Francee Johnson

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

OBJECTIVE Our 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. STUDY DESIGN Anxiety, 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. RESULTS Analyses 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. CONCLUSION Stress 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.

Cervical competence as a continuum: A study of ultrasonographic cervical length and obstetric performance

OBJECTIVE Our purpose was to investigate the hypothesis that cervical competence is a continuum that is related to cervical length and is reflected by pregnancy history. STUDY DESIGN A cross-sectional study was performed of cervical length measured by transvaginal ultrasonography in women with prior preterm delivery at < or = 26 weeks, 27 to 32 weeks, and 33 to 35 weeks compared with women with cervical incompetence and normal controls delivered at term. RESULTS Transvaginal cervical length was measured during pregnancy in 32 subjects with cervical incompetence, 98 with previous preterm birth < or = 26 weeks, 98 with previous preterm birth at 27 to 32 weeks, 127 with previous preterm birth at 33 to 35 weeks, and 106 normal controls. The relationship between obstetric history and cervical length was evaluated by analysis of variance. The gestational age at the first preterm delivery was significantly correlated with cervical length in the current pregnancy at each gestational interval between 20 and 30 weeks in a continuous manner. CONCLUSION Cervical competence is a continuous rather than categoric variable and is indicated indirectly by measurement of the length of the cervix.

Obstetric determinants of neonatal survival: Influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants

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 obstetricians 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.

Follow-up of Children Exposed In Utero to 17 α-Hydroxyprogesterone Caproate Compared With Placebo

OBJECTIVE: To assess whether there are evident adverse effects of 17 &agr;-hydroxyprogesterone caproate after in utero exposure. METHODS: This study evaluated surviving children of mothers who participated in a multicenter placebo-controlled trial of weekly intramuscular 17 &agr;-hydroxyprogesterone caproate, with a 2:1 allocation to 17 &agr;-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child’s general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory. RESULTS: Of 348 eligible surviving children, 278 (80%) were available for evaluation (194 in the 17 &agr;-hydroxyprogesterone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 &agr;-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 &agr;-hydroxyprogesterone caproate and placebo groups. CONCLUSION: 17 &agr;-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters. LEVEL OF EVIDENCE: II

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.

The national institute of child health and human development maternal-fetal medicine unit network randomized clinical trial in progress : Standard therapy versus no therapy for mild gestational diabetes

It is recognized that women with gestational diabetes mellitus (GDM) who have significantly elevated fasting blood glucose levels are at increased risk for fetal macrosomia and perinatal morbidity if treatment is not provided (1,2). The association of milder forms of GDM with perinatal morbidity and mortality remains unclear, primarily because the condition is often confounded with other risk factors such as maternal obesity, age, and parity. Screening for GDM is recommended for most pregnant women, yet it is unknown whether there is a benefit to the identification and treatment of mild carbohydrate intolerance during pregnancy (3,4). The present report is an update of our previous description of a current ongoing randomized treatment trial for mild GDM (5). A randomized clinical trial of women with mild GDM (fasting glucose <95 mg/dl) is being undertaken that compares perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. This study aims to clarify whether there is utility in identifying and treating women with a normal fasting glucose level who meet standard criteria for GDM. We plan to compare perinatal outcomes in women who have been randomized to diet and/or insulin therapy with women who have been randomized to no specific treatment. A randomized treatment trial of mild GDM will clarify whether identification and treatment of mild GDM reduce perinatal morbidity. This information will assist in determining appropriate thresholds for the treatment of GDM. Overall, with broader identification and aggressive treatment, perinatal mortality rates associated with GDM appear to be similar to the nondiabetic population (1). Several analyses of 20 years ago did document an increased stillbirth rate for GDM pregnancies that would qualify as preexisting diabetes according to World Health Organization criteria (6–9). Below this threshold, the extent to …

Repeated courses of antenatal corticosteroids: are there effects on the infant's auditory brainstem responses?

