Genetic Patterns of Selected Muscular Dystrophies in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

Background and Objectives: To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States. Methods: This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Variants of unknown significance (VUSs) from the original genetic test reports were reanalyzed for changes in interpretation. Results: Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes (EMD) and autosomal genes reported to have skewed gender ratios (ANO5, CAV3, and LMNA). The most common associated genes were FKRP, CAPN3, ANO5, and DYSF. Reanalysis yielded more definitive variant interpretations for 60 of 144 VUSs, with a mean interval between the original clinical genetic test of 8.11 years for all 144 VUSs and 8.62 years for the 60 reclassified variants. Ten individuals were found to have monoallelic pathogenic variants in genes known to be primarily recessive. Discussion: This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

DMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians.

ABSTRACT: The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype-phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.

Sources of variation in estimates of Duchenne and Becker muscular dystrophy prevalence in the United States.

BACKGROUND: Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence. RESULTS: The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source's contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age-site-race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained. CONCLUSION: Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution.

Role Attainment in Emerging Adulthood: Subjective Evaluation by Male Adolescents and Adults with Duchenne and Becker Muscular Dystrophy.

BACKGROUND: Youth with Duchenne and Becker muscular dystrophy (DBMD) experience challenges in attaining adult roles, which may impact quality of life. New interventions and treatments may facilitate adult role attainment through improved function. Historical data on adult role attainment is important to assess the impact of new interventions on teens and young adults with DBMD. This study assesses medical knowledge, independence and employment, and relationships among adolescents and young adults with DBMD. METHODS: This study uses data from a 2013 Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) survey on adult transition. Males with DBMD aged 16-30 years were included. RESULTS: Sixty-five of 258 eligible males participated; we report results on 60 participants with an MD STARnet case definition of DMD or BMD. Individuals with BMD reported higher rates than those with DMD of frequently staying home without supervision (50% BMD; 14% DMD), independently performing daily physical needs (93% BMD; 7% DMD) and being employed full or part time (33% BMD; 4% DMD). Most participants understood medication and physical therapy goals; less than half indicated being often or always responsible for scheduling DMBD-related management and refilling medications. Most had not been in a romantic relationship but reported desiring such relationships. CONCLUSIONS: Our data reinforce the impact of DMD (and to a lesser extent, BMD) on transition to adult roles. These results provide an important historical comparator for teen and adult patients who are trying new interventions and therapies. Such data are important for assessing the quality-of-life impact of new treatments and to inform support and training programs for people with DBMD as they transition to new adult roles and responsibilities.

Health Profile of Preterm Males With Duchenne Muscular Dystrophy.

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.

Association of genetic mutations and loss of ambulation in childhood-onset dystrophinopathy.

BACKGROUND: Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood-onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design. METHODS: Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982 to 2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon-skipping therapy (exons 8, 20, 44-46, 51-53) and another group. Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR = 0.22; 95% CI = 0.08, 0.63) and 44 (HR = 0.30; 95% CI = 0.12, 0.78) were associated with delayed LoA compared to other exon deletions. CONCLUSIONS: Delayed LoA in males with mutations amenable to exon-skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization.

Recurrent thrombosis in patients with antiphospholipid antibodies and an initial venous or arterial thromboembolic event: A systematic review and meta-analysis.

