Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network.

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.

The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

Preterm prediction study: is socioeconomic status a risk factor for bacterial vaginosis in Black or in White women?

Bacterial vaginosis (BV), an important risk factor for preterm birth, is a more common infection in Black compared with White pregnant women. Because Black women in the United States are more likely to have lower measures of socioeconomic status (SES), this study examined the hypothesis that BV is associated with low SES. The project evaluated data from the Preterm Prediction Study of 2,929 women prospectively followed during their pregnancies. The women, who were screened for BV at 24 and 28 weeks of gestation, underwent a structured interview to evaluate demographic factors, SES, home and work environment, drug or alcohol use, and prior medical history. Black women in the study had many measures of lower SES compared with the White women, and reported less use of tobacco, alcohol and drugs. In neither the Black nor White women was an association found between BV and measures of SES (with the sole exception of "absence of a home telephone"). Most measures of SES do not explain the difference in rates of BV in Black and in White pregnant women.

The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.

OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.

Factors associated with term low birthweight in Cardiff, Wales.

This project was undertaken to examine the associations of a number of risk factors with impaired fetal growth, exemplified by delivery of a low-birthweight infant at term (TLBW). Utilising a large database of largely homogeneous (white) births in Wales, the Cardiff Births Survey, multivariable analysis by logistic regression examined the relative importance of these risk variables. Significant independent associations with TLBW were found (in decreasing order of magnitude) for low maternal weight, pre-eclampsia, smoking, short maternal height, late pregnancy bleeding, early pregnancy bleeding, history of a previous stillbirth, primiparity and older maternal age. In this population, risk of TBLW was associated with a number of demographic, medical and social factors. Of these, only smoking is likely to be modified by intervention.

Obstetric determinants of neonatal survival: influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN: In this prospective observational study we evaluated 713 singleton births of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age < 21 weeks were excluded. The obstetrician's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS: The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery.

The preterm prediction study: fetal fibronectin testing and spontaneous preterm birth. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. METHODS: Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22-24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spontaneous preterm birth at various intervals after the test was determined. RESULTS: In each testing period, 3-4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal fibronectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22-24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96-98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. CONCLUSION: A positive cervical or vaginal fetal fibronectin test at 22-24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.

Factors associated with preterm birth in Cardiff, Wales. I. Univariable and multivariable analysis.

OBJECTIVE: Our purpose was to examine the associations of demographic, social, and medical factors with risk of preterm birth. STUDY DESIGN: By use of the Cardiff Births Survey, a large database of largely homogeneous (white) births in Wales, multivariable analysis by logistic regression examined the relative importance of risk variables associated with preterm birth. RESULTS: Significant independent associations with preterm birth were found (in decreasing order of magnitude) for late pregnancy bleeding, preeclampsia-proteinuria, low maternal weight, low maternal age, early pregnancy bleeding, history of previous stillbirth, smoking, high parity, low or high hemoglobin concentration, history of previous abortion, low social class, bacteriuria, and nulliparity. CONCLUSION: In this population demographic, social, and medical characteristics of the pregnancies showed significant associations with preterm birth.

Factors associated with preterm birth in Cardiff, Wales. II. Indicated and spontaneous preterm birth.

OBJECTIVE: Our purpose was to examine and contrast associations of risk factors with spontaneous preterm birth and indicated preterm birth. STUDY DESIGN: Separate multiple logistic regression analyses were performed of indicated and spontaneous preterm births in a large database of births in Cardiff, Wales. RESULTS: Spontaneous preterm births were associated with young maternal age, low maternal weight, low or high parity, previous abortion, smoking, and early pregnancy bleeding. Indicated preterm births were associated with older age, low weight, previous stillbirth, bacteriuria, and early pregnancy bleeding. CONCLUSION: Spontaneous and indicated preterm births have different overall profiles of association with pregnancy risk factors.

[Cholestatic jaundice secondary to distention of the gallbladder caused by cystic duct syndrome]. / Ittero colestatico da ectasia della colecisti per sindrome del dotto cistico.

The Authors describe a rare case of cholestatic jaundice which persisted due to compression of the biliary tract by a hugely swollen gallbladder due to cystic duct syndrome.

A comparison of risk assessment models for term and preterm low birthweight.

