James Troendle

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 more than 6 hours to progress from 4 to 5 cm and more than 3 hours to progress from 5 to 6 cm of dilation. Nulliparous and multiparous women appeared to progress at a similar pace before 6 cm. However, after 6 cm, labor accelerated much faster in multiparous than in nulliparous women. The 95 percentiles of the second stage of labor in nulliparous women with and without epidural analgesia were 3.6 and 2.8 hours, respectively. A partogram for nulliparous women is proposed. CONCLUSION: In a large, contemporary population, the rate of cervical dilation accelerated after 6 cm, and progress from 4 cm 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.

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 proalpha1(I) and proalpha2(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. One-third of the mutations that result in glycine substitutions in alpha1(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 fibril-matrix interactions. Recurrences at the same site in alpha2(I) are generally concordant for outcome, unlike alpha1(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 alpha2(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.

CONTEXT: Late preterm births (340/7-366/7 weeks) account for an increasing proportion of prematurity-associated short-term morbidities, particularly respiratory, that require specialized care and prolonged neonatal hospital stays. OBJECTIVE: To assess short-term respiratory morbidity in late preterm births compared with term births in a contemporary cohort of deliveries in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective collection of electronic data from 12 institutions (19 hospitals) across the United States on 233,844 deliveries between 2002 and 2008. Charts were abstracted for all neonates with respiratory compromise admitted to a neonatal intensive care unit (NICU), and late preterm births were compared with term births in regard to resuscitation, respiratory support, and respiratory diagnoses. A multivariate logistic regression analysis compared infants at each gestational week, controlling for factors that influence respiratory outcomes. MAIN OUTCOME MEASURES: Respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, respiratory failure, and standard and oscillatory ventilator support. RESULTS: Of 19,334 late preterm births, 7055 (36.5%) were admitted to a NICU and 2032 had respiratory compromise. Of 165,993 term infants, 11,980 (7.2%) were admitted to a NICU, 1874 with respiratory morbidity. The incidence of respiratory distress syndrome was 10.5% (390/3700) for infants born at 34 weeks' gestation vs 0.3% (140/41,764) at 38 weeks. Similarly, incidence of transient tachypnea of the newborn was 6.4% (n = 236) for those born at 34 weeks vs 0.4% (n = 155) at 38 weeks, pneumonia was 1.5% (n = 55) vs 0.1% (n = 62), and respiratory failure was 1.6% (n = 61) vs 0.2% (n = 63). Standard and oscillatory ventilator support had similar patterns. Odds of respiratory distress syndrome decreased with each advancing week of gestation until 38 weeks compared with 39 to 40 weeks (adjusted odds ratio [OR] at 34 weeks, 40.1; 95% confidence interval [CI], 32.0-50.3 and at 38 weeks, 1.1; 95% CI, 0.9-1.4). At 37 weeks, odds of respiratory distress syndrome were greater than at 39 to 40 weeks (adjusted OR, 3.1; 95% CI, 2.5-3.7), but the odds at 38 weeks did not differ from 39 to 40 weeks. Similar patterns were noted for transient tachypnea of the newborn (adjusted OR at 34 weeks, 14.7; 95% CI, 11.7-18.4 and at 38 weeks, 1.0; 95% CI, 0.8-1.2), pneumonia (adjusted OR at 34 weeks, 7.6; 95% CI, 5.2-11.2 and at 38 weeks, 0.9; 95% CI, 0.6-1.2), and respiratory failure (adjusted OR at 34 weeks, 10.5; 95% CI, 6.9-16.1 and at 38 weeks, 1.4; 95% CI, 1.0-1.9). CONCLUSION: In a contemporary cohort, late preterm birth, compared with term delivery, was associated with increased risk of respiratory distress syndrome and other respiratory morbidity.

OBJECTIVE: To examine the effect of maternal overweight and obesity on labor progression. METHODS: We analyzed data from 612 nulliparous women with a term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from 1995 to 2002. The median duration of labor by each centimeter of cervical dilation was computed for normal-weight (body mass index [BMI] 19.8-26.0 kg/m2), overweight (BMI 26.1-29.0 kg/m2), and obese (BMI > 29.0 kg/m2) women and used as a measurement of labor progression. RESULTS: After adjusting for maternal height, labor induction, membrane rupture, oxytocin use, epidural analgesia, net maternal weight gain, and fetal size, the median duration of labor from 4 to 10 cm was significantly longer for both overweight and obese women, compared with normal-weight women (7.5, 7.9, and 6.2 hours, respectively). For overweight women, the prolongation was concentrated around 4-6 cm, whereas for obese women, their labor was significantly slower before 7 cm. CONCLUSION: Labor progression in overweight and obese women was significantly slower than that of normal-weight women before 6 cm of cervical dilation. Given that nearly one half of women of childbearing age are either overweight or obese, it is critical to consider differences in labor progression by maternal prepregnancy BMI before additional interventions are performed.