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Comparison of an improved AFP kit with the intra-amniotic PSP dye-injection method in equivocal cases of preterm premature rupture of the fetal membranes.

OBJECTIVE: We developed an improved AFP kit for detecting AFP in leaked amniotic fluid. We studied the relationship between the results of the improved AFP kit and those of the intra-amniotic PSP dye-injection test (PSP test), and compared the results of two tests with the prognosis for subsequent pregnancy outcome, in order to know the diagnostic value of the two tests for preterm PROM, especially in equivocal cases. METHODS: We compared the results of the AFP kit test with those of the PSP test in 8 equivocal cases of preterm PROM (18th to 34th weeks of gestation). RESULTS: The results of the AFP kit test coincided with those of the PSP test in all 8 equivocal cases of preterm PROM. The 4 cases that tested positive resulted in preterm deliveries; and the other 4 cases that tested negative resulted in full-term deliveries. CONCLUSION: The use of the AFP kit test is useful in assessing the prognosis for subsequent pregnancy in equivocal cases of preterm PROM. The rapid and accurate AFP kit test for diagnosing preterm PROM can be substituted for the PSP test in bedside and outpatient-clinic assessments.

Adult↗

Changes in serum levels of heat shock protein 70 in preterm delivery and pre-eclampsia.

AIM: The aim of this study was to investigate heat-shock protein (Hsp)70 as a novel marker to evaluate the curative effects of treatment for preterm delivery high-risk patients and pre-eclampsia. METHODS: After obtaining informed consent, serum samples were collected from 31 preterm delivery high-risk patients with a tocolysis index of three points or above (A), seven pre-eclampsia patients (P), 46 normal pregnant women (B), and seven non-pregnant women (C). Of the 31 preterm delivery high-risk patients, 15 had preterm delivery (Ap) and 16 had full-term delivery (Af). The levels of Hsp70 were measured using enzyme-linked immunosorbent assay. RESULTS: The Hsp70 levels in normal pregnant women were 8.6 +/- 1.9 ng/mL (first trimester), 5.5 +/- 1.0 ng/mL (second trimester) and 5.5 +/- 0.7 ng/mL (third trimester). There was no statistical difference in the Hsp70 levels between the three trimesters. The mean Hsp70 levels were 21.9 +/- 5.3 ng/mL (A), 35.3 +/- 9.6 ng/mL (Ap), 9.4 +/- 2.2 ng/mL (Af), 24.4 +/- 3.6 ng/mL (P), 6.1 +/- 0.6 ng/mL (B), and 2.4 +/- 0.6 ng/mL (C). Group Ap had significantly higher Hsp70 levels than group Af (P = 0.0112) and group B (P <0.0001). The duration of pregnancy after hospitalization for group Ap was significantly shorter than that for group Af (P=0.0088) and group B (P <0.0001). Group P also had significantly higher Hsp70 levels than group B (P <0.0001). CONCLUSION: Because Hsp70 levels were particularly high in treatment-resistant preterm delivery cases, Hsp70 may prove to be a useful marker for evaluating the curative effects of treatment for preterm delivery.

Adult↗

Cervical Ureaplasma urealyticum colonization might be associated with increased incidence of preterm delivery in pregnant women without prophlogistic microorganisms on routine examination.

AIM: We examined whether the detection of Ureaplasma urealyticum DNA in the cervix is associated with preterm labor and delivery. METHODS: Eighty-two women (23 preterm labor cases and 59 controls) with no evidence of prophlogistic microorganisms on routine microbiologic examination were enrolled for this study. U. urealyticum colonization was examined using polymerase chain reaction of cervical swabs. RESULTS: The positivity rate of U. urealyticum DNA in preterm labor cases was significantly higher than that in the controls (87.0%vs 45.8%, P=0.0007). Women in the U. urealyticum-positive group more frequently delivered preterm compared with those in the negative group (36.2%vs 11.4%, P=0.0111). In five cases that delivered preterm with histologically confirmed chorioamnionitis, U. urealyticum DNA was detected in the placenta. CONCLUSIONS: Cervical U. urealyticum colonization might be associated with preterm labor and delivery.

Adolescent↗

Risk factors for preterm, low birth weight and small for gestational age birth in urban Aboriginal and Torres Strait Islander women in Townsville.