BACKGROUND: Most epidemiological research dealing with the assessment of risk for low birthweight has focused on all low birthweight births. Studies that have attempted to distinguish between term and preterm low birthweights have tended to examine preterm low birthweight, since the risk of perinatal mortality and morbidity is greatest for this group of infants. METHOD: This study uses data from 25,408 singleton births in a 20-county region in North Carolina to identify and compare risk factors for term and preterm low birthweights, and also examines the usefulness of separate multivariate risk assessment systems for term and preterm low birthweights that could be used in the clinical setting. RESULTS: Risk factors that overlap as significant predictors of both types of low birthweight include race, no previous live births, smoking, weight under 100 lb, and previous preterm or low birthweight birth. Age also is a significant predictor of both types of low birthweight, but in opposite directions. Younger age is associated with reduced risk of term low birthweight and increased risk of pattern low birthweight. CONCLUSION: Comparison of all risk factors indicates that different multivariate models are needed to understand the epidemiology of preterm and term low birthweights. In terms of clinical value, a general risk assessment model that combines all low birthweight births is as effective as the separate models.

Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity.

We measured the concentration of progesterone and estradiol and calculated the progesterone:estradiol ratio in nonpregnant and pregnant human myometrium. Progesterone, estradiol and the progesterone:estradiol ratio were higher in pregnant than in nonpregnant myometrium. There was no difference in the concentration in the presence of labor. The progesterone:estradiol ratio showed a similar pattern. We also investigated the effect of the ovarian steroids on the activity of cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE). Progesterone in pharmacologic doses inhibited the activity of the high-affinity enzyme as much as 72% and the low-affinity form as much as 34%. High-affinity phosphodiesterase from nonpregnant myometrium was the least sensitive to inhibition, and the enzyme from pregnant myometrium obtained from laboring women was the most sensitive. Low-affinity phosphodiesterase from nonpregnant myometrium was less sensitive to inhibition than enzyme from pregnant women with or without labor. The degree of inhibition of the low-affinity enzyme in the two pregnant groups was not different. The type of inhibition was competitive in both the high- and low-affinity forms. Estradiol at similar concentrations did not have any effect on the activity of the enzyme. Progesterone in part may exert its effect on the human myometrium by its effect on cyclic adenosine monophosphate-PDE activity and the metabolism of cAMP.

Vaginal pH: a marker of preterm premature rupture of the membranes.

Preterm premature rupture of the membranes (PROM) is a common predecessor of preterm or low birth weight (LBW) birth, yet the risk of preterm PROM is presently unpredictable. Numerous infectious organisms that change the normal vaginal milieu have been associated with preterm PROM. Because these organisms alter vaginal pH, the use of pH was evaluated as a potential marker for women at increased risk for preterm PROM. Among 115 women at high risk for an LBW birth, those with a mean vaginal pH above 4.5 had a threefold increased risk of preterm PROM as compared with those with a mean pH of 4.5 or lower. Vaginal pH may be a useful marker to predict a woman's risk for preterm PROM.

Identification of women at high risk for preterm-low-birthweight births.

Preterm-low-birthweight births comprise a subset of extremely high-risk low-birthweight infants. While numerous studies have evaluated risk factors to predict an individual's chance of a high-risk pregnancy, few have identified risk factors specifically related to preterm-low-birthweight births. Risk factors for preterm-low-birthweight births were analyzed in a sample of 11,623 women from northwest North Carolina enrolled in a low-birth-weight prevention program. Significant risk factors for preterm-low-birthweight births in this population were identified, and weights were assigned to each factor. Application of the weighting system to each patient's specific risk factors identifies women at high risk for a preterm-low-birthweight birth and assists in the determination of appropriate intervention. These data make use of all current information in the low-birthweight births prevention project. Prospective assessment of the scoring system as the project continues should improve the ability to identify and intervene with women at highest risk for a preterm-low-birthweight birth.

Changes in cyclic adenosine monophosphate-phosphodiesterase activity in nonpregnant and pregnant human myometrium.

Cyclic adenosine monophosphate-phosphodiesterase is the enzyme responsible for cyclic adenosine monophosphate degradation. We investigated the kinetic behavior of this enzyme in the myometrium of women who were nonpregnant, pregnant at term not in labor, and pregnant at term in active labor. Phosphodiesterase activity was measured in the 100,000 g supernatant by the two-step isotopic procedure. The Km (Michaelis constant) value remains essentially unchanged from the nonpregnant to the pregnant state and subsequent labor in both the low and the high affinity enzymes. During pregnancy the V max (maximum velocity) is 75% less than in the nonpregnant state (p less than 0.005) and remains unchanged during labor. This is true for both the high and the low affinity enzymes. These changes in the kinetic characteristics of the cyclic adenosine monophosphate-phosphodiesterase are indicative of noncompetitive inhibition. We conclude that this inhibition may be interpreted as part of the mechanism for uterine smooth muscle relaxation and pregnancy maintenance.

