h of testing. CONCLUSION: Absence of fetal breathing movements has the potential to be a useful test in predicting preterm birth both within 7 days and within 48 h of testing. However, the available studies were deficient in their sample size and quality of methodology. Future research should be undertaken to evaluate this technology and to address the methodological deficiencies.

Female↗

Urinary lithogenic and inhibitory factors in preterm neonates receiving either total parenteral nutrition or milk formula.

UNLABELLED: The aim of this study was to evaluate prospectively the influence of nutrition on certain factors which may inhibit or promote nephrocalcinosis in two groups of preterm infants, receiving total parenteral nutrition (TPN) and special preterm milk formula respectively, but not furosemide. A total of 37 preterm infants, 15 on TPN and 22 fed a special preterm formula were studied at the end of the 1st, 2nd and 3rd weeks of life, at which time serum and 8 h urine specimens were collected. High ratios of urinary calcium to urinary creatinine (UCa/cr), urinary oxalate to urinary creatinine (Uox/cr) and urinary calcium to urinary citrate (UCa/cit) indicates an increased risk for nephrocalcinosis while high urinary citrate to urinary creatinine (Ucit/cr) ratio indicates protection. Uox/cr increased significantly (P<0.05) in those infants fed preterm formula, from the end of 2nd week of life and was two-fold higher than in the TPN group of preterm infants (P<0.01). Ucit/cr was higher throughout the study period in the formula fed than in the TPN preterm infants. UCa/cit was five-fold higher (P<0.01) in the TPN group, by the end of the 3rd week. Urinary calcium and magnesium was similar in both groups during the study period. Two of the infants studied (5.4%), one from each group, developed nephrocalcinosis. CONCLUSION: In preterm neonates on total parenteral nutrition, urinary oxalate -to-creatinine ratio (a potent lithogenic factor) was lower and urinary citrate -to-creatinine ratio (a lithoprotective factor) also lower than in formula fed neonates. The type of feeding (total parenteral nutrition or special preterm milk formula) seems to affect urinary oxalate and citrate but not calcium and magnesium in non-furosemide treated preterm infants during the first 3 weeks of life.

Animals↗

Measurement of bone mineral density by dual energy X-ray absorptiometry in preterm infants fed human milk or formula.

UNLABELLED: Bone mineralization of healthy preterm infants fed human milk were compared with that of similar fed preterm formula. Bone mineralization was studied by dual energy X-ray absorptiometry in 43 preterm infants divided into two groups; 21 preterm infants were fed with maternal breast milk and 22 preterm infants with a preterm formula containing 70 mg calcium and 35 mg phosphorus per decilitre. CONCLUSION: Preterm infants fed breast milk had lower bone mineral density than the preterm formula-fed group. Fortifying preterm human milk with calcium and phosphorus will improve bone mineralization in preterm infants.

Absorptiometry, Photon↗

Coitus during pregnancy is not related to bacterial vaginosis or preterm birth.

OBJECTIVE: Our goal was to assess the relationship between bacterial vaginosis and sexual intercourse and the impact of both on preterm birth. STUDY DESIGN: The presence of bacterial vaginosis was assessed in 790 healthy nulliparous women between 8 and 17 weeks' gestation, and they were then asked to record weekly the number of occasions of sexual intercourse from registration to term. The end point for each was the occurrence of preterm uterine contractions, preterm birth, or preterm rupture of the membranes. RESULTS: A total of 407 women returned the specific follow-up charts on vaginal intercourse. Bacterial vaginosis was detected at registration in 93 of the 407 subjects (22.9%), but the presence or absence of bacterial vaginosis had no predictive value as regards the frequency of subsequent intercourse. Of the 39 women (9.6%) who experienced threatened preterm labor, 16 were delivered before 37 weeks of gestation. In addition, premature rupture of membranes occurred in 48 women (9 preterm and 39 term). The 95% confidence interval for the weekly frequency of intercourse was calculated for those women delivered at term; a larger (p < 0.05) proportion of women delivered preterm, with (6/9, 66.7%) or without (13/16, 81.3%) premature rupture of membranes, had frequencies less than the 95% confidence interval during the second trimester of pregnancy; the respective proportions were 75.0% (6/8) and 78.6% (11/14) during the third trimester. Furthermore, among those women who had stopped having sexual intercourse in the last trimester, a larger (p < 0.05) proportion was delivered preterm (57.1%), with or without premature rupture of membranes, than was delivered at term (13.6%). In addition, only three women (18.8%) delivered preterm, with (two women) or without (one woman) premature rupture of membranes, reported having intercourse within 1 week before the onset of complications. CONCLUSION: For healthy nulliparous women, coitus during pregnancy is not related to bacterial vaginosis and does not predispose to preterm birth.

Coitus↗

Elevated protease activities in human amnion and chorion correlate with preterm premature rupture of membranes.

OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal membranes resulting in preterm birth remains unknown. Studies suggest that fetal membranes are susceptible to weakening by protease attack and that collagenases may be active at the site of rupture. In this study fetal membranes from women delivered after preterm premature rupture of membranes were compared with control membranes and analyzed qualitatively and quantitatively for protease activities. STUDY DESIGN: Fourteen membranes from women with preterm premature rupture of membranes and nine membranes from women delivered preterm without premature rupture of membranes or otherwise normal women delivered at term vaginally or by cesarean section were studied. Zymogram gel electrophoresis with gelatin incorporation was used to assess the number and apparent molecular weights of protease activities. Functional and quantitative studies of protease activity were measured by fluorescent substrate cleavage. RESULTS: Zymogram gel electrophoresis studies demonstrated the presence of five to seven different protease bands in preterm premature rupture of membranes samples, whereas control membranes demonstrated only one to three protease bands. Fluorescent studies of protease activity demonstrated a 10- to 40-fold increase in activity in membranes from women with preterm premature rupture of membranes compared with normal control membranes. Studies with protease inhibitors suggest that most of the activity is due to metalloproteinases. CONCLUSION: In membranes from women with preterm premature rupture of membranes there appears to be a general increase in the amount of protease activity and increased numbers of putatively different proteases. Increased activity or deregulated protease control may mediate preterm premature rupture of membranes and be a potentially remediable cause of preterm birth.

Amnion↗

A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth.

OBJECTIVE: The rarer of 2 alleles of a polymorphism in the promoter of the tumor necrosis factor alpha gene (TNF) has been associated with spontaneous preterm birth following preterm premature rupture of the fetal membranes in some populations. The aim of this study was to assess if the presence of symptomatic bacterial vaginosis amplifies the risk of spontaneous preterm birth in those with a "susceptible" TNF genotype. STUDY DESIGN: A case-control study was performed at our institution. Cases (n=125) were defined as women who delivered before 37 weeks as a result of ruptured membranes or preterm labor, while control subjects (n=250) were defined as women who delivered after 37 weeks. DNA was collected from maternal blood and analyzed for the TNF genotype. Information on symptomatic bacterial vaginosis and other risk factors for preterm birth was obtained by review of the antenatal record. Multiple logistic regression was also used to test the interaction between bacterial vaginosis, the TNF genotype, and preterm birth. RESULTS: Maternal carriers of the rarer allele (TNF-2) were at a significantly increased risk of spontaneous preterm birth [odds ratio (OR) 2.7, 95% CI 1.7-4.5]. The association between TNF-2 and preterm birth was modified by the presence of bacterial vaginosis, such that those with a "susceptible" genotype and bacterial vaginosis had increased odds of preterm birth compared with those who did not (OR 6.1, 95% CI 1.9-21.0). CONCLUSION: This study provides preliminary evidence that an interaction between genetic susceptibilities (ie, TNF-2 carriers) and environmental factors (ie, bacterial vaginosis) is associated with an increased risk of spontaneous preterm birth.

Adolescent↗

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes.

OBJECTIVE: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes. STUDY DESIGN: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. RESULTS: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03). CONCLUSIONS: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.

Adult↗

Fetal immune response to oral pathogens and risk of preterm birth.

OBJECTIVE: The purpose of this study was to determine the relationship between fetal inflammatory and immune responses to oral pathogens and risk for preterm birth. STUDY DESIGN: Six hundred and forty umbilical cord blood specimens were prospectively collected. Cord serum levels of C-reactive protein, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, Prostaglandin E2, and 8-isoprostane were determined by enzyme-linked immunosorbent assay and categorized as > median (high) versus < or = median (low). Presence of fetal immunoglobulin M (IgM) antibody against oral pathogens was determined by checkerboard immunoblot assay; detection of > or = 1 oral pathogen specific antibody was categorized as positive. Preterm birth was defined as spontaneous delivery at <35 weeks. Chi-square analysis was used to determine association between cord serum mediator or IgM category and preterm birth. Odds ratios (OR) for preterm birth were calculated, stratified by mediator and IgM category. RESULTS: Of 640 births, 48 (7.5%) delivered preterm. Preterm birth rates were higher if categorized as high versus low 8-isoprostane or TNF-alpha (23 vs 5%, P < .001 and 10 vs 4%, P < .01, respectively). Preterm birth rates were also higher if categorized as IgM positive versus negative (10.6 vs 5.8%, P = .04). The joint effects of fetal IgM seropositivity, detectable C-reactive protein, or high 8-isoprostane, PGE(2), or TNF-alpha resulted in significantly increased risk for preterm birth (adjusted OR [95% CI]: 6.0 [2.2-16.5], 4.3 [1.6-11.5], 4.1 [1.5-11.6], and 7.6 [2.3-20.8], respectively). CONCLUSION: Fetal exposure to oral pathogens evidenced by an IgM response is associated with preterm birth, and the risk for preterm birth is greatest among fetuses that also demonstrate an inflammatory response.

C-Reactive Protein↗