OBJECTIVES: To assess the characteristics of Indigenous births and to examine the risk factors for preterm (<37 weeks), low birth weight (<2,500 g) and small for gestational age (SGA) births in a remote urban setting. DESIGN: Prospective cohort of singleton births to women attending Townsville Aboriginal and Islander Health Services (TAIHS) for shared antenatal care between 1 January 2000 and 31 December 2003. MAIN OUTCOME MEASURES: Demographic, obstetric, and antenatal care characteristics are described. Risk factors for preterm birth, low birth weight and SGA births are assessed. RESULTS: The mean age of the mothers was 25.0 years (95% CI 24.5-25.5), 15.8% reported hazardous or harmful alcohol use, 15.1% domestic violence, 30% had an inter-pregnancy interval of less than 12 months and 9.2% an unwanted pregnancy. The prevalence of infection was 50.2%. Predictors of preterm birth were a previous preterm birth, low body mass index (BMI) and inadequate antenatal care, with the subgroup at greatest risk of preterm birth being women with a previous preterm birth and infection in the current pregnancy. Predictors of a low birth weight birth were a previous stillbirth, low BMI and an interaction of urine infection and non-Townsville residence; predictors of an SGA birth were tobacco use, pregnancy-induced hypertension and interaction of urine infection and harmful alcohol use. CONCLUSION: The prevalence of demographic and clinical risk factors is high in this group of urban Indigenous women. Strategies addressing potentially modifiable risk factors should be an important focus of antenatal care delivery to Indigenous women and may represent an opportunity to improve perinatal outcome in Indigenous communities in Australia.

Adult↗

Failure to thrive in the term and preterm infants of mothers depressed in the postnatal period: a population-based birth cohort study.

AIMS: To examine the relationship between failure to thrive in preterm and term infants and postnatal depression in their mothers. METHOD: In a whole population birth cohort of 12,391 infants (excluding those born after term or with major congenital abnormalities) failure to thrive over the first nine months was identified using a conditional weight gain criterion which identified the slowest-gaining 5%. Depression symptoms were recorded using the Edinburgh Postnatal Depression Scale (EPDS) at 18 and 32 weeks of pregnancy and at 8 weeks and 8 months after delivery. RESULTS: After the birth, high depression scores were significantly more common in the mothers of infants born preterm, and controlling for depression scores in pregnancy did not eliminate this association after the birth. Failure to thrive was identified in 4.5% of the children born at term (531/11718) and in 8.3% of those born preterm (56/673). The difference was highly significant (chi2 = 20.25 with 1 df, p < .0001). Using a conventional cut-off on the EPDS (score > 12) to identify mothers as 'depressed', the prevalence of failure to thrive in the term infants of mothers depressed at 8 weeks postpartum was 5.0%; in the remainder of the population (controls) it was 4.3%. In mothers depressed at 8 months the prevalence was 4.3% in both groups. The prevalence of failure to thrive in the preterm infants of mothers depressed at 8 weeks was 8.8% (7.0% in controls) and in those depressed at 8 months it was 12.3% (6.7% in controls). None of these differences in prevalence was statistically significant, and significant differences did not emerge from further analyses using more stringent criteria for depression. CONCLUSIONS: Preterm births are specifically associated with high maternal depression scores in the postpartum period, and with a higher prevalence of failure to thrive. High depression scores in the postpartum period are not themselves associated with a higher prevalence of failure to thrive, however, either in infants born at term or in those born preterm.

Adult↗

Behavioural changes and bioelectric brain maturation of preterm and fullterm newborn infants: a polygraphic study.

Fifty-two preterm and fullterm infants requiring assisted ventilation were observed and examined polygraphically. In addition, 24 preterm infants without prenatal or perinatal complications and not needing assisted ventilation were examined polygraphically in order to validate a special method of differentiating sleep states and sleep cycles. State criteria were EEG records, eye movements and gross body movements. Using this evaluation method, all 14 low-risk preterm infants showed stable sleep states and cycles, as did 16 of 23 high-risk preterm and 10 of 15 high-risk fullterm infants. 11 high-risk preterm and fullterm infants were found to have extremely unstable sleep states, or were comatose. The EEG could not be evaluated in only one case. Infants requiring assisted ventilation showed the following changes in comparison with the infants who did not need ventilation: the percentage of quiet sleep increased significantly; the percentage of indeterminate sleep increased as a sign of more unstable behaviour; and the individual measurements of the recorded and observed variables showed wider variability. Bioelectric brain maturation decreased significantly with increasing risk among both preterm and fullterm infants given assisted ventilation.

