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.

Risk factors for fetal death in white, black, and Hispanic women. Collaborative Group on Preterm Birth Prevention.

OBJECTIVE: To document the relation between stillbirth and various demographic, obstetric, and medical risk factors. METHODS: We analyzed the risk factors and medical origins of 403 stillbirths. The population studied included 34,350 births occurring during the March of Dimes Preterm Birth Prevention Trial. All births occurring in five perinatal centers from 1982-1986 were included in the analysis. Stillbirth was defined as those infants born at 20 weeks' gestation or later whose Apgar score was 0 at 1 and 5 minutes. RESULTS: Stillbirth occurred in 1.2% of all births. Fifty-one percent occurred before 28 weeks and only 18% were at term. Blacks had a greater risk of stillbirth when compared to other women. Prior preterm delivery yielded nearly a two-fold increase in the risk of stillbirth. Preeclampsia, chronic hypertension, and class A or class B-R diabetes were not associated with an increased risk of stillbirth. Other medical factors (hemoglobinopathies, Rh sensitization) resulted in a greater than sixfold increase in the rate of stillbirth, and congenital anomalies resulted in a fivefold increase. Abruption was associated with a 12-fold increase in the risk of stillbirth; nearly 14% of all stillbirths were associated with abruption. CONCLUSION: Eighty-two percent of all stillbirths occurred before term, and more than 50% occurred before 28 weeks. The majority of stillbirths were not explained by medical complications, but instead were often associated with other risk factors related to preterm birth. Further investigations are needed to understand the complex etiology of stillbirth.

Pregnancy outcome following a second-trimester loss.

OBJECTIVE: To evaluate the association between fetal loss in the second trimester and subsequent adverse birth outcomes. METHODS: We identified 95 women in our system who had a pregnancy loss at 13-24 weeks in the years 1985-1990 and tabulated the rates of preterm delivery, stillbirth, and neonatal death in the next pregnancy. We compared these outcomes to two groups: women who delivered at 25-36 weeks in their index pregnancy and those who delivered at term in their index pregnancy. RESULTS: Thirty-nine percent of women who had a pregnancy loss at 13-24 weeks in the index pregnancy had a preterm delivery in their next pregnancy, 5% had a stillbirth, and 6% had a neonatal death, with all outcomes worse than those found in the two control populations. Delivery at 19-22 weeks in the index pregnancy was associated with a 62% preterm delivery rate in the subsequent pregnancy. CONCLUSION: A second-trimester loss, especially one occurring at 19-22 weeks, is associated with a poor prognosis in the subsequent pregnancy.

The relationship of maternal attitude toward weight gain to weight gain during pregnancy and low birth weight.

OBJECTIVE: To evaluate the relationships between maternal attitude toward weight gain, actual weight gain, and infant birth weight. METHODS: Maternal attitude toward weight gain during pregnancy was assessed in 1000 women, using an 18-item questionnaire administered at a mean of 20 weeks' gestation. Composite scores were compared with pregnancy weight gain, maternal body mass index (BMI), and infant birth weight. RESULTS: In the total population, the attitude score was not significantly related to pregnancy weight gain (r = -0.05, P = .08) and was negatively associated with birth weight (r = -0.09, P < .004). Maternal body size as measured by BMI was strongly associated with both weight gain and birth weight. Obese women (BMI greater than 26.6) tended to have negative attitudes and had the lowest mean weight gain (10.2 kg), but had the heaviest babies (3400 g). Thin women (BMI less than 19.6) had significantly higher attitude scores and a higher mean weight gain (14.1 kg) than did obese women. A significantly larger proportion of thin women achieved recommended gains when compared with larger women, but had the lightest babies (3114 g). Within the group of thin women, after adjustment for smoking, race, and gestational age at delivery, attitude scores were not significantly associated with either weight gain or birth weight. CONCLUSION: Maternal attitude regarding weight gain is strongly influenced by pre-pregnancy body size; thin women tend to have positive attitudes and obese women tend to have negative attitudes about weight gain. Within BMI groups, a positive attitude does not predict appropriate weight gain or birth weight. These findings may explain in part why nutritional counseling programs tend to be associated with only minimal increases in birth weight.

Serum folate and fetal growth retardation: a matter of compliance?

