Rachel L. Copper

THE LENGTH OF THE CERVIX AND THE RISK OF SPONTANEOUS PREMATURE DELIVERY

BACKGROUNDnThe role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks gestation.nnnMETHODSnAt 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery.nnnRESULTSnWe examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile).nnnCONCLUSIONSnThe risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.

The preterm prediction study: Maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation ☆ ☆☆ ★

OBJECTIVEnOur purpose was to determine whether various measures of poor psychosocial status in pregnancy are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight.nnnSTUDY DESIGNnAnxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593 gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression analyses provided the odds ratios and 95% confidence intervals.nnnRESULTSnAnalyses revealed that stress was significantly associated with spontaneous preterm birth and with low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for psychosocial status, substance use, and demographic traits, black race was the only variable significantly associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low education were associated with spontaneous preterm birth and low birth weight.nnnCONCLUSIONnStress was associated with spontaneous preterm birth and low birth weight even after adjustment for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress, substance use, and other demographic factors.

Reduced Incidence of Preterm Delivery with Metronidazole and Erythromycin in Women with Bacterial Vaginosis

BACKGROUNDnPregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks gestation.nnnMETHODSnIn 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks gestation).nnnRESULTSnA total of 178 women (29 percent) delivered infants at less than 37 weeks gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04).nnnCONCLUSIONSnTreatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery.

A multicenter study of preterm birth weight and gestational age-specific neonatal mortality

OBJECTIVEnThis analysis was performed to present updated neonatal mortality data by age and birth weight for preterm newborns and to demonstrate the influence of plurality, ethnicity, and infant sex on mortality.nnnSTUDY DESIGNnPreterm birth weight and gestational age-specific mortality rates were compiled from the five centers that participated in the March of Dimes Multicenter Preterm Birth Prevention Project. In each center gestational age was assessed by standardized methods. A birth weight and gestational age-specific mortality chart for preterm births was created with live-birth data.nnnRESULTSnIn each birth weight group mortality decreased as the gestational age advanced; for each gestational age group heavier infants had less mortality. Female infants < 29 weeks survived better than male infants, and singletons < 29 weeks survived better than twins. Survival for black preterm newborns was better than that of whites but differences were not significant. Mortality for black term infants was significantly higher. The largest improvement in survival occurred between 25 and 26 weeks. At 30 weeks survival was > 90% and improved < 1% per week thereafter.nnnCONCLUSIONSnWhen compared with rates in previous reports, mortality rates appear to have improved, especially at gestational ages < 29 weeks. These data may be useful in decision-making and in counseling patients at risk for preterm delivery.

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 pretern 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.

Low-dose aspirin therapy to prevent preeclampsia

OBJECTIVEnOur aim was to test the hypothesis that acetylsalicylate (aspirin) treatment reduces the incidence or severity of pregnancy-associated hypertension.nnnSTUDY DESIGNnPatients were nulliparous, healthy, and with a singleton gestation at between 20 and 22 weeks gestation. A sample size of 600 patients was calculated on the basis of p < or = 0.05 and 90% power of observation. A 2-week placebo-controlled run-in was used to select compliant patients. Randomization occurred at 24 weeks, with 60 mg of aspirin or placebo treatment from randomization to delivery.nnnRESULTSnFollow-up was maintained on 99% of the patients. The randomized patients had a 94% pill compliance index. At randomization, serum thromboxane medians were similar in both groups. Thromboxane B2 levels in the aspirin group decreased significantly from baseline at 29 to 31 weeks, 34 to 36 weeks, and at delivery as compared with an overall increase in the placebo group. Preeclampsia developed in five of 302 women (1.7%) who received aspirin versus 17 of 302 (5.6%) who received the placebo (p = 0.009). Preeclampsia was severe in one aspirin and in six placebo recipients (p = 0.06).nnnCONCLUSIONnDaily ingestion of 60 mg of aspirin beginning at 24 weeks gestation significantly reduced the occurrence of preeclampsia.

Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery.

Objective To determine whether short cervical length or internal os funneling before 20 weeks gestation predicts early preterm birth or pregnancy loss in women with at least one prior spontaneous early preterm birth. Methods Transvaginal cervical ultrasound examinations were done every 2 weeks on 69 women with singleton gestations and histories of at least one prior spontaneous birth between 16 and 30 weeks gestation. The results of those examinations were correlated with gestational age at delivery. Results Among 53 women who had ultrasound examinations before 20 weeks gestation, those with cervical lengths at or below the tenth percentile for the study population (22 mm, n = 4) or funneling of the internal os (n = 5) were more likely than women without those factors to have spontaneous preterm births within 2 weeks (33% versus 0%, P = .01) or 4 weeks from the ultrasound examination (67% versus 0%, P < .001) or before 35 weeks gestation (100% versus 19%, P < .001). Short cervical length or funneling between 20–24 and 25–29 weeks was also associated with increased risk of spontaneous preterm birth before 35 weeks gestation (P ≤ .05 and P = .002, respectively) but not with increased risk of spontaneous preterm birth within 2 or 4 weeks of ultrasound examination. Conclusion Women with prior early spontaneous preterm births who have short cervical lengths or funneling of the internal cervical os before 20 weeks gestation are at increased risk of subsequent spontaneous preterm birth.