Behavior↗

Use of chronological and adjusted ages to compare motor development of healthy preterm and fullterm infants.

To investigate the influence of gestational age at birth on motor development in infancy and the practice of basing motor assessments of preterm infants on an adjusted age, 21 healthy preterm and 23 fullterm infants were administered the Peabody Developmental Motor Scales at 12, 15 and 18 months of age. When quotients were based on chronological age, both the mean gross-motor and fine-motor developmental quotients of the fullterm group were significantly higher than those of the preterm group, indicating that the fullterm group had higher levels of motor development. However, when the quotients of the preterm group were based on adjusted age, which accounted for gestational age at birth, the motor quotients of the two groups did not differ significantly. It seems that motor development of healthy preterm and fullterm infants differs primarily as a function of gestational age at birth, which supports maturational theory and the practice of making age adjustments when evaluating motor development of preterm infants.

Female↗

Baseline respiratory sinus arrhythmia and heart rate responses during sustained visual attention in preterm infants from 3 to 6 months of age.

Three groups of preterm infants were studied longitudinally at 14, 20, and 26 weeks of age (corrected for gestational age). The groups included infants with no perinatal medical complications, those with mild respiratory problems requiring ventilatory assistance, and those with respiratory distress syndrome. Baseline heart rate and respiratory sinus arrhythmia (RSA) were recorded for 5 min, and heart rate was also recorded while the infants engaged in sustained visual attention to stimuli presented on video monitors. The heart rate response during stimulus orienting and sustained attention was smaller in those infants with respiratory distress syndrome than in the other preterm infants and in comparison with the response seen in full-term infants in previous research. Magnitude of RSA was positively correlated with the attention responses irrespective of the preterm group assignment. There was greater stability in baseline heart rate and RSA for the preterm infants than has been found with full-term infants. These data suggest that the cardiorespiratory functioning of the preterm infant indexes a stable individual difference characteristic that is correlated with heart responses during sustained attention, and heart rate attention systems may be damaged in the high-risk preterm infant.

Age Factors↗

Randomized controlled trial of antenatal social support to prevent preterm birth.

OBJECTIVE: To test the effect of a programme of additional antenatal social support on the occurrence of preterm birth (a birth from 20 to 36 weeks gestation) in women at risk of preterm birth. DESIGN: A prospective randomized controlled trial. The design was one of randomization before consent for a new treatment. SETTING: Three public hospital antenatal clinics in Perth and the offices of 87 obstetricians and general practitioners in Western Australia. SUBJECTS: 1970 pregnant women with poor obstetric histories entered the trial; 983 of these were randomly allocated to the programme group and 987 to the control group. INTERVENTIONS: Normal antenatal care was provided for both groups. In addition, members of the programme group were offered an intervention aimed at providing expressive (emotional) social support, consisting of antenatal home visits and telephone calls by midwives. Of the women allocated to the programme group, 24 refused consent and 69 were not traced before completion of their pregnancies, the remaining 890 women (90.5%) agreed to enter the programme, and each received at least one intervention. MAIN OUTCOME MEASURES: Gestational age at completion of the pregnancy. A pregnancy ending before 20 weeks was labelled a miscarriage. RESULTS: There were 126/981 (12.8%) preterm births in the programme group and 147/986 (14.9%) in the control group. The outcome data for two women in the programme group and one in the control group could not be found. The unadjusted odds ratio for preterm birth in the programme was 0.84 (95% CI 0.65-1.09). The observed relative reduction in preterm births associated with the programme was 13.8% (95% CI -8.2% to +31.5%) and the trial had a 60% power to exclude a true relative reduction of 25%. CONCLUSIONS: The results of this trial and those of other controlled clinical trials provide little evidence for the effectiveness of social support interventions in the prevention of preterm birth in women with poor obstetric histories.