Serum folate levels were measured at 30 weeks' gestational age in 289 pregnant women, each of whom had been provided with folate supplementation at enrollment in prenatal care. There was a significant association between low serum folate levels and fetal growth retardation. High folate levels were most likely explained by recent folic acid intake. Therefore, we were concerned that the decreased fetal growth associated with low folate levels may have been related to a combination of psychological and behavioral characteristics for which low serum folate levels were only a surrogate measure. A profile of maternal psychosocial status was created, which included measures of depression, anxiety, self-esteem, mastery, stress, and social support. Poorer psychological scores were significantly related to lower serum folate levels. However, in women with both good and poor psychosocial scores, high folate levels were significantly associated with increased birth weight, a relationship that persisted even after adjusting for maternal race, body mass index, smoking, history of a low birth weight infant, and infant gender. Our findings suggest that women with good psychosocial scores are more likely to take folate, but that the use of folate itself is related to a lower risk of fetal growth retardation and increased birth weight.

The relationships among psychosocial profile, maternal size, and smoking in predicting fetal growth retardation.

OBJECTIVE: We explored the relationships among measures of psychosocial well-being, maternal size, and smoking in predicting infant size at birth. METHODS: Participants in this population-based cohort study were drawn from public health prenatal clinics in Jefferson County, Alabama during 1985-1988. Para 1 and 2 women were screened for 11 risk factors for low birth weight, including small stature, a previous low birth weight infant, and smoking. RESULTS: Poor scores on five of six psychosocial scales, as well as on a combined profile, were associated with a significantly higher relative risk of fetal growth retardation (FGR) only in thinner women, defined as having a body mass index less than the median (relative risk [RR] 2.11, 95% confidence interval [CI] 1.47, 3.04). A significant association between the psychosocial profile and birth weight was demonstrated for thin women in a multivariate analysis adjusting for gestational age, race, infant sex, and smoking (P = .0003). The relationship remained significant when hypertension, alcohol and drug use, and weight gain were added to the model (P = .003). In women with a body mass index above the median, a poor psychosocial profile showed little association with FGR (RR 1.20, 95% CI 0.73, 1.98) and did not have a significant association with birth weight. A poor profile had a greater association with FGR in non-smokers (RR 2.04, 95% CI 1.29, 3.22) than in smokers (RR 1.4, 95% CI 0.95, 2.06). CONCLUSIONS: Greater pre-pregnancy weight for height appears to protect against the adverse effects of a poor psychosocial profile in a population of poor, primarily black women. In thinner women, both smoking and a poor psychosocial profile were associated with a substantially increased rate of FGR, indicating a subgroup of women who may receive greater benefits from intervention programs.

The influence of previous low birth weight on birth weight, gestational age, and anthropometric measurements in the current pregnancy.

The effect of a previous low birth weight birth (less than 2750 g) was examined using a series of regression analyses. Effects on birth weight were partitioned into those associated with preterm delivery (128 g) and term delivery (178 g). Among term births, a mean difference of 107 g was associated with a previous birth of less than 2750 g, even after controlling for other risk factors including smoking, drug and alcohol use, maternal race, size, and hypertension. The pattern of measurements seen after a previous birth of less than 2750 g included significantly smaller head, chest, abdomen, arm, and thigh circumferences, but an insignificant impact on skinfold thicknesses and no significant effect on length measurements.

The Alabama preterm birth prevention project.

A preterm birth prevention program consisting of risk scoring, intensive weekly observation including cervical examinations, and detailed education about preterm labor signs and symptoms was tested in a predominantly black, indigent population. One thousand high-risk women were randomized to treatment or control groups. Although more preterm labor was diagnosed and treated in the treatment group, there were no significant differences between the groups with respect to mean birth weight or gestational age, spontaneous preterm delivery rates, or low or very low birth weight rates. The rates of respiratory distress syndrome and fetal and neonatal mortality, although greater in the treatment group, were not statistically different. However, the treatment-group infants had significantly more intracranial hemorrhages and spent more days on ventilators. At this institution, the preterm birth prevention program was not effective.

Etiologies of preterm birth in an indigent population: is prevention a logical expectation?