BACKGROUND: Patients with antiphospholipid antibodies (aPL) and thromboembolism (TE) are at risk for recurrent TE. Few studies, however, distinguish patients based on the initial event. OBJECTIVES: We performed a systematic review and meta-analysis to investigate patients with aPL and venous TE (VTE), provoked or unprovoked, and patients with arterial TE (ATE). PATIENTS/METHODS: We conducted searches in PubMed, CINAHL, Cochrane, and EMBASE. Inclusion criteria were prospective trials or cohort studies investigating patients with aPL and ATE or VTE. Excluded studies did not provide estimated recurrence rates, did not specify whether the incident event was ATE or VTE, included patients with multiple events, or included <10 patients. Two-year summary proportions were estimated using a random effects model. RESULTS: Ten studies described patients with VTE, 2 with ATE, and 5 with VTE or ATE. The 2-year proportion for recurrent TE in patients with VTE who were taking anticoagulant therapy was 0.054 (95% confidence interval [CI], 0.037-0.079); the 2-year proportion for patients not taking anticoagulant therapy was 0.178 (95% CI, 0.150-0.209). Most studies did not distinguish whether VTE were provoked or unprovoked. The 2-year proportion for recurrent TE in patients with ATE who were taking anticoagulant therapy was 0.220 (95% CI, 0.149-0.311); the 2-year proportion for patients taking antiplatelet therapy was 0.216 (95% CI, 0.177-0.261). CONCLUSIONS: Patients with aPL and ATE may benefit from a different antithrombotic approach than patients with aPL and VTE. Prospective studies with well-defined cohorts with aPL and TE are necessary to determine optimal antithrombotic strategies.

The Effect of Laboratory Test-Based Clinical Decision Support Tools on Medication Errors and Adverse Drug Events: A Laboratory Medicine Best Practices Systematic Review.

BACKGROUND: Laboratory and medication data in electronic health records create opportunities for clinical decision support (CDS) tools to improve medication dosing, laboratory monitoring, and detection of side effects. This systematic review evaluates the effectiveness of such tools in preventing medication-related harm. METHODS: We followed the Laboratory Medicine Best Practice (LMBP) initiative's A-6 methodology. Searches of 6 bibliographic databases retrieved 8508 abstracts. Fifteen articles examined the effect of CDS tools on (a) appropriate dose or medication (n = 5), (b) laboratory monitoring (n = 4), (c) compliance with guidelines (n = 2), and (d) adverse drug events (n = 5). We conducted meta-analyses by using random-effects modeling. RESULTS: We found moderate and consistent evidence that CDS tools applied at medication ordering or dispensing can increase prescriptions of appropriate medications or dosages [6 results, pooled risk ratio (RR), 1.48; 95% CI, 1.27-1.74]. CDS tools also improve receipt of recommended laboratory monitoring and appropriate treatment in response to abnormal test results (6 results, pooled RR, 1.40; 95% CI, 1.05-1.87). The evidence that CDS tools reduced adverse drug events was inconsistent (5 results, pooled RR, 0.69; 95% CI, 0.46-1.03). CONCLUSIONS: The findings support the practice of healthcare systems with the technological capability incorporating test-based CDS tools into their computerized physician ordering systems to (a) identify and flag prescription orders of inappropriate dose or medications at the time of ordering or dispensing and (b) alert providers to missing laboratory tests for medication monitoring or results that warrant a change in treatment. More research is needed to determine the ability of these tools to prevent adverse drug events.

Interventions to prevent iatrogenic anemia: a Laboratory Medicine Best Practices systematic review.

BACKGROUND: As many as 90% of patients develop anemia by their third day in an intensive care unit (ICU). We evaluated the efficacy of interventions to reduce phlebotomy-related blood loss on the volume of blood lost, hemoglobin levels, transfusions, and incidence of anemia. METHODS: We conducted a systematic review and meta-analysis using the Laboratory Medicine Best Practices (LMBP) systematic review methods for rating study quality and assessing the body of evidence. Searches of PubMed, Embase, Cochrane, Web of Science, PsychINFO, and CINAHL identified 2564 published references. We included studies of the impact of interventions to reduce phlebotomy-related blood loss on blood loss, hemoglobin levels, transfusions, or anemia among hospital inpatients. We excluded studies not published in English and studies that did not have a comparison group, did not report an outcome of interest, or were rated as poor quality. Twenty-one studies met these criteria. We conducted a meta-analysis if > 2 homogenous studies reported sufficient information for analysis. RESULTS: We found moderate, consistent evidence that devices that return blood from flushing venous or arterial lines to the patient reduced blood loss by approximately 25% in both neonatal ICU (NICU) and adult ICU patients [pooled estimate in adults, 24.7 (95% CI = 12.1-37.3)]. Bundled interventions that included blood conservation devices appeared to reduce blood loss by at least 25% (suggestive evidence). The evidence was insufficient to determine if these devices reduced hemoglobin decline or risk of anemia. The evidence suggested that small volume tubes reduced the risk of anemia, but was insufficient to determine if they affected the volume of blood loss or the rate of hemoglobin decline. CONCLUSIONS: Moderate, consistent evidence indicated that devices that return blood from testing or flushing lines to the patient reduce the volume of blood loss by approximately 25% among ICU patients. The results of this systematic review support the use of blood conservation systems with arterial or venous catheters to eliminate blood waste when drawing blood for testing. The evidence was insufficient to conclude the devices impacted hemoglobin levels or transfusion rates. The use of small volume tubes may reduce the risk of anemia.