Our objective was to assess the effects of repeated antenatal corticosteroid treatments on the neonatal auditory brainstem response (ABR), a sensitive measure of neonatal brain maturity and auditory function. To achieve this, we performed and blindly evaluated neonatal ABRs on a subset of infants delivering within a multicenter randomized placebo-controlled clinical trial comparing single versus repeated courses of antenatal corticosteroid treatments for women at 23-31 weeks gestation who remained at increased risk for preterm birth. The women were randomly assigned to either the single or the repeated antenatal corticosteroid treatment group. Women in the repeated antenatal corticosteroid group received weekly antenatal corticosteroid treatments until 34 weeks gestation or until they reached a study-determined limited number of courses, whereas women in the single antenatal corticosteroid group received an initial course of corticosteroid followed by weekly placebo injections. We performed ABR testing on their infants prior to discharge. The latencies of waves I, III and V and the peak-to-trough amplitudes of waves I and V were compared between those in the single (n=27) and repeated antenatal corticosteroid treatment (n=24) groups. The majority of repeated antenatal corticosteroid infants (20 of 24) were exposed to ≥ 4 antenatal corticosteroid treatments. Even though gestational age was similar between our subset of single and repeated antenatal corticosteroid treatment groups, infant birth weight and length and head circumference were significantly smaller in the repeated antenatal corticosteroid group (p <0.05). Despite these differences in birth sizes, there were no significant group differences in the ABR wave latencies or amplitudes. We concluded that our repeated antenatal corticosteroid treatments, in comparison to a single treatment, did not significantly benefit or harm the neonatal ABR despite significant effects on birth size.

Bone metabolism in fetuses of pregnant women exposed to single and multiple courses of corticosteroids

OBJECTIVE: To estimate the effect of single and recurrent doses of antenatal corticosteroids on fetal bone metabolism. METHODS: This was a secondary analysis of a cohort of pregnant women from a previously reported randomized, placebo-controlled, multicenter trial of women at risk for preterm delivery who received weekly courses of betamethasone (active) or placebo after an initial course of corticosteroids. Umbilical cord serum levels of carboxy-terminal carboxy-terminal propeptide of type I procollagen and cross-linked carboxy-terminal telopeptide of type I procollagen were measured to assess the rate of fetal bone formation and resorption, respectively. Analysis was stratified according to number of repeat antenatal study courses of betamethasone or placebo (one to three compared with at least four courses, not including the initial course). RESULTS: Of the 251 umbilical cord serum samples, the median serum carboxy-terminal telopeptide of type I procollagen levels, but not carboxy-terminal propeptide of type I procollagen levels, was significantly lower with repeat betamethasone exposure (55.0 compared with 57.9 micrograms/L, P=.01). In the fetuses exposed to at least four repeat study courses, there was a significant decrease in median carboxy-terminal telopeptide of type-I procollagen levels between repeat betamethasone exposure and placebo (53.4 compared with 58.6 micrograms/L, respectively, P=.04), but there was no difference between groups in the fetuses exposed to 1–3 repeat study courses (57.4 compared with 56.7 micrograms/L, respectively, P=.29). CONCLUSION: Levels of umbilical cord serum markers of bone resorption but not formation are reduced in fetuses exposed to repeat courses of antenatal betamethasone. Up to four courses of antenatal betamethasone do not seem to affect fetal bone metabolism. LEVEL OF EVIDENCE: II

Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals.

OBJECTIVE We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. STUDY DESIGN A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. RESULTS A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.

What we have learned about best practices for recruitment and retention in multicenter pregnancy studies

For 30 years, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network has had significant impact on clinical practice in obstetrics. The MFMU Network has conducted 50 randomized clinical trials and observational studies designed to improve pregnancy outcomes for mothers and children. Each center has a designated clinical research nurse coordinator who coordinates the day-to-day operations of each trial and leads a research team that is responsible for recruitment and retention of participants. Some of the lessons learned by the nurse coordinators over the past 30 years are described with examples from recent studies. Best practices that we have amassed from our experience are also described.