To assess the expectations of preterm birth prevention, we determined the causes of preterm birth in a population of indigent women. We studied 13,119 singleton births in a predominantly black, indigent population occurring between November 1982 and April 1986 to identify the proportion of preterm births that may have been prevented using current treatment modalities. Forty-four percent of the preterm births occurred at 35 to 36 weeks' gestational age, a time when most practitioners do not attempt tocolysis. Of the remainder, 17% occurred before 35 weeks but were indicated for maternal medical or obstetric complications, and another 17% occurred before 35 weeks but followed spontaneous premature rupture of the membranes. Therefore, of the 1445 preterm births, we calculated that only 336 (23.2%) were theoretically preventable. A fourth of these presented at less than 3 cm cervical dilatation and were treated appropriately with tocolytics, but delivered anyway. Therefore, most of the potentially preventable births occurred in the group that presented with cervical dilatation of more than 3 cm. We conclude that improving the preterm birth rate significantly below current levels may be difficult to achieve.

The predictive value of umbilical artery Doppler studies for preeclampsia or fetal growth retardation in a preeclampsia prevention trial.

OBJECTIVE: To determine the clinical utility of longitudinal Doppler umbilical artery systolic-diastolic ratios (S/D) to predict the occurrence of either preeclampsia or fetal growth retardation (FGR) in a low-risk population. METHODS: Healthy nulliparas with singleton gestations were enrolled in a double-blind trial of low-dose (60 mg) aspirin for preeclampsia prevention. Treatment was initiated at 24 weeks and continued until delivery. Continuous-wave Doppler studies were scheduled before assignment to treatment and at 27-31, 32-36, and 37-42 weeks. Preeclampsia was defined as a persistent diastolic blood pressure of at least 90 mmHg with proteinuria, and FGR was defined as birth weight below the tenth percentile. Doppler values were considered abnormal if they exceeded the 90th percentile for the gestational age range in the study population. Summary predictive values were computed for the abnormal S/D at each gestational age interval. To assess the potential effect of the administration of low-dose aspirin, logistic regression was used to model the relation between the Doppler indices, aspirin use, and these abnormal pregnancy outcomes. RESULTS: A total of 1665 Doppler examinations were performed on 565 women. Forty-four fetuses developed FGR and 21 women were diagnosed with preeclampsia. The positive predictive values of an abnormal S/D for the subsequent development of FGR were 13-17% across the gestational age ranges studied, and the positive predictive values for preeclampsia were 0-5%. Aspirin treatment did not affect the relation between the Doppler indices and these outcomes in the logistic regression model. CONCLUSION: Elevated umbilical artery S/D is not a clinically useful predictor of either FGR or preeclampsia in a low-risk population.

Anthropometric assessment of body size differences of full-term male and female infants.

OBJECTIVE: To determine gender-specific differences in anthropometric characteristics of full-term male and female infants. METHODS: Twelve hundred five term newborn infants were examined. All measures of length and skinfold thickness were performed in a standardized manner. RESULTS: After adjusting for confounding variables by regression analysis, we found that nearly all length and circumference measurements were significantly smaller in female infants than in male infants but that subcutaneous fat deposition in female infants was significantly increased. However, there was no difference in the ponderal index between male and female newborns, indicating that this measure does not correlate with newborn fat deposition across the sexes. CONCLUSIONS: Despite being shorter and having smaller circumferences, female infants have more subcutaneous fat than male infants. The ponderal index is not useful as a measure of fatness when the sexes are compared. We speculate that the greater subcutaneous fat deposition in female infants may be related to their better neonatal outcomes.

The origin and outcome of preterm twin pregnancies.