From Clinical Phenotype to Genotypic Modelling: Incidence and Prevalence of Recessive Dystrophic Epidermolysis Bullosa (RDEB).

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited genetic disorder characterized by recurrent and chronic open wounds with significant morbidity, impaired quality of life, and early mortality. RDEB patients demonstrate reduction or structural alteration type VII collagen (C7) owing to mutations in the gene COL7A1, the main component of anchoring fibrils (AF) necessary to maintain epidermal-dermal cohesion. While over 700 alterations in COL7A1 have been reported to cause dystrophic epidermolysis bullosa (DEB), which may be inherited in an autosomal dominant (DDEB) or autosomal recessive pattern (RDEB), the incidence and prevalence of RDEB is not well defined. To date, the widely estimated incidence (0.2-6.65 per million births) and prevalence (3.5-20.4 per million people) of RDEB has been primarily characterized by limited analyses of clinical databases or registries. METHODS: Using a genetic modelling approach, we use whole exome and genome sequencing data to estimate the allele frequency of pathogenic variants. Through the ClinVar and NCBI database of human genome variants and phenotypes, DEB Register, and analyzing premature COL7A1 termination variants we built a model to predict the pathogenicity of previously unclassified variants. We applied the model to publicly available sequences from the Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) and identified variants which were classified as pathogenic for RDEB from which we estimate disease incidence and prevalence. RESULTS: Genetic modelling applied to the whole exome and genome sequencing data resulted in the identification of predicted RDEB pathogenic alleles, from which our estimate of the incidence of RDEB is 95 per million live births, 30 times the 3.05 per million live birth incidence estimated by the National Epidermolysis Bullosa Registry (NEBR). Using a simulation approach, we estimate a mean of approximately 3,850 patients in the US who may benefit from COL7A1-mediated treatments in the US. CONCLUSION: We conclude that genetic allele frequency estimation may enhance the underdiagnosis of rare genetic diseases generally, and RDEB specifically, which may improve incidence and prevalence estimates of patients who may benefit from treatment.

The effect of steroid treatment on weight in nonambulatory males with Duchenne muscular dystrophy.

To describe the long-term effect of steroid treatment on weight in nonambulatory males with Duchenne Muscular Dystrophy (DMD), we identified 392 males age 7-29 years with 4,512 weights collected after ambulation loss (176 steroid-naïve and 216 treated with steroids ≥6 months) from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Comparisons were made between the weight growth curves for steroid-naïve males with DMD, steroid-treated males with DMD, and the US pediatric male population. Using linear mixed-effects models adjusted for race/ethnicity and birth year, we evaluated the association between weight-for-age and steroid treatment characteristics (age at initiation, dosing interval, cumulative duration, cumulative dose, type). The weight growth curves for steroid-naïve and steroid-treated nonambulatory males with DMD were wider than the US pediatric male growth curves. Mean weight-for-age z scores were lower in both steroid-naïve (mean = -1.3) and steroid-treated (mean = -0.02) nonambulatory males with DMD, compared to the US pediatric male population. Longer treatment duration and greater cumulative dose were significantly associated with lower mean weight-for-age z scores. Providers should consider the effect of steroid treatment on weight when making postambulation treatment decisions for males with DMD.