Female↗

Levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in pregnancy with preterm delivery.

OBJECTIVE: To investigate the relationship between preterm delivery and maternal serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) levels. DESIGN: A study over a 12 month period in which all samples were collected according to a pre-set protocol. SETTING: St. Bartholomew's Hospital, London. SUBJECTS: Thirty-eight nonpregnant adult females, 456 pregnant women at various gestational ages, 84 women with average-for-gestational-age babies at term delivery, and 49 pregnant women with preterm delivery (44 with singleton pregnancy and five with twin pregnancy). MAIN OUTCOME MEASURES: Serum IGF-I and IGFBP-1 levels were determined by radioimmunoassay. RESULTS: Serum IGF-I concentrations increased as pregnancy progressed. In the third trimester, serum IGF-I levels in singleton preterm deliveries were lower than those in normal pregnancies, and IGFBP-1 concentrations were higher than those in normal pregnancies. This phenomenon was not obvious in the second trimester. Maternal circulating IGFBP-1 levels were correlated inversely with birthweight in women with singleton preterm delivery. CONCLUSIONS: Neither IGF-I nor IGFBP-1 appears to play a significant role in preterm delivery since maternal serum IGF-I and IGFBP-1 levels are similar in preterm and term deliveries.

Birth Weight↗

Previous pregnancy outcomes and subsequent risk of preterm rupture of amniotic sac membranes.

OBJECTIVE: To test the hypothesis that previous unfavourable pregnancy outcomes increase the risk for premature birth, with (PP) or without (PTB) premature rupture of the amniotic sac (PROM) at the index pregnancy and that multiple undesirable outcomes increase risk. DESIGN: Case control study. SETTING: Two university hospitals. SUBJECTS: Four hundred sixty-three women aged 15 to 45 years who were delivered preterm PROM, full term PROM and preterm without PROM matched with 463 women who delivered full term. All women included in the study had at least one previous pregnancy. OUTCOME MEASURES: Odds ratio of previous adverse pregnancy outcome among index cases. RESULTS: Compared with controls, PP cases had odds ratios of 95 for previous preterm birth, 186 for abortion and prematurity and 158 for fetal loss, abortion/prematurity after controlling for confounding variables. Compared with controls, PTB cases had an odds ratio of 96.5 for previous preterm delivery, 84 for abortion and prematurity, and 320 for fetal loss/abortion and prematurity after controlling for confounding variables. CONCLUSIONS: Previous preterm delivery, abortion and prematurity and fetal loss/abortion and prematurity all increase risk for subsequent preterm birth with or without PROM.

Abortion, Spontaneous↗

Risk of preterm delivery in pregnant women with group B streptococcal urinary infections or urinary antibodies to group B streptococcal and E. coli antigens.

OBJECTIVE: To establish whether there is an association between preterm delivery and either group B streptococcal urinary infection or the presence of urinary antibodies to group B streptococcal or E. coli antigens. DESIGN: A prospective study with urine culture and antibody measurement performed at the first antenatal visit and at 28 weeks gestation. SETTING: Ninewells Hospital, Dundee. SUBJECTS: Two thousand and forty-three women registering consecutively at an antenatal clinic. MAIN OUTCOME MEASURE: Delivery at less than 37 weeks gestation. RESULTS: No increase in preterm delivery was observed in women with positive urine cultures for group B streptococci either at booking or at 28 weeks, even when confirmed by positive repeat cultures. Preterm delivery was more common in women with elevated urinary antibodies to E. coli antigens at booking (relative risk 1.81, 95% CI 1.22-2.68, P = 0.005) and at 28 weeks (relative risk 2.36, 95% CI 1.60-3.48, P < 0.0001) and to group B streptococcal antigens at 28 weeks (relative risk 2.24, 95% CI 1.46-3.43, P = 0.0003). CONCLUSIONS: These data do not support previous reports that positive urine cultures for group B streptococci are associated with an increased risk of preterm delivery. Our report of an association between elevated levels of urinary antibodies and preterm delivery is a new finding consistent with the possibility that a local inflammatory response to uro-genital infection may be important in stimulating the onset of preterm labour. The results suggest that screening for urinary antibodies at 28 weeks gestation might help to identify a group of women at increased risk of prematurity.

