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Cervical ureaplasma urealyticum colonization: comparison of PCR and culture for its detection and association with preterm birth.

We developed a 16S ribosomal (r) RNA gene-based PCR assay specific for Ureaplasma urealyticum and compared it with culture. We also wanted to assess the role of cervical U. urealyticum colonization in preterm births. Cervical swabs from 100 women with preterm contractions and from 50 asymptomatic pregnant women were collected and analyzed using PCR. The PCR and culture methods were compared using the samples from the asymptomatic patients. PCR and culture were equally effective at detecting U. urealyticum. Cervical colonization correlated with preterm delivery, with rates of 71% and 37% for those delivering preterm and those with term delivery, respectively (p = 0.008). The relative risk of preterm delivery if colonized with U. urealyticum was 3.34. 16S rRNA gene-based PCR proved to be a useful tool for detecting U. urealyticum compared to culture. Lower genital tract colonization with U. urealyticum was associated with preterm birth.

Bacteriological Techniques↗

Magnesium sulfate loading: preeclampsia vs preterm labor (a clinical pearl).

OBJECTIVE: To measure the apparent volume of distribution (AVOD) for magnesium (Mg) in preeclampsia and preterm labor and determine if a standard 4 gm loading dose of magnesium sulfate (MgSO4) is sufficient to attain therapeutic levels. METHODS: Twenty-five patients with preeclampsia and 25 with preterm labor received 4 g of MgSO4 intravenously over 15 minutes. Serum Mg levels were determined before and one minute after loading and the AVOD for Mg was calculated. Stepwise linear regression with AVOD as the dependent variable was performed and comparisons between the groups were made. RESULTS: Preeclamptics were heavier, had greater surface areas, and presented at a later stage of pregnancy than did patients with preterm labor. Despite these differences AVOD did not differ between the groups. Predose magnesium levels were slightly higher in the preeclamptic group (p = .04). Post-loading levels were nearly identical due to similar AVOD's and, because of the lower levels required for seizure prevention as opposed to tocolysis, were therapeutic 88% of the time in preeclampsia but only 12% of the time in preterm labor (p < .001). Multivariate analysis revealed that only ideal body weight, degree of underweight, and current therapy with betamimetics were significantly related to AVOD. CONCLUSION: AVOD was found to be similar in preeclamptic and preterm labor patients. A 4 g loading dose of MgSO4 is usually adequate to achieve therapeutic levels in preeclampsia but not in preterm labor.

Female↗

Comparison of the phospholipid classes in human milk in Japanese mothers of term and preterm infants.

BACKGROUND: Phospholipids (PLs) play an essential role in the growth and brain development of infants. AIM: To investigate PL composition in human milk (HM), including lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine (PC) and sphingomyelin (SM), from healthy Japanese mothers. Analyses were performed on colostrum, transitional milk and mature milk from mothers of preterm and term infants. METHODS: HM samples were collected from mothers of 15 term infants (term group) and of 19 preterm infants (preterm group). PL composition was determined by two-dimensional thin-layer chromatography in conjunction with phosphorus analysis. RESULTS: In both groups, the PL content (% of total lipid) of mature milk was significantly lower than in colostrum. SM and PC were the main PLs in HM, but in the preterm group, the percentage of SM in mature milk was significantly higher and PC in mature milk was significantly lower than in the term group. CONCLUSION: The transition from colostrum to mature milk leads to an increase in SM and a decrease in PC in the HM of preterm infants, along with a decrease in PL content. This is the first report to demonstrate the differences in PL composition in HM between mothers of preterm and term infants.

Adolescent↗

New-onset hypertension in late pregnancy is associated with lower fetal and infant mortality in preterm twins.

OBJECTIVE: To assess the association between new-onset hypertension in late pregnancy (NOH) and fetal and infant mortality in early preterm, late preterm, and full-term twins. METHODS: We conducted a retrospective cohort study in 275, 316 twins in 1995-1997 based on multiple birth registration dataset of USA. Generalized estimating equations (GEEs) was used to evaluate the odds ratios (OR) of fetal and infant death (at individual level) associated with NOH, with adjustment of potential confounders at both twin set level and individual level. RESULTS: The risks for early neonatal death (OR = 0.52, 95% CI: 0.36, 0.76) and late neonatal death (OR = 0.57, 95% CI: 0.37, 0.87) were decreased in early preterm twins born to mothers with NOH compared with early preterm twins born to mothers with normal blood pressure. The decreased risks for fetal death (OR = 0.40, 95% CI: 0.30, 0.53; OR = 0.46, 95% CI: 0.53, 0.65) and infant death (OR = 0.35, 95% CI: 0.28, 0.44; OR = 0.68, 95% CI: 0.51, 0.91) were associated with NOH in both early and late preterm twins, whereas no association between NOH and fetal/infant mortality were observed in full-term twins. CONCLUSION: NOH is associated with lower risk of fetal death and infant death in preterm twins.