Interventions to Improve Follow-Up of Laboratory Test Results Pending at Discharge: A Systematic Review.

Failure to follow up test results pending at discharge (TPAD) from hospitals or emergency departments is a major patient safety concern. The purpose of this review is to systematically evaluate the effectiveness of interventions to improve follow-up of laboratory TPAD. We conducted literature searches in PubMed, CINAHL, Cochrane, and EMBASE using search terms for relevant health care settings, transition of patient care, laboratory tests, communication, and pending or missed tests. We solicited unpublished studies from the clinical laboratory community and excluded articles that did not address transitions between settings, did not include an intervention, or were not related to laboratory TPAD. We also excluded letters, editorials, commentaries, abstracts, case reports, and case series. Of the 9,592 abstracts retrieved, eight met the inclusion criteria and reported the successful communication of TPAD. A team member abstracted predetermined data elements from each study, and a senior scientist reviewed the abstraction. Two experienced reviewers independently appraised the quality of each study using published Laboratory Medicine Best Practices (LMBP™) A-6 scoring criteria. We assessed the body of evidence using the A-6 methodology, and the evidence suggested that electronic tools or one-on-one education increased documentation of pending tests in discharge summaries. We also found that automated notifications improved awareness of TPAD. The interventions were supported by suggestive evidence; this type of evidence is below the level of evidence required for LMBP™ recommendations. We encourage additional research into the impact of these interventions on key processes and health outcomes.

Genetic contributions to urgency urinary incontinence in women.

PURPOSE: We identify genetic variants associated with urgency urinary incontinence in postmenopausal women. MATERIALS AND METHODS: A 2-stage genome-wide association analysis was conducted to identify variants associated with urgency urinary incontinence. The WHI GARNET substudy with 4,894 genotyped post-reproductive white women was randomly split into independent discovery and replication cohorts. Genome-wide imputation was performed using IMPUTE2 with the 1000 Genomes ALL Phase I integrated variant set as a reference. Controls reported no urgency urinary incontinence at enrollment or followup. Cases reported monthly or greater urgency urinary incontinence and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict urgency urinary incontinence case vs control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates. RESULTS: Following quality control, 975,508 single nucleotide polymorphisms in 2,241 cases (discovery 1,102; replication 1,133) and 776 controls (discovery 405, replication 371) remained. Genotype imputation resulted in 9,077,347 single nucleotide polymorphisms and insertions/deletions with minor allele frequency greater than 0.01 available for analysis. Meta-analysis of the discovery and replication samples identified 6 loci on chromosomes 5, 10, 11, 12 and 18 associated with urgency urinary incontinence at p <10(-6). Of the loci 3 were within genes, the zinc finger protein 521 (ZFP521) gene on chromosome 18q11, the ADAMTS16 gene on chromosome 5p15 and the CIT gene on chromosome 12q24. The other 3 loci were intergenic. CONCLUSIONS: Although environmental factors also likely contribute, this first exploratory genome-wide association study for urgency urinary incontinence suggests that genetic variants in the ZFP521, CIT and ADAMTS16 genes might account for some of the observed heritability of the condition.

Communicating risk of hereditary breast and ovarian cancer with an interactive decision support tool.

OBJECTIVE: Women with hereditary breast and ovarian cancer syndrome (HBOC) face a higher risk of earlier, more aggressive cancer. Because of HBOC's rarity, screening is recommended only for women with strong cancer family histories. However, most patients do not have accurate history available and struggle to understand genetic concepts. METHODS: Cancer in the Family, an online clinical decision support tool, calculated women's HBOC risk and promoted shared patient-provider decisions about screening. A pilot evaluation (n=9 providers, n=48 patients) assessed the tool's impact on knowledge, attitudes, and screening decisions. Patients used the tool before wellness exams and completed three surveys. Providers accessed the tool during exams, completed exam checklists, and completed four surveys. RESULTS: Patients entered complete family histories (67%), calculated personal risk (96%), and shared risk printouts with providers (65%). HBOC knowledge increased dramatically for patients and providers, and many patients (75%) perceived tool results as valid. The tool prompted patient-provider discussions about HBOC risk and cancer family history (88%). CONCLUSIONS: The tool was effective in increasing knowledge, collecting family history, and sparking patient-provider discussions about HBOC screening. PRACTICE IMPLICATIONS: Interactive tools can effectively communicate personalized risk and promote shared decisions, but they are not a substitute for patient-provider discussions.