OBJECTIVE: To define the etiology of preterm twin births and determine the contribution of twin births to preterm birth and related morbidity and mortality. METHODS: The March of Dimes Multicenter Prematurity and Prevention Study included a total of 33,873 women who delivered between 1982-1986, 432 (1.3%) of which delivered twins. Women were classified by reason for preterm birth and ethnicity. Neonates were classified as to stillbirth, neonatal death, and various short-term morbidities. A second data set from one center consisted of infants who weighed 1000 g or less, were born between 1979-1991, and survived to 1 year of age (n = 386, 15% twins); this was used to determine if twins and singletons born at comparable gestational ages have a similar risk for major developmental handicaps. RESULTS: Of the deliveries in the data set, 54% of twins were preterm compared with 9.6% among singletons. Of those born preterm, twins were born at a significantly earlier gestational age than were singletons. Only 2.6% of all neonates born were twins, but they represented 12.2% of all preterm infants, 15.4% of all neonatal deaths, and 9.5% of all fetal deaths. Spontaneous labor accounted for 54% of twin births, premature rupture of membranes accounted for 22%, and indicated deliveries accounted for 23%. Of the indicated preterm births in twins, 44% were due to maternal hypertension, 33% to fetal distress or fetal growth restriction, 9% to placental abruption, and 7% to fetal death. Comparing infants of similar gestational age, twins weighed less, but had a mortality equivalent to that of singletons after 29 weeks. Between 26-28 weeks' gestation, the risk of mortality for twins versus singletons was 1.6 (95% confidence interval 1.1-2.5). Preterm twins did not have significantly more respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, or other short-term morbidity than did preterm singletons. Twins who weighed 500-1000 g and survived to 1 year had a 25% rate of major developmental handicaps. However, when gestational age was controlled, the rate of major handicaps was not higher in twins than in singletons. CONCLUSIONS: Twins accounted for a disproportional amount of preterm birth and associated morbidity and mortality. Also, when preterm twins were compared with preterm singletons and corrected for their gestational ages, the rates of morbidity were similar. Preterm twins weighing less than 1000 g did not have an increased prevalence of major handicaps at 1 year of age compared with preterm singletons.

Amniotic fluid lipid profiles: a rapid gas chromatographic method.

The lipid extract of amniotic fluid has been analysed for the important fatty acids derived mainly from the lecithin component of lung surfactant. Using gas-liquid chromatography and mass spectrometry, these fatty acids have been identified. A positive correlation between certain lipid profiles and lack of lung surfactant with its associated respiratory problems for the newborn infant has been demonstrated.

Plasma and erythrocyte zinc concentrations and their relationship to dietary zinc intake and zinc supplementation during pregnancy in low-income African-American women.

OBJECTIVE: To evaluate the effects of usual dietary intake of zinc and of zinc supplementation during pregnancy on plasma and erythrocyte zinc concentrations. DESIGN: A randomized, double-blind, placebo-controlled trial. SUBJECTS: Low-income African-American women (n = 580) assigned randomly to groups at 19 weeks of gestation. INTERVENTION: A daily dose of zinc (25 mg) or a placebo until delivery. MAIN OUTCOME MEASURES: Plasma, erythrocyte, and dietary zinc levels. STATISTICAL ANALYSES: Multiple regression and repeated measures analysis of variance. RESULTS: In both the placebo and the supplemented groups, when all subjects were grouped by usual dietary zinc intake above or below the median (12 mg/day), results were the same: Women with high dietary zinc intake had higher erythrocyte zinc levels at the time of randomization and at all subsequent measurements during pregnancy than those who had low dietary zinc intake (P < or = .06; difference not significant for zinc-supplemented group); no difference was observed for plasma zinc levels. On the other hand, when the subjects were stratified at the median by total daily zinc intake (usual dietary zinc + 25 mg zinc supplement) during pregnancy, a significant difference in plasma zinc levels (P < .005) was found between women with high total zinc intake (mean = 38 mg/day) and low total intake (mean = 13 mg/day) at 26, 32, and 38 weeks of gestation; however, no such differences were found in erythrocyte zinc levels. APPLICATIONS: These results should help dietitians and other health professionals better understand the expected changes in plasma and erythrocyte zinc levels during pregnancy, and the relationship between dietary and supplemental zinc and zinc nutriture.

Determinants of zinc intake in low-income black and white pregnant women.

A prospective study was conducted to evaluate and compare the determinants of dietary zinc intake in black and white low-income pregnant women. The study population consisted of 1298 low-income women (70% Black, 30% White) who received prenatal care at University Hospital at the University of Alabama in Birmingham from 1985 to 1989. Various maternal characteristics were evaluated at the first prenatal visit. Two 24 h recalls were obtained at 18 and 30 wk of gestation to calculate the intakes of dietary zinc and other nutrients. Student's t test, chi2, Pearson correlation coefficients, and multiple regression analyses were used to compare and evaluate the determinants of zinc and other nutrient intakes in Black and White subjects. The mean prepregnancy body mass index and the mean intake of zinc, energy, and all the other nutrients except calcium were significantly higher in Black than in White subjects. There was a significant correlation between zinc and energy intake (r = 0.69, p = 0.001). Age, marital status, parity, socioeconomic status, smoking, and alcohol intake were not significant predictors of zinc or other nutrient intakes. After adjusting for energy intake, race was the only significant predictor of dietary zinc intake. Race and energy intake explained 24% of the variation in zinc intake. Results of this study indicate that after adjusting for other covariates, race and energy intakes are the only predictors of zinc intake in low-income pregnant women.