Adult↗

Transabdominal cervicoisthmic cerclage in the management of recurrent second trimester miscarriage and preterm delivery.

OBJECTIVE: To evaluate the role of transabdominal cervicoisthmic cerclage (TCC) in the management of recurrent mid-trimester pregnancy miscarriage and preterm delivery. DESIGN: An observational study of 50 women with history of recurrent second trimester miscarriage and preterm delivery in whom TCC was performed. SETTING: A tertiary referral centre for high risk obstetrics. RESULTS: TCC was performed on 51 occasions in 50 women. One had TCC performed in two successive pregnancies. Prior to the procedure, they had experienced 36 first trimester miscarriages and 163 later pregnancy losses. These included 152 midtrimester miscarriages and 11 neonatal deaths after preterm delivery. There had been 4 survivors after preterm delivery. The total number of pregnancies after TCC was 61 with three women losing one pregnancy and subsequently having a successful pregnancy. Of these women 44 now have had a successful outcome. Six have not had a successful outcome. Eight women have had two successful consecutive pregnancies after TCC. The fetal survival was 85.2% post-procedure. CONCLUSIONS: TCC is a procedure that may be used in a highly selected group of women with anatomical defects of the cervix and previous failed transvaginal cerclage resulting in recurrent second trimester pregnancy loss and preterm birth. Strict selection criteria were applied as TCC is an invasive procedure. Although TCC is not widely used our study suggests it may be the procedure to consider in women who have had recurrent second trimester pregnancy losses and preterm births associated with cervical damage.

Abortion, Habitual↗

Detection of fetal fibronectin as a predictor of preterm delivery in high risk asymptomatic pregnancies.

OBJECTIVE: The study was designed to determine whether fetal fibronectin would predict delivery before 37 weeks in women at high risk of preterm delivery. STUDY METHODS: Forty-three women considered at risk of preterm delivery were recruited antenatally into a blind longitudinal study. Quantitative assays of fetal fibronectin were obtained from sequential high vaginal swabs taken fortnightly from 24 to 34 weeks of gestation. Fibronectin concentrations of 0.05 microgram/ml or more were considered as positive. RESULTS: Results were calculated by swab and by subject. The sensitivity of an individual fibronectin swab in predicting preterm delivery within 14 days of testing was 71% and the specificity was 93%. The overall positive predictive value was 31% and the negative predictive value was 99%. The sensitivity of the fibronectin swab in predicting delivery before 37 weeks was 17% and the specificity was 93%. The positive predictive value was 50% and the negative predictive value was 73%. For a woman who has had a positive swab the sensitivity in predicting preterm delivery within 14 days of testing was 80% and the specificity was 83%; a woman was counted as positive only if the final swab was positive and preceded delivery by not more than 14 days. The positive predictive value was 36% and the negative predictive value was 97%. For a woman who has had a positive swab the sensitivity in predicting delivery before 37 weeks was 54%. The specificity, the positive predictive value and the negative predictive value were 85%, 64% and 79%, respectively. Women were counted as positive if any swab in the sampling sequence was positive. Fibronectin swabbing when calculated by patient did predict preterm delivery within 14 days of testing (P=0.01) and before 37 weeks (P=0.01). Analysis of the accuracy of predicting delivery from 7 to 28 days after sampling revealed that the best prediction for delivery was within the following 14 days. CONCLUSION: Serial fetal fibronectin assessment from 24 to 34 weeks of gestation anticipated preterm delivery within 14 days of testing and before 37 weeks for high risk asymptomatic women. Such testing should be performed every two weeks.

Adult↗

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. CONCLUSIONS: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Adult↗

24 hour rhythm to the onset of preterm labour.

UNLABELLED: OBJECTIVE To describe the time of onset of contractions which result in preterm delivery to investigate if there is a diurnal influence. DESIGN: The admission register for the neonatal unit was used to identify admissions for prematurity over a three-year period. Obstetric case records were then reviewed to obtain the recorded time of onset of contractions when delivery was preceded by spontaneous labour. SETTING: A maternity hospital in the United Kingdom. MAIN OUTCOME MEASURES: The time of onset of spontaneous contractions which result in preterm labour and delivery. RESULTS: Four hundred and twenty-five women in preterm labour were studied. A significant diurnal rhythm in the timing of onset of contractions was noted with 42% of deliveries occurring in labour which commenced between midnight and 0600 hours. Subgroup analysis indicated that there was a significant rhythm in second trimester preterm labours, male and female babies and that this rhythm was present during both the winter and summer months. CONCLUSION: The periodicity of preterm labour onset demonstrates a rhythm which is similar to the rhythm in the onset of labour at term. Preterm labour most commonly begins between midnight and 0600 hours.