Prenatal counseling on seat belt use and crash-related medical care.

Describe the prevalence of and characteristics associated with being hurt in a car accident during pregnancy; the resulting medical care needed; and the association between counseling and the medical care needed after a car accident. Secondary data analysis of PRAMS (Pregnancy Risk Assessment Monitoring System) data, a population based survey of women with a recent live birth. Two percent of women were hurt in a car accident during their pregnancy. Only 57% of them had received counseling on seat belt use. Most women (87%) who were hurt in an accident needed medical care. Being counseled on seat belt use was not associated with the level of care needed. Most pregnant women who are hurt in a car accident require medical care or bed rest. Public health action and research is needed to reduce the burden of motor-vehicle related injuries among pregnant women.

The PhenX Toolkit pregnancy and birth collections.

PURPOSE: Pregnancy and childbirth are normal conditions, but complications and adverse outcomes are common. Both genetic and environmental factors influence the course of pregnancy. Genetic epidemiologic research into pregnancy outcomes could be strengthened by the use of common measures, which would allow data from different studies to be combined or compared. Here, we introduce perinatal researchers to the PhenX Toolkit and the Collections related to pregnancy and childbirth. METHODS: The Pregnancy and Birth Collections were drawn from measures in the PhenX Tooklit. The lead author selected a list of measures for each Collection, which was reviewed by the remaining authors and revised on the basis of their comments. We chose the measures we thought were most relevant for perinatal research and had been linked most strongly to perinatal outcomes. RESULTS: The Pregnancy and Birth Health Conditions Collection includes 24 measures related to pregnancy and fertility history, maternal complications, and infant complications. The Pregnancy and Birth Outcome Risk Factors Collection includes 43 measures of chemical, medical, psychosocial, and personal factors associated with pregnancy outcomes. CONCLUSIONS: The biological complexity of pregnancy and its sensitivity to environmental and genomic influences suggest that multidisciplinary approaches are needed to generate new insights or practical interventions. To fully exploit new research methods and resources, we encourage the biomedical research community to adopt standard measures to facilitate pooled or meta-analyses.

Women's knowledge, attitudes, and beliefs about Down syndrome: a qualitative research study.

Women who are or may become pregnant need up-to-date information about Down syndrome (DS). Asking women about their knowledge, opinions, resources, and information needs on the topic of DS is an important precursor to develop effective strategies for education. We conducted 24 focus groups (N = 111) in two US cities with women who were recently pregnant (who had a child ≤ 3 years old without DS) and women who planned to have a child in the next year. Groups were further segmented by age and race-ethnicity. Questions explored women's knowledge, attitudes, and beliefs about DS; resources used to obtain information about health and DS; and information needs on the topic of DS. All participants reported having some knowledge of DS: facial features, chromosomal condition, and maternal age as a risk factor. Many participants had misconceptions, including the life expectancy for persons with DS, other maternal and paternal risk factors, and the idea that having a child with DS would disrupt their lives. Participants requested stories to help illustrate what life is like for families with DS. Many Hispanic and African American participants said they only saw or knew of Caucasian persons with DS and requested culturally diverse educational materials about DS. Participants said they would seek information on DS from the Internet and from their health care providers. Results suggest that women need tailored materials that contain clinical information about DS as well as information about living with a child with DS. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

The relationship of socioeconomic status to preterm contractions and preterm delivery.