Plasma ferritin and pregnancy outcome

OBJECTIVEnPlasma ferritin is considered the best measure of total body iron, with low levels diagnostic of iron deficiency. High levels have been associated with inflammation and infection. We determined the relationship between plasma ferritin, birth weight, and preterm delivery.nnnSTUDY DESIGNnPlasma ferritin and hematocrit values were measured at 19, 26, and 36 weeks gestational age and correlated with birth weight and preterm delivery (< or = 32 and < 37 weeks) in 580 indigent black women.nnnRESULTSnHematocrit levels measured at any gestational age did not correlate significantly with birth weight or preterm delivery. Regardless of the gestational age of sampling, ferritin levels in the lowest quartile did not correlate significantly with subsequent preterm delivery. However, at 26 weeks, compared with the three lower quartiles, ferritin levels in the highest quartile were significantly associated with preterm delivery < or = 32 weeks, 6.5% versus 2.3% (p = 0.02), with preterm delivery < 37 weeks, 14% versus 8% (p = 0.04), and with birth weight < 1500 gm, 6.5% versus 2.0% (p = 0.01). Plasma ferritin levels in the highest quartile at 19, 26, and 36 weeks were associated with birth weight < or = 2500 gm, 14% versus 8% (p = 0.03), 12% versus 7% (p = 0.05), and 10% versus 2% (p = 0.0001), respectively, compared with the lower quartiles. Ferritin levels in the highest quartile were always associated with a lower mean birth weight than were those in the lower three quartiles: 19 weeks, 2999 gm versus 3225 gm, (p = 0.002); 26 weeks, 3065 gm versus 3257 gm, (p = 0.005); and 36 weeks, 3182 gm versus 3323 gm, (p = 0.009). Regression analyses controlling for multiple potential confounders confirmed that at 26 weeks ferritin levels in the highest quartile had an odds ratio and 95% confidence interval for preterm birth < 37 weeks of 2.0 (1.1 to 3.8), preterm delivery < or = 32 weeks of 2.7 (0.99 to 7.6), birth weight < or = 1500 gm of 3.9 (1.2 to 12.2), and birth weight < or = 2500 gm of 2.0 (1.0 to 4.0) compared with the three lower ferritin quartiles.nnnCONCLUSIONnHigh, but not low, plasma ferritin levels, especially at 26 weeks, were strongly associated with subsequent preterm delivery and birth weight.

What we have learned about the predictors of preterm birth

The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at < 32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and < l0th percentile cervical length (odds ratio, 5.8), and in serum, > 90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and > 75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at < 35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.

Neonatal periventricular-intraventricular hemorrhage after maternal β-sympathomimetic tocolysis

Abstract OBJECTIVE : Our objective was to determine if the rate of periventricular-intraventricular hemorrhage is increased in the offspring of women who received a β-sympathomimetic agent as part of the management of preterm labor. STUDY DESIGN : This retrospective study consists of 2827 women who were delivered of a singleton, live infant free of congenital neurologic anomalies between 25 and 36 completed weeks of gestation during a multicenter preterm birth prevention trial. The data were analyzed, adjusting for type of tocolytic agent, race, infant sex, gestational age, birth weight, health care center, route of delivery, indication for delivery, intrapartum fetal distress, respiratory distress syndrome, and neonatal sepsis. RESULTS : The overall incidence of periventricular-intraventricular hemorrhage in this population was 5.6%. in a univariate analysis in which no adjustment was made for potentially confounding variables, β-sympathomimetic tocolysis was found to be associated with nearly a fourfold increase in the incidence of periventricular-intraventricular hemorrhage when compared with the use of either magnesium sulfate or no tocolytic agent. The results of a multivariate regression analysis revealed that p-sympathomimetic agents were associated with a statistically significant increase in the overall incidence of periventricular-intraventricular hemorrhage (odds ratio 2.47, 95% confidence interval 1.34 to 4.56, p = 0.004) and a similar, but not significant, increase in the incidence of grades 3 and 4 periventricular-intraventricular hemorrhage (odds ratio 2.50, 95% confidence interval 0.96 to 6.48, p = 0.06). CONCLUSION : β-Sympathomimetic tocolytic therapy may be associated with a more than two fold increase in the incidence of neonatal periventricular-intraventricular hemorrhage. (Am J Obstet Gynecol 1992;167:873-9.)