Adult↗

The effect of treating bacterial vaginosis on preterm labor.

OBJECTIVE: Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II-II. METHODS: We searched for all of the studies from the years 1994 to 2001 via Medline's database, including MD Consult and Ovid Mednet. RESULTS: Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. CONCLUSIONS: Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated.

Adult↗

Language abilities of 8-year-old preterm children among the northern Finland 1-year birth cohort for 1985-1986.

The language abilities of 42 8-year-old preterm children with birth weight < 1,750 g from a 1-year birth cohort in northern Finland was studied with four different language tests. Control children from the same birth cohort matched individually with their preterm pairs for age, sex, twinship, mother's education, place of residence, birth order and family type were also studied. In psycholinguistic test, auditory skills did not differ between the preterm and the full-term groups. Nor did any other linguistic subtest differentiate between the groups. Instead, the preterm children scored significantly poorer than their controls in visual subtests. The study also showed that the poor performance in visual tests was associated with neonatal morbidity, namely neonatal infections, need for continuous positive airway pressure (CPAP) treatment and patent ductus arteriosus (PDA). When studying the language abilities of preterm children, we suggest that qualitative methods should be used to analyse linguistic skills. We recommend versatile follow-up of preterm children until school age.

Catchment Area, Health↗

Cervical assessment in women with threatened preterm labor.

OBJECTIVE: The aim of the study was to examine the clinical value of cervical assessment by transvaginal ultrasonography in women with symptoms of preterm labor. METHODS: We prospectively evaluated 172 women with singleton pregnancies and symptoms of preterm labor. Seventy of them were nulliparas, while 102 were multiparas. Gestational age ranged between 24 and 34 wks. All women underwent cervical assessment with transvaginal ultrasonography and were given intravenous tocolytics. The only parameter evaluated was cervical length. Women with multiple pregnancies, gestational age <24 wks or >34 wks, cervical dilatation >2 cm, placenta praevia, premature rupture of membranes, or cervical cerclage were excluded from the study. The outcome measure was delivery before 34 wks gestation. RESULTS: The preterm delivery rate before 34 wks was 37%. The sensitivity and the specificity of a cervical length of less than 20 mm was 60 and 53.8% and 97.7 and 95.2% for nulliparas and multiparas, respectively. A cervical length <20 mm was also 93.7% predictive of preterm delivery in nulliparas and 87.5% in multiparas, while the corresponding numbers for its negative predictive value (NPV) were 81.4 and 76.9%, respectively. CONCLUSIONS: Cervical assessment in women with symptoms of preterm labor can distinguish those at high risk for preterm delivery. Cervical sonography can be a valuable adjunct to the clinical evaluation of these patients.

Adult↗

Strategies for prevention of feed intolerance in preterm neonates: a systematic review.

Postnatal growth restriction and failure to thrive have been recently identified as a major issue in preterm, especially extremely-low-birth-weight neonates. An increased length of time to reach full enteral feedings is also significantly associated with a poorer mental outcome in preterm neonates at 24 months corrected age. Optimization of enteral nutrition without increasing the risk of necrotizing enterocolitis (NEC) has thus become a priority in preterm neonates. A range of feeding strategies currently exists for preventing/minimizing feed intolerance in preterm neonates reflecting the dilemma surrounding the definition and significance of signs of feed intolerance due to ileus of prematurity and the fear of NEC. The results of a systematic review of current strategies for preventing/minimizing feed intolerance in preterm neonates are discussed. The need for clinical research in the area of signs of feed intolerance is emphasized to develop a scientific basis to feeding strategies. Only large pragmatic trials based on such strategies will reveal whether the benefits (improved growth and long term neurodevelopmental outcomes) of aggressive enteral nutrition can outweigh the risks of a potentially devastating illness like NEC, and of prolonged parenteral nutrition in preterm neonates.

Enteral Nutrition↗

Maternal intravascular inflammation in preterm premature rupture of membranes.

