James Troendle

Contemporary cesarean delivery practice in the United States

OBJECTIVE To describe contemporary cesarean delivery practice in the United States. STUDY DESIGN Consortium on Safe Labor collected detailed labor and delivery information from 228,668 electronic medical records from 19 hospitals across the United States, 2002-2008. RESULTS The overall cesarean delivery rate was 30.5%. The 31.2% of nulliparous women were delivered by cesarean section. Prelabor repeat cesarean delivery due to a previous uterine scar contributed 30.9% of all cesarean sections. The 28.8% of women with a uterine scar had a trial of labor and the success rate was 57.1%. The 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 United States, reducing primary cesarean delivery is the key. Increasing vaginal birth after previous cesarean rate is urgently needed. Cesarean section for dystocia should be avoided before the active phase is established, particularly in nulliparous women and in induced labor.

Contemporary Patterns of Spontaneous Labor With Normal Neonatal Outcomes

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 95th 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. LEVEL OF EVIDENCE: III

Controlling the number of false discoveries: application to high-dimensional genomic data

Abstract Researchers conducting gene expression microarray experiments often are interested in identifying genes that are differentially expressed between two groups of specimens. A straightforward approach to the identification of such “differentially expressed” genes is to perform a univariate analysis of group mean differences for each gene, and then identify those genes that are most statistically significant. However, with the large number of genes typically represented on a microarray, using nominal significance levels (unadjusted for the multiple comparisons) will lead to the identification of many genes that truly are not differentially expressed, “false discoveries.” A reasonable strategy in many situations is to allow a small number of false discoveries, or a small proportion of the identified genes to be false discoveries. Although previous work has considered control for the expected proportion of false discoveries (commonly known as the false discovery rate), we show that these methods may be inadequate. We propose two stepwise permutation-based procedures to control with specified confidence the actual number of false discoveries and approximately the actual proportion of false discoveries. Limited simulation studies demonstrate substantial gain in sensitivity to detect truly differentially expressed genes even when allowing as few as one or two false discoveries. We apply these new methods to analyze a microarray data set consisting of measurements on approximately 9000 genes in paired tumor specimens, collected both before and after chemotherapy on 20 breast cancer patients. The methods described are broadly applicable to the problem of identifying which variables of any large set of measured variables differ between pre-specified groups.

Genetic Defects and Clinical Characteristics of Patients with a Form of Oculocutaneous Albinism (Hermansky–Pudlak Syndrome)

BACKGROUND Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. METHODS Forty-nine patients -- 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent -- were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication. RESULTS Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age. CONCLUSIONS The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults.

Labor progression and risk of cesarean delivery in electively induced nulliparas

OBJECTIVE: To describe the pattern of labor progression and risk of cesarean delivery in women whose labor was electively induced. METHODS: We analyzed data on all low-risk, nulliparous women with an elective induction or spontaneous onset of labor between 37 + 0 and 40 + 6 weeks from January 2002 to March 2004 at a single institution. The median duration of labor by each centimeter of cervical dilation and the risk of cesarean delivery were computed for 143 women with preinduction cervical ripening and oxytocin induction, 286 women with oxytocin induction, and 1,771 women with a spontaneous onset of labor. An intracervical Foley catheter was used to ripen the cervix. RESULTS: Electively induced labor with cervical ripening had substantially slower latent and early active phases. After controlling for potential confounders, women who had an elective induction with cervical ripening had 3.5 times the risk of cesarean delivery during the first stage of labor (95% confidence interval 2.7–4.5), compared with those admitted in spontaneous labor. Elective induction without cervical ripening, on the other hand, was associated with a faster labor progression from 4 to 10 cm (266 compared with 358 minutes, P < .01) and did not increase the risk of cesarean delivery, compared with those in spontaneous labor. CONCLUSION: The pattern of labor progression differs substantially for women with an electively induced labor compared with those with spontaneous onset of labor. Furthermore, elective induction in nulliparous women with an unfavorable cervix has a high rate of labor arrest and a substantially increased risk of cesarean delivery. LEVEL OF EVIDENCE: II-2

Maternal Prepregnancy Overweight and Obesity and the Pattern of Labor Progression in Term Nulliparous Women

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.

Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification

OBJECTIVE. Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B12 is metabolically related to folate; moreover, previous studies have found low B12 status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B12 status on neural tube defect risk in a high-prevalence, unfortified population. METHODS. We assessed pregnancy vitamin B12 status concentrations in blood samples taken at an average of 15 weeks’ gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect–affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects. RESULTS. Mothers of children affected by neural tube defect had significantly lower B12 status. In all 3 groups those in the lowest B12 quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B12 concentrations of <250 ng/L were associated with the highest risks. CONCLUSIONS. Deficient or inadequate maternal vitamin B12 status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B12 levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.

Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted ( approximately 400 mL) per year slower than 10 placebo-treated patients (p=0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC >50% of predicted, both models showed the pirfenidone group losing FVC (p<0.022), FEV(1) (p<0.0007), TLC (p<0.001), and DL(CO) (p<0.122) at a rate approximately 8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function.

Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement.

Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength.

Antibiotic susceptibility profiles for group B streptococci isolated from neonates, 1995-1998

Antibiotic susceptibility profiles were analyzed for 119 invasive and 227 colonizing strains of group B streptococci isolated from neonates at 6 US academic centers. All strains were susceptible to penicillin, vancomycin, chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2% and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V strains were more resistant to erythromycin than were type Ia (P=.003) and type Ib (P=.004) strains and were more resistant to clindamycin than were type Ia (P<.001), type Ib (P=.01), and type III (P=.001) strains. Resistance rates varied with geographic region: in California, there were high rates of resistance to erythromycin and clindamycin (32% and 12%, respectively), and low rates in Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of choice for treatment of group B streptococcus infection. For women who are penicillin intolerant, however, the selection of an alternative antibiotic should be guided by contemporary resistance patterns observed in that region.