Individualized cosinor assessment of circadian hormonal variation in third trimester human pregnancy.

Two clinically healthy pregnant women were studied in a single 24-h span during the third trimester. Blood drawn every 20 min was assayed for cortisol (F), dehydroepiandrosterone sulfate (DHEA-S), estriol (E3), and prolactin (PRL). Blood drawn hourly was assayed for progesterone (P), human placental lactogen (HPL) and 15alpha-hydroxyestriol (E4). Breast temperature (BT) was continuously monitored. Single cosinor analysis demonstrated statistically significant circadian rhythms for plasma concentrations of F, DHEA-S, and BT for both subjects, and of E3 for one subject. Statistically significant circadian rhythms in plasma concentrations of P, HPL, E4 or PRL could not be demonstrated in our third trimester subjects. However, analysis of data from subjects sampled at earlier gestational ages revealed highly significant PRL circadian rhythms. These results suggest that plasma concentrations of PRL show a progressive decrease in circadian amplitude despite a progressive increase in mesor with advancing gestational age. Frequent sampling and cosinor data analysis permit identification of circadian rhythms in BT. The use of BT as a potential marker for rhythms in plasma concentration of certain hormones awaits further scrutiny. The demonstration of several circadian endocrine rhythms in individual subjects in the third trimester of human pregnancy facilitates the usefulness of such marker rhythms.

Developmental aspects of pituitary and adrenal responses to arterial hypotension in neonatal, weanling, and adult sheep.

We have studied neuroendocrine and heart rate responses to arterial hypotension in unanesthetized, chronically cannulated neonatal (less than 10 days old), weanling (3- to 4-wk-old), and adult sheep. Nitroprusside-induced arterial hypotension in the absence of hypovolemia promptly increased plasma ACTH, vasopressin (AVP), and cortisol levels in all three groups. The integrated adenohypophyseal and neurohypophyseal responses to a standard hypotensive stimulus were similar at the three ages, suggesting that the functional development of the systems subserving these responses is complete by the immediate postnatal period. The integrated cortisol/ACTH ratio was greatest in the youngest animals, suggesting that enhanced adrenal responsiveness to ACTH exists in neonatal as well as in late-gestation fetal lambs. The reflex tachycardia accompanying the arterial hypotension in the weanling and adult sheep was absent in the neonates.

Subhourly variability of circulating third trimester maternal steroid concentrations as a source of sampling error.

Seven plasma samples from five normal third trimester pregnant women, drawn every 5 and 15 min at similar times on 2 days, 2 days apart, were measured in quadruplicate for estradiol (E2), estriol, progesterone, 16 alpha-hydroxyprogesterone, and 17 alpha-hydroxyprogesterone (17P). The mean of the 22 samples obtained from each subject for each steroid was used as a reference mean. Individual determinations were converted to percentages of the reference mean which was normalized to 0%. All pregnancies were uncomplicated, and all mean values were within the normal range for gestational age. Variability about the reference mean for single samples, however, range from a low of -80% to a high of 150%. The single sample, 95% confidence intervals for individual steroids pooled from the five subjects (110 determinations) range from +/- 36% (E2) to +/- 60% (17P). Mean percentage coefficients of variation between 5-min and 15-min sampling sequences were compared by analysis of variance. There is no significant difference between the mean percentage coefficients of variation of a 5-min as opposed to a 15-min sampling sequence for any of the hormones measured. The 95% confidence interval width around the reference mean is a function of the number of samples obtained. Because the 95% confidence interval width from 110 measurements decreases approximately as 1/ square root n with increasing sampling size, the decrement progressively diminishes. For E2, the least variable steroid, a one-sample 95% confidence interval width of +/- 36% decreases to approximately +/- 18% with four samples or approximately +/- 12% with nine samples. For 17P, the most variable steroid, a one-sample 95% confidence interval width of +/- 60% decreases to approximately +/- 30% with four samples or approximately +/- 20% with nine samples. Multiple sampling with plasma pooling is required for the accurate study of steroid concentrations in individual subjects in late pregnancy.