OBJECTIVE: Intrauterine inflammation has been implicated in the mechanisms responsible for preterm premature rupture of membranes (PROM). However, it is unclear whether this inflammatory process remains localized to the uterus, at the site of membrane rupture, or extends to the maternal compartment. Flow cytometric analysis is a sensitive method to assess the presence and magnitude of in vivo inflammation. This study was conducted to determine whether preterm PROM is associated with changes in the phenotypic and metabolic characteristics of maternal granulocytes and monocytes consistent with the presence of maternal intravascular inflammation. STUDY DESIGN: A prospective cross-sectional study was performed including patients with preterm PROM (n = 43) and normal pregnancy (n = 51). Maternal intravascular inflammation was studied using flow cytometry. Maternal blood was assayed to determine granulocyte and monocyte phenotype using monoclonal antibodies, which included cluster differentiation (CD) markers CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b and human leukocyte antigen (HLA)-DR. The quantities of basal intracellular reactive oxygen species (iROS) and oxidative burst was assessed. Statistical analysis was conducted with the use of non-parametric methods. A p value < 0.01 was considered significant. RESULTS: Preterm PROM was associated with a significant increase in the median mean channel brightness (MCB) of CD11b, CD14, CD64 and CD66b on granulocytes and median MCB of CD11b on monocytes. The oxidative burst and the stimulation index in both cell types were higher in preterm PROM than in normal pregnancy (p < 0.01). CONCLUSION: Preterm PROM is associated with phenotypic and metabolic changes in circulating granulocytes and monocytes.

Adolescent↗

Frequency of eating during pregnancy and its effect on preterm delivery.

Frequency of eating or meal patterns during pregnancy may be a component of maternal nutrition relevant to pregnancy outcome. To identify meal patterns of pregnant women and investigate the relation between these meal patterns and preterm delivery, the authors performed an analysis using data from the Pregnancy, Infection, and Nutrition Study (n = 2,065). Women recruited from August 1995 to December 1998 were categorized by meal patterns on the basis of their reported number of meals (breakfast, lunch, and dinner) and snacks consumed per day during the second trimester. An optimal pattern was defined according to the Institute of Medicine recommendation of three meals and two or more snacks per day. In this population, 72 percent of the women met this recommendation, and 235 delivered preterm. Women who consumed meals/snacks less frequently were slightly heavier prior to pregnancy, were older, and had a lower total energy intake. In addition, these women had a higher risk of delivering preterm (adjusted odds ratio = 1.30, 95 percent confidence interval: 0.96, 1.76). There was no meaningful difference in the risk by early versus late preterm delivery, but those who delivered after premature rupture of the membranes (adjusted odds ratio = 1.87, 95 percent confidence interval: 1.02, 3.43) had a higher risk than those who delivered after preterm labor (adjusted odds ratio = 1.11, 95 percent confidence interval: 0.64, 1.89). This study supports previous animal model work of an association between decreased frequency of eating and preterm delivery.

Adolescent↗

Rates of preterm delivery among Black women and White women in the United States over two decades: an age-period-cohort analysis.

The authors assessed the influence of age, period, and cohort effects on rates of preterm delivery in the United States. Rates of preterm delivery for singleton births (<37 weeks) in seven age groups (15-19, 20-24,., 45-49 years), five periods (1975, 1980, 1985, 1990, 1995), and 11 maternal birth cohorts (1926-1930, 1931-1935,., 1976-1980) were examined. Over the 20-year study interval, preterm delivery increased by 3.6% among Blacks (from 15.5% in 1975 to 16.0% in 1995) and by 22.3% among Whites (from 6.9% to 8.4%). Among Black primigravid women, rates of preterm delivery increased from 1975 to 1990 and began to decline thereafter; among Whites, the rates increased between 1975 and 1995. In Blacks, women aged 25-29 years had the lowest rates for the first and second births, and women aged 30-34 years had the lowest rate for subsequent births. In Whites, the age groups with the lowest preterm delivery rates were 20-24 years for first births and 25-29 years for subsequent births. Cohort-specific rates of preterm delivery remained fairly constant across age strata and periods for Whites, but a small trend was apparent for Blacks aged 30-44 years. The consistency of the observed age effects across periods and cohorts suggests that the age effect is partly due to biologic factors. The presence of period effects might be linked to the increased survival of premature infants or to increased viability among births occurring at lower lengths of gestation.