Factors influencing plasma zinc levels in low-income pregnant women.

Plasma zinc (Zn) concentrations were measured in 4376 indigent women (86% African-American), at at mean (+/- SD) gestational age of 15 (+/- 7.8) wk to determine the relationship between various maternal characteristics and plasma Zn levels during pregnancy. Mean Plasma An levels were lower in African-American women than in Caucasian women, in multiparous women than in primiparous women, and in women with body weight > 69.9 kg than in those with body weight < or = 69.9 kg (p < or = 0.001 for each comparison). There were no significant differences related to maternal age, marital status, education, or smoking habit. Multiple regression analysis, including maternal prepregnancy weight, race, age, parity, smoking habit, education, and marital status indicated that race, parity, and pregnancy weight were significantly associated with maternal plasma Zn levels, adjusted for gestational age. Maternal race was the best predictor of plasma Zn concentrations among the population of pregnant women studied A significant proportion of variance in maternal plasma Zn levels. remained unexplained after taking into account various maternal characteristics. The reasons for lower plasma Zn levels in African-American women, compared to Caucasian women, during pregnancy are unknown.

Catecholamine secretion in fetal adaptation to stress.

From the beginning of labor, the fetus must successfully adapt from intrauterine life to the stress of birth and, finally, to extrauterine life. The role of hormones known as catecholamines in this adaptive mechanism is described. An understanding of the physiology of catecholamine secretion will enhance the nursing care of mothers and their infants during this important transitional period.

Evaluation of a risk scoring system as a predictor of preterm birth in an indigent population.

A risk scoring system designed to predict spontaneous preterm birth was implemented in a large, indigent population as part of a multicenter trial of preterm birth prevention. A total of 7478 women with singleton gestations were screened and followed up prospectively at the Birmingham project center. Patients who had an indicated preterm delivery or a fetal anomaly were excluded from the study population. Analysis by assigned risk score and parity showed that, whereas the sensitivity and positive predictive value were better in multiparous women than in nulliparous women, overall the values were low. Logistic regression analyses of the multiparous and nulliparous populations showed independent sets of significant (p less than or equal to 0.05) risk variables. A history of preterm delivery and a low prepregnancy weight were the most predictive risk factors in the multiparous and nulliparous models, respectively. We conclude that the clinical usefulness of a risk scoring system to predict spontaneous preterm birth in an indigent population is limited.

Are pill counts valid measures of compliance in clinical obstetric trials?

We compared pill counts with a biochemical measure of compliance in 283 women who participated in a randomized double-blind trial that evaluated the efficacy of low-dose aspirin in the prevention of preeclampsia. Subjects whose pill counts indicated a usage > 100% were less compliant than women with lower pill counts.

The relationship between maternal skinfold thickness, smoking and birthweight in black and white women.

A prospective study was conducted in a sample of 1491 multiparous women to ascertain whether the relationship between maternal tricep skinfold thickness and infant birthweight is modified by smoking status and whether the relationship is different in white and black infants. Maternal tricep skinfold thickness measured at midpregnancy was a significant predictor of infant birthweight in both white and black infants after adjusting for gestational age at birth, maternal height, maternal age, parity, alcohol consumption and sex of the infant. However, maternal tricep skinfold thickness was a better predictor of birthweight in smokers compared with nonsmokers. Both white and black women with tricep skinfold thickness below the sample mean had lower infant birthweight than women with tricep skinfold at or above the mean, after adjusting for gestational age at birth, but the difference was greater in smokers (198 g for white and 221 g for black infants) than in nonsmokers (124 g for white and 221 g for black infants) than in nonsmokers maternal subcutaneous fat measured by tricep skinfold thickness has a greater effect on infant birthweight in smokers compared with nonsmokers, with similar effects in white and black infants.