Circadian Rhythm↗

Teenage antenatal clinics may reduce the rate of preterm birth: a prospective study.

OBJECTIVE: To examine whether teenage antenatal clinics reduce the incidence of preterm birth. DESIGN: A multicentre prospective study was performed. SETTING: Three Australian hospitals with maternity services. POPULATION: Consecutive teenage patients (N= 731) were approached at their first or second antenatal visit. METHODS: Cases were women attending multidisciplinary teenage antenatal clinics and controls attended general hospital-based antenatal clinics. Teenage antenatal clinics involved multidisciplinary care and included guidelines to screen and treat all patients for infectious and social pathology. General antenatal clinic care was in accordance with Australian standards. MAIN OUTCOME MEASURES: Preterm birth, newborn biometry adjusted for gestational age, breastfeeding and contraception plans at discharge. RESULTS: Consent was obtained from 651 (89%) patients. Teenage pregnancy clinic patients were significantly less likely to present with threatened preterm labour (OR 0.45; 95% CI 0.29-0.68), preterm, prelabour, prolonged rupture of membranes (OR 0.34; 95% CI 0.18-0.63) or deliver preterm (OR 0.40; 95% CI 0.25-0.62) compared with those from general clinics. However, there was no independent effect of clinic care upon newborn biometry outcomes. Clinic care did not significantly alter rates of initiation of breastfeeding in hospital. However, significantly more of the teenage antenatal clinic mothers were discharged on contraception (OR 1.58; 95% CI 1.07-2.25). CONCLUSION: Teenage-specific antenatal clinics may reduce the rate of preterm birth.

Adolescent↗

TOCOX--a randomised, double-blind, placebo-controlled trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk.

OBJECTIVE: To assess the safety and efficacy of the long term prophylactic use of rofecoxib (a COX-2-specific inhibitor) in women at high risk of preterm delivery. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Queen Charlotte's and Chelsea Hospital, London and Guys and St Thomas' Hospitals, London. POPULATION: Ninety-eight singleton pregnancies at high risk of preterm labour. METHODS: Treatment from 16 to 32 weeks. Weekly ultrasound surveillance. MAIN OUTCOME MEASURES: Fetal renal function and ductus arteriosus blood flow changes. Preterm delivery rates and neonatal outcome. RESULTS: Rofecoxib caused a reduction in hourly fetal urine production rates (-34%, 95% CI -13 to -50%, P = 0.004) and amniotic fluid index (-2.2, 95% CI -3.2 to -1.2, P < 0.001). This effect did not increase with time on treatment and reversed in all cases on discontinuation of treatment. Rofecoxib had an effect on the ductus arteriosus, increasing maximum systolic velocity (0.1 m/s, 95% CI 0.03-0.16, P = 0.02) and minimum diastolic velocity (0.007 m/s, 95% CI 0.0007-0.013, P= 0.03). This effect increased with time on treatment but was reversed with discontinuation of treatment and had no long term clinical sequelae. There was no difference in preterm delivery rates <30 weeks (28% on placebo vs 33% on rofecoxib, Mantel-Haensel [M-H]-adjusted risk 1.11, 95% CI 0.67-1.87). There were more deliveries <37 weeks in those on rofecoxib (40%vs 67%, M-H-adjusted risk 1.59, 95% CI 1.09-2.32). Rates of preterm prelabour rupture of membranes (PPROM) were higher in those on rofecoxib (RR 2.5, 95% CI 1.3-4.7). CONCLUSION: Rofecoxib has a significant but reversible effect on fetal renal function and the ductus arteriosus. It does not reduce the incidence of early preterm delivery <30 weeks and is associated with an increased risk of delivery before 37 weeks in women at high risk.

Adult↗