Adolescent↗

Exploration of threshold analysis in the relation between stressful life events and preterm delivery.

Biologic evidence suggests that the hormones activated by stress affect gestational length, but the results of epidemiologic investigations are inconsistent. The authors of this paper know of no threshold models that have been studied; these models assume that stress does not affect preterm delivery until a certain amount of stress has been experienced but that each unit of stress above the threshold adds to the risk of preterm delivery. By using standard logistic regression, the authors compared threshold and nonthreshold models of the relation between number of stressful life events and preterm delivery in 11 US states. They used data on 1990-1995 births from the Pregnancy Risk Assessment Monitoring System. The risk of preterm delivery among multiparas who gave birth in 1990-1993 increased 7% for each event over five they experienced, but no relation was found for 1994-1995 births. Among primiparas who gave birth in 1994-1995, the risk increased 5% for each event over two, but no relation was found for 1990-1993 births. These results suggest that a threshold model may fit the relation between stress and preterm delivery better than one with no threshold. However, the inconsistent results are difficult to reconcile with a biologic threshold in the relation between stress and preterm delivery.

Adult↗

Maternal prenatal depressive symptoms and spontaneous preterm births among African-American women in Baltimore, Maryland.

The purpose of this study was to examine the relation between maternal depressive symptoms and spontaneous preterm birth. From 1991 to 1993, pregnant, African-American women were prospectively enrolled at four hospital-based clinics in Baltimore, Maryland, that serve low-income areas of the city. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to assess depressive symptoms. Multiple logistic regression analysis estimated the independent contribution of maternal depressive symptoms to spontaneous preterm birth, controlling for behavioral, clinical, and demographic variables. Among the 1,399 women in the sample, 117 (8.4%) had a spontaneous preterm delivery. Spontaneous preterm birth occurred among 12.7% of those with a CES-D score in the upper 10th percentile and among 8.0% of those with a lower score (relative risk = 1.59). The adjusted odds ratio for an elevated CES-D score was 1.96 (95% confidence interval: 1.04, 3.72); hence, maternal depressive symptoms in this sample of African-American women were independently associated with spontaneous preterm birth. Effective treatment of depression in pregnant women could ultimately result in a reduction of spontaneous preterm births.

Adult↗

The probability of giving birth among women who were born preterm or with impaired fetal growth: a Swedish population-based registry study.

The primary aim of this study was to investigate whether women born prematurely or with impaired fetal growth have a reduced probability of giving birth. Using Swedish population-based registries, the authors identified 148,281 women born in 1973-1975 for follow-up until 2001. Of these women, 4.1% were born preterm and 0.32% very preterm, 0.29% were born with a very low birth weight, and 5.4% were small for gestational age. Outcome measures were the hazard ratios for giving birth during the study period. Adjustments were made for socioeconomic factors. Very-low-birth-weight women displayed a reduced probability of giving birth (hazard ratio = 0.74, 95% confidence interval: 0.60, 0.91), most apparent among women aged 25 or more years. There were also tendencies of reduced hazard ratios of giving birth among women born preterm or very preterm in this age interval. Women born small for gestational age (below -2 standard deviations) seemed to be more likely to have given birth (hazard ratio = 1.09, 95% confidence interval: 1.04, 1.14), but when a more extreme group of small-for-gestational-age women (below -3 standard deviations) was defined, the association was less evident (hazard ratio = 1.04, 95% confidence interval: 0.94, 1.16). The results suggest that very-low-birth-weight women and, possibly, women born preterm or very preterm have a reduced probability of giving birth, while the results regarding small for gestational age are less clear.

Adult↗

Plasma C-reactive protein in early pregnancy and preterm delivery.

Systemic maternal infections have been associated with preterm delivery. The authors examined the association of C-reactive protein (CRP), a marker of inflammation, with preterm delivery. This nested case-control study was conducted within Project Viva in Massachusetts between 1999 and 2002. Subjects were 117 women who delivered preterm (< 37 weeks' gestation) and 117 controls (term deliveries) matched on age, race/ethnicity, and smoking status. High-sensitivity CRP assays were performed on early-pregnancy (5.3-19.3 weeks' gestation) plasma samples. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression adjusted for matching factors, gestational age at blood collection, and prepregnancy body mass index. Median concentration of CRP was 3.2 mg/liter in cases versus 2.4 mg/liter in controls. No significant association was found between quartiles of CRP and preterm delivery. However, CRP levels exceeding the threshold defined in the literature were associated with increased risk of preterm delivery (odds ratio = 2.55, 95% confidence interval: 1.05, 6.02 for CRP > or = 8 mg/liter). The association was stronger among cases who experienced spontaneous delivery (odds ratio = 4.64, 95% confidence interval: 0.94, 22.96) versus indicated delivery (odds ratio = 1.42, 95% confidence interval: 0.44, 4.61). These findings suggest that very high CRP levels in early pregnancy are associated with preterm delivery.

