Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proα1(I) and proα2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype-phenotype relationships emerge for each chain. Onethird of the mutations that result in glycine substitutions in α1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691-823 and 910-964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibrilmatrix interactions. Recurrences at the same site in α2(I) are generally concordant for outcome, unlike α1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In α2(I), lethal exon skipping events are located in the carboxyl half of the chain. Our data on genotype-phenotype relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events.

Objective-To describe contemporary cesarean delivery practice in the U.S.Study Design-Consortium on Safe Labor collected detailed labor and delivery information from 228,668 electronic medical records from 19 hospitals across the U.S., 2002 -2008. Results-The overall cesarean delivery rate was 30.5%. 31.2% of nulliparas were delivered by cesarean section. Prelabor repeat cesarean delivery due to a previous uterine scar contributed 30.9% of all cesarean sections. 28.8% of women with a uterine scar had a trial of labor and the success rate Corresponding author: Dr. Jun Zhang, Epidemiology Branch, NICHD, National Institutes of Health, Building 6100, Room 7B03, Bethesda, MD 20892, Tel: 301-435-6921, zhangj@mail.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptAm J Obstet Gynecol. Author manuscript; available in PMC 2011 October 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript was 57.1%. 43.8% women attempting vaginal delivery had induction. Half of cesarean for dystocia in induced labor were performed before 6 cm of cervical dilation.Conclusion-To decrease cesarean delivery rate in the U.S., reducing primary cesarean delivery is the key. Increasing VBAC rate is urgently needed. Cesarean section for dystocia should be avoided before the active phase is established, particularly in nulliparas and in induced labor.

Objective-To use contemporary labor data to examine the labor patterns in a large, modern obstetric population in the United States.Methods-Data were from the Consortium on Safe Labor, a multicenter retrospective study that abstracted detailed labor and delivery information from electronic medical records in 19 hospitals across the United States. A total of 62,415 parturients were selected who had a singleton term gestation, spontaneous onset of labor, vertex presentation, vaginal delivery, and a normal perinatal outcome. A repeated-measures analysis was used to construct average labor curves by parity. An interval-censored regression was used to estimate duration of labor stratified by cervical dilation at admission and centimeter by centimeter. Results-Labor may take over 6 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm of dilation. Nulliparas and multiparas appeared to progress at a similar pace before 6 cm. However, after 6 cm labor accelerated much faster in multiparas than in nulliparas. The 95 th percentile of the 2 nd stage of labor in nulliparas with and without epidural analgesia was 3.6 and 2.8 hours, respectively. A partogram for nulliparas is proposed.Conclusion-In a large, contemporary population, the rate of cervical dilation accelerated after 6 cm and progress from 4 to 6 cm was far slower than previously described. Allowing labor to continue for a longer period before 6 cm of cervical dilation may reduce the rate of intrapartum and subsequent repeat cesarean deliveries in the United States.