Research on prevention of bilirubin-induced brain injury and kernicterus: National Institute of Child Health and Human Development conference executive summary. 2003

In July 2003, the National Institute of Child Health and Human Development convened a conference, "Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench-to-Bedside." This article will provide a summary of presentations and discussions from this conference. The summary will focus on the identified knowledge gaps in 5 areas related to bilirubin-induced brain injury and kernicterus: 1) neurobiology and neuroimaging; 2) epidemiology and issues of clinical management; 3) methodologies for assessing clinical jaundice and direct and noninvasive measurement of serum bilirubin and hemolysis; 4) therapies for management of neonatal hyperbilirubinemia; and 5) public health surveillance and systems-based approaches to prevention.     

Frequency of uterine contractions in asymptomatic pregnant women with or without a short cervix on transvaginal ultrasound scan

OBJECTIVE: The purpose of this study was to compare the frequency of uterine contractions in asymptomatic pregnant women with and without a short cervix (< 25 mm) on transvaginal ultrasound (TVU) and to determine the additive risk of contractions on the risk of preterm birth. STUDY DESIGN: The study involved secondary analysis of a blinded observational study of asymptomatic singleton pregnancies who were at high risk for preterm birth and who received both home uterine activity monitoring daily and transvaginal ultrasound of the cervix at 22 to 24 and 27 to 28 weeks of gestation. Thresholds for the maximum frequency of uterine contractions of 4 per hour and transvaginal ultrasound cervical length of 25 mm were used for analysis. Contraction frequency was compared in women with cervical length < 25 mm and > or =25 mm and was correlated with the risk of spontaneous preterm birth at < 35 weeks of gestation. RESULTS: Of the 303 women whose pregnancy was evaluated at 22 to 24 weeks of gestation, the 39 women (13%) with a cervical length of < 25 mm had 1.6 +/- 2.7 versus 1.2 +/- 2.0 contractions per hour in the 264 women (87%) with a cervical length of > or =25 mm (P=.37). At 27 to 28 weeks of gestation (n=295 women), contraction frequency was 3.2 +/- 3.7 versus 2.8 +/- 3.1 contractions per hour in women with a cervical length of < 25 mm (n=59 women; 20%) versus those with a cervical length of > or =25 mm (n=236 women; 80%; P=.34). Among women with a short cervix, the relative risks for spontaneous preterm birth were 2.0 (95% CI, 0.95-4.2) and 2.1 (95% CI, 1.06-4.3) for women with > or =4 contractions per hour compared with women with < 4 contractions per hour at 22 to 24 and 27 to 28 weeks of gestation, respectively. Results were confirmed by logistic regression analysis. CONCLUSION: The frequency of uterine contractions in asymptomatic women was not related significantly to cervical length of < 25 mm versus > or =25 mm. Among women with a cervical length of < 25 mm at 22 to 24 or 27 to 28 weeks of gestation, there was a trend toward a 2-fold increased risk of spontaneous preterm birth when the maximum contraction frequency was > or =4 per hour, compared to < 4 per hour.     

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.     

What we have learned about conducting randomized controlled trials in the NICHD MFMU network

The National Institute of Child Health and Human Development (NICHD) created the NICHD Maternal Fetal Medicine Units Network in 1986 to conduct randomized trials and observational studies in perinatal medicine to improve adverse pregnancy and infant outcomes. From 1986 to 2002, the Network has started 16 randomized trials. Five of the trials are described, with particular attention given to difficult issues that arose, such as feasibility, sample size estimation, randomization in very high risk pregnancies, changing clinical practice, importance of the study question to the investigators, and lack of recruitment. Changes that the Network group made to their organization and methodology as a result of these issues are described, together with their application to some of the other trials proposed and conducted by the group.     

What have we learned about uterine contractions and preterm birth? The HUAM Prediction Study

Measurement of uterine contraction frequency has been employed as a screening test to identify women with increased risk of preterm birth, and as an aid in the early diagnosis of preterm labor. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed a prospective, blinded observational study of uterine contraction frequency to detect and predict preterm labor and birth, respectively. The goal of the study was to assess the sensitivity, specificity, and positive and negative predictive value of various measures of uterine contraction frequency. Data collected from 306 women revealed that contraction frequency was significantly greater in women who would ultimately deliver before rather than after 35 weeks' gestation. However, both sensitivity and positive predictive value of any measure of contraction frequency to predict preterm birth were poor. Contraction frequency did not increase significantly within 1 or 2 weeks of an episode of preterm labor. These results serve to explain the absence of an association between contraction-based surveillance and preterm birth in randomized trials conducted in women at risk of preterm birth.     

Measuring quality of life in patients with breast cancer: a systematic review of reliable and valid instruments available in Japan

BACKGROUND: Little is known about the availability and psychometric properties of instruments to measure quality of life (QOL) in clinical research on Japanese patients with breast cancer. The purpose of this systematic review is to find reliable and valid instruments available in Japan, and to summarize their characteristics. METHODS: Instruments available in Japan were found through a systematic search of the literature. Each instrument identified was evaluated for item development, reliability, validity, interpretability and utility. RESULTS: Six questionnaires to measure health-related QOL (the QOL-ACD, the EORTC QLQ-C30, the EORTC QLQ-BR23, the FACT-B, the SF-36, the WHO/QOL-26) and five scales to quantify the psychological burden (the STAI, the POMS, the SDS, the HADS, the GHQ), for which reliability and validity have been documented, are available in Japanese. All instruments were developed in foreign countries except for the QOL-ACD. Two of the QOL questionnaires were specific to breast cancer (the EORTC QLQ-BR23, the FACT-B). Though the measurements can be interpreted in some manner, the meaning of change scores over time has been documented for only three instruments (the EORTC QLQ-C30, the FACT-B, and the GHQ). CONCLUSIONS: The review provides grounds for designing and implementing quantitative research on QOL of breast cancer patients in Japan. Methodological challenges, however, continue, particularly for validating instruments with regard to various study populations of Japanese people and demonstrating the clinical importance of change scores.     

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.