Alcohol Drinking↗

Object working memory deficits predicted by early brain injury and development in the preterm infant.

Children born preterm and of very low birth weight are at increased risk of learning difficulties and educational under-achievement. However, little is known about the specific neuropsychological problems facing these children or their neurological basis. Using prospective longitudinal data from a regional cohort of 92 preterm and 103 full-term children, this study examined relations between term MRI measures of cerebral injury and structural brain development and children's subsequent performance on an object working memory task at the age of 2 years. Results revealed clear between-group differences, with preterm children having greater difficulty encoding new information in working memory than term control children. Within the preterm group, task performance at the age of 2 years was related to both qualitative MRI measures of white matter (WM) injury and quantitative measures of total and regional brain volumes assessed at term equivalent. Bilateral reductions in total tissue volumes (%region) of the following cerebral regions were specifically related to subsequent working memory performance: dorsolateral prefrontal cortex, sensorimotor, parietooccipital and premotor. Associations between total cerebral tissue volumes at term (adjusted and unadjusted for intracranial volume) persisted even after the effects of WM injury were taken into account. This suggests that early disturbance in cerebral development may have an independent adverse impact on later working memory function in the preterm infant. These findings add to our understanding of the neuropathological pathways associated with later executive dysfunction in the very preterm infant.

Brain↗

Inhibition of nitric oxide synthesis causes preterm delivery in the mouse.

The aim of the present study was to investigate whether an inhibitor of nitric oxide (NO) synthesis provokes preterm delivery in a mouse model. ICR (CD-1) mice were injected s.c. with N(G)-nitro-L-arginine methyl esther (L-NAME) at 0, 40, 70 or 100 mg/kg on gestation day (GD) 15.5 and 16. Delivery was considered preterm if it occurred before GD 18. In a satellite study, the potential ability of the NO donor sodium nitroprusside (SNP) to prevent L-NAME-induced preterm delivery was tested. Five hours before the initiation of treatment regimen with L-NAME at 70 mg/kg, mice were implanted s.c. with micro-osmotic pumps infusing SNP at 0 or 10 microg/kg/min continuously for 3 days. Administration of L-NAME evoked preterm delivery. This response was noted in 64 and 60% of animals treated with 70 and 100 mg/kg L-NAME respectively (P < 0.05 versus control value). Infusion with SNP provided complete and significant (P < 0. 05 versus positive control value) protection from L-NAME-initiated preterm delivery. This is the first report to reveal that an inhibitor of NO synthesis initiates preterm delivery in a mouse model.

Animals↗

The effect of various infertility treatments on the risk of preterm birth.

BACKGROUND: The high incidence of preterm birth (<37 weeks gestation) is a major concern in assisted reproductive technology. The objective of this study was to compare the risk of preterm birth from singleton pregnancies following either low technology treatment (intrauterine insemination and donor insemination) or high technology treatment (IVF, ICSI and gamete intra-Fallopian transfer) with that of naturally conceived pregnancies. METHODS: Three cohorts of pregnancies resulting from either low or high technology treatment or from natural conception were included in the study. A number of potential risk factors were adjusted for. RESULTS: The incidence of very preterm birth (<32 weeks of gestation) was not significantly increased in the low technology treatment group (1.0 versus 1.3% in controls) but was significantly higher in the high technology treatment group (5.2%, P < 0.001). In spontaneous, elective Caesarean section (CS) and induced delivery onset, the risk of preterm birth increased gradually from the controls to the low technology treatment group to the high technology treatment group, while for an emergency CS the risk of preterm birth was very high in both treatment groups. CONCLUSIONS: The overall incidence of preterm birth increased significantly from the controls to the low technology treatment group and to the high technology treatment group. Logistic regression analysis showed that younger and older age, previous perinatal death and emergency CS were associated with an increased risk, while a previous live birth reduced the risk. The length of the infertile period did not seem to affect the risk in any of the treatment groups.

Cesarean Section↗