Spontaneous preterm labor precedes approximately 50% of preterm births. One to 10% of pregnant women are hospitalized for preterm labor. This study examines the relationship of socioeconomic indicators, family income, education and type of insurance, with preterm contractions and subsequent preterm delivery. Data were from the pregnancy risk assessment monitoring system on 107,926 women who had singleton births during 2000-2002. Data on preterm contractions, family income, and type of insurance during pregnancy were from the maternal questionnaire. Maternal education and gestational age were derived from birth certificate data. Predicted marginal probabilities from logistic regression models were used to calculate the adjusted cumulative incidence and cumulative risk ratio of preterm contractions and preterm delivery. Median annual household income was approximately $30,000. More than one-fourth (28.1 95% CI: 27.7, 28.6) of women experienced preterm contractions, and these women were 3 times as likely (18 vs. 5%) to deliver preterm as women without preterm contractions. Only 58% of women who delivered preterm reported contractions. Lower income and Medicaid-paid care were independently associated with an increased risk of preterm contractions but not with preterm delivery. The association of lower income and Medicaid enrollment with preterm contractions but not preterm delivery suggests that SES is associated with the initiation of the pathway to spontaneous preterm delivery rather than access to or the success of interventions to prevent delivery following the onset of contractions.

Birth outcomes of intended pregnancies among women who used assisted reproductive technology, ovulation stimulation, or no treatment.

OBJECTIVE: To study birth outcomes among live born infants conceived by women who used infertility treatment. DESIGN: Population-based surveillance of women who recently delivered a live infant. SETTING: The birth outcomes among infants whose mothers used assisted reproductive technology (ART) or ovulation stimulation medications alone were compared with the outcomes of infants conceived without treatment. PATIENT(S): Stratified random sample of women who were attempting conception and gave birth to a live infant in six US states (n = 16,748). INTERVENTION(S): Assisted reproductive technology and ovulation stimulation. MAIN OUTCOME MEASURE(S): Adjusted odds ratios for perinatal outcomes. RESULT(S): The prevalence of infertility treatment use overall among women attempting conception was 10.9% (5.4% ART procedures, 5.5% ovulation stimulation medications). Singletons of mothers who received ART procedures were more likely to be born with low birthweight, preterm, and small for gestational age (SGA) than singleton infants conceived without treatment. Singleton infants of mothers who used ovulation stimulation medications alone were more likely to be SGA than singleton infants conceived without treatment. No differences were found between ART and no treatment twin infants. CONCLUSION(S): Among singleton infants, ART is associated with decreased fetal growth, decreased gestational length, and SGA; ovulation stimulation alone is associated with SGA.

Racial and ethnic differences in preterm delivery among low-risk women.

BACKGROUND: Preterm delivery is the leading cause of infant mortality in the United States. The risk of preterm delivery and the prevalence of factors associated with preterm delivery differ by racial and ethnic groups. OBJECTIVE: To examine racial and ethnic differences in preterm delivery among women without the common risk factors for preterm delivery. METHODS: We used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) for singleton births occurring in selected US states between 1988 and 2002. PRAMS is a cross-sectional study of state residents who delivered a live birth within the state. We defined risk status using maternal age, education, marital status at delivery, parity, interpregnancy interval, tobacco or alcohol use, source and amount of income, and pre-pregnancy body mass index. RESULTS: Only 9.6% (18,815) of women were low risk. Between 2.4% (Native Americans) and 12.4% (Asian-Pacific Islanders) were low risk. Low-risk women were 29.0% (95% CI: 23.0%, 34.0%) less likely to deliver preterm than non-low-risk women. Among low-risk women, African American women had more preterm births than White women (PR: 1.3, 95% CI: 1.0, 1.6), but only among multiparous women whose most recent prior birth was neither low birth weight nor preterm. CONCLUSIONS: Traditional risk factors explain about half of the excess prevalence of preterm births among African Americans and explain all of the excess among other racial and ethnic groups. The remaining excess among African American appears to be due to risk factors among multiparous women that occur between pregnancies.