First trimester "clean catch" urine and vaