Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.

BACKGROUND: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome. AIM: To characterize the skin microbiome in a series of patients with DEB. METHODS: This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools. RESULTS: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin. CONCLUSIONS: These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.

Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes.

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Characteristics of women with nausea and vomiting of pregnancy who chose to continue compassionate use of placebo after a randomised trial.

The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.

Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.

Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were approximately 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.

Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery.

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.

Consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes.

OBJECTIVE: To test the hypothesis that, in women with type 1 diabetes, prenatal smoking and caffeine consumption during pregnancy are associated with an increased risk of adverse maternal and perinatal outcomes. METHODS: A secondary analysis of data on pregnant women with type 1 diabetes from an interdisciplinary program of Diabetes in Pregnancy. Women were interviewed monthly, by a trained non-medical member of the research team, using a standardized questionnaire, to ascertain daily smoking habits and caffeine consumption. RESULTS: Smoking and caffeine information were available on 191 pregnancies, 168 progressing beyond 20 weeks of gestation. Early pregnancy smoking (OR 3.3, 95% CI 1.2, 8.7) and caffeine consumption (OR 4.5, 95% CI 1.2, 16.8) were associated with increased risk of spontaneous abortion when controlling for age, years since diagnosis of diabetes, previous spontaneous abortion, nephropathy and retinopathy. Smoking throughout pregnancy was significantly associated with decreased birth weight and prolonged neonatal hospital stay. Smoking throughout pregnancy (OR 0.2, 95% 0.1, 1.0) and caffeine consumption after 20 weeks (OR 0.3, 95% CI 0.1, 1.0) were associated with reduced risk of pre-eclampsia. CONCLUSIONS: Caffeine consumption during early pregnancy, regardless of glycemic control, increases the risk of spontaneous abortion. Smoking throughout pregnancy and caffeine consumption are associated with reduced risk of pre-eclampsia.

A planned randomized clinical trial of treatment for mild gestational diabetes mellitus.

OBJECTIVE: A planned study is described which will determine whether a benefit exists for the treatment of mild carbohydrate intolerance during pregnancy. METHODS: A randomized clinical trial of women with mild gestational diabetes will compare perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. RESULTS: The primary outcome of this study will be a composite of neonatal morbidity in the treatment and control groups. CONCLUSIONS: A randomized treatment trial of mild gestational diabetes mellitus will clarify whether identification and treatment of mild gestational diabetes mellitus reduces perinatal morbidity. This information will aid in selecting appropriate thresholds for the treatment of gestational diabetes mellitus.

Is the use of insulin lispro safe in pregnancy?

OBJECTIVE: To provide a review of the use and safety of insulin lispro during pregnancy. METHODS: This is a review of the available literature on the use of insulin lispro in pregnancy. A MEDLINE search was performed which included published manuscripts and abstracts in the English language to June 2001. RESULTS: The extensive search revealed that data on insulin lispro use during pregnancy are limited. Most of the reports on the use of insulin lispro during pregnancy demonstrated improvement of glycemic control, an increase in patient satisfaction, decreased hypoglycemic episodes, improved maternal and neonatal outcomes, and no deterioration in retinal status. However, there were two reports where it was suggested that there was an association with the use of insulin lispro in pregnancy and increased risk for the development of congenital anomalies and/or development or progression of diabetic retinopathy. CONCLUSIONS: Preliminary data suggest that insulin lispro does not have adverse maternal or fetal effects during pregnancy in women with diabetes. The use of insulin lispro during pregnancy results in improved glycemic control, fewer hypoglycemic episodes, improved patient satisfaction, improved maternal and neonatal outcomes and no deterioration in retinal status. There is no evidence that the use of insulin lispro during pregnancy results in an increased rate of congenital malformations. A prospective randomized clinical trial is imperative for further evaluation of any possible association with the use of insulin lispro during pregnancy and an increased rate of congenital malformations or change in retinal status.

Pregnancy outcome and progression of diabetic nephropathy. What's next?

OBJECTIVES: The first objective was to assess the association of renal function with maternal and fetal pregnancy outcome in women with diabetic nephropathy. The second objective was to examine the feasibility of a multicenter surveillance program to determine the rates of maternal and fetal pregnancy complications in women with diabetic nephropathy, and to study the effect of pregnancy on the natural history of diabetic renal disease. METHODS: In order to address the first objective, we analyzed data from women with type 1 diabetes and nephropathy enrolled in the Diabetes in Pregnancy Program at our institution. Women were assigned to one of three groups according to enrolment serum creatinine concentration: < or = 1.0 mg/dl, > 1.0 to 1.5 mg/dl and > 1.5 mg/dl. A pilot surveillance program at six centers included women experiencing pregnancy complicated by diabetic nephropathy. In both studies, medical and obstetric history, and maternal and neonatal outcomes, were recorded. Statistical analysis included chi2, logistic regression and analysis of variance. RESULTS: There were 72 pregnancies in 58 women with diabetic nephropathy who enrolled in the pregnancy program. High serum creatinine concentration at enrolment was associated with delivery before 32 weeks' gestation, very low birth weight and increased incidence of neonatal hypoglycemia, independent of quantity of total urinary protein excretion and glycemic control in any trimester. To date, pilot surveillance data have been obtained from six centers on 16 women. Serum creatinine concentrations ranged from 0.4 to 1.1 mg/dl and creatinine clearance from 32 to 317 m/min. Gestational age at delivery ranged from 22 to 39 weeks. CONCLUSIONS: High serum creatinine concentration at enrolment is a risk factor for adverse maternal and neonatal outcome, independent of quantity of total urinary protein excretion and glycemic control during any trimester. A multicenter surveillance program is needed, in order to study less frequent maternal and neonatal outcomes as well as the long-term effects of pregnancy on the natural course of diabetic renal disease.

Spontaneous preterm delivery in the type 1 diabetic pregnancy: the role of glycemic control.

OBJECTIVE: To determine the role of glycemic control in spontaneous preterm delivery in type 1 diabetic women. METHODS: A secondary analysis of data from women enrolled in the Diabetes in Pregnancy Program prior to 20 weeks was performed. Multiple logistic regression was used to analyze the association between glycohemoglobin A1 in women with spontaneous preterm delivery (n = 53) and women who delivered at term (n = 200). Maternal demographics and obstetric outcomes were also compared between the groups. RESULTS: Glycohemoglobin A1 levels were higher in the spontaneous preterm delivery group than the term group throughout pregnancy, reaching statistical significance after the first trimester. The last glycohemoglobin A1 prior to delivery was 8.1% in the spontaneous preterm delivery group and 7.4% in the term group (p = 0.002). Using multiple logistic regression, each 1% increase in glycohemoglobin A1 increased the risk of spontaneous preterm delivery by 37%. CONCLUSION: Poor glycemic control is associated with an increased risk of spontaneous preterm delivery, suggesting that strict glycemic control may reduce the rate of preterm delivery in these women.

Intrapartum fetal head position I: comparison between transvaginal digital examination and transabdominal ultrasound assessment during the active stage of labor.

OBJECTIVE: To test the null hypothesis that no correlation exists between transvaginal digital and the gold standard technique of transabdominal suprapubic ultrasound assessments of fetal head position during labor. A secondary objective was to compare the performance of attending physicians vs. senior residents in depicting fetal head position by transvaginal digital examination in comparison with ultrasound, respectively. METHODS: Consecutive patients in active labor at term with normal singleton cephalic-presenting fetuses were included. All participants had ruptured membranes, cervical dilation > or = 4 cm and fetal head at ischial spine station -2 or lower. Transvaginal sterile digital examinations were performed by either senior residents or attending physicians and followed immediately by transverse suprapubic transabdominal ultrasound assessments. Examiners were blinded to each other's findings. Power-analyses dictated number of subjects required. Statistical analyses included Chi-square, Cohen's Kappa test and logistic regression analysis. P < 0.05 was considered statistically significant. RESULTS: One hundred and two patients were studied (n = 102). In only 24% of patients (n = 24), transvaginal digital examinations were consistent with ultrasound assessments (P = 0.002, 95% confidence interval, 16-33). Logistic regression revealed that cervical effacement (P = 0.03) and ischial spine station (P = 0.01) significantly affected the accuracy of transvaginal digital examination. Parity, gestational age, combined spinal epidural anesthesia, cervical dilation, birth weight and examiner experience did not significantly affect accuracy of the examination. The accuracy of the transvaginal digital exams was increased to 47% (n = 48) (95% confidence interval, 37-57) when fetal head position at transvaginal digital examination was recorded as correct if reported within +/- 45 degrees of the ultrasound assessment. The rate of agreement between the two assessment methods for attending physicians vs. residents was 58% vs. 33%, respectively (P = 0.02) with the +/- 45 degrees analysis. CONCLUSIONS: Using ultrasound assessment as the gold standard, our data demonstrate an overall high rate of error (76%) in transvaginal digital determination of fetal head position during active labor, consistent with the null hypothesis. Attending physicians exhibited an almost two-fold higher success rate in depicting correct fetal head position by physical examination vs. residents in the +/- 45 degrees analysis. Intrapartum ultrasound increases the accuracy of fetal head position assessment during active labor and may serve as an educational tool for physicians in training.

Intrapartum fetal head position II: comparison between transvaginal digital examination and transabdominal ultrasound assessment during the second stage of labor.

OBJECTIVE: To test the null hypothesis that no correlation exists between transvaginal digital examination compared with the gold standard technique of transabdominal suprapubic ultrasound assessment of fetal head position during the second stage of labor. A secondary objective was to compare the performance of attending physicians vs. senior residents in depicting fetal head position by transvaginal digital examination in comparison with ultrasound assessment. METHODS: Consecutive patients in the second-stage of labor at term with normal singleton cephalic-presenting fetuses and ruptured membranes were included. Transvaginal digital examinations were performed by either attending physicians or senior residents and were followed immediately by transverse suprapubic transabdominal sonographic assessments performed by a single sonographer. Examiners were blinded to each other's findings. Power analysis dictated sample size. Exact binomial confidence intervals around observed rates were compared with chi 2 and Cohen's kappa-tests. Logistic regression was applied. P < 0.05 was considered significant throughout. RESULTS: One hundred and twelve patients were studied. The absolute error of transvaginal digital examinations was recorded in 65% of patients (95% confidence interval, 56-74%). Parity, pelvic station, combined spinal epidural anesthesia, length of first or second stages of labor, use of oxytocin augmentation, gestational age, mode of delivery, birth weight, and examiner experience did not significantly affect examination accuracy. Stratification, when the transvaginal digital examination was recorded as correct if occurring within +/- 45 degrees of the ultrasound assessment, reduced the error of the transvaginal digital examinations to 39% (95% confidence interval, 30-49%). Independent variables again did not affect examination accuracy in this assessment modality. Rates of agreement between the two methods for attending physicians compared with residents were not significantly different. The overall degrees of agreement were 40% (95% confidence interval, 26-55%) and 68% (95% confidence interval, 53-80%) (kappa = 0.25 and 0.30) for the absolute agreement and +/- 45 degrees assessment modalities, respectively, for attending physicians, and 31% (95% confidence interval, 20-44%) and 55% (95% confidence interval, 42-68%) (kappa = 0.14 and 0.12) for senior residents. CONCLUSION: Using ultrasound assessment as the gold standard, our data demonstrate a high rate of error (65%) in transvaginal digital determination of fetal head position during the second stage of labor. The performance of senior residents in transvaginal digital examinations did not differ significantly from that of attending physicians. Intrapartum ultrasound increases the accuracy of fetal head position assessment during the second stage of labor.

The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. RESULTS: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th 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. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P < .002). With the use of only the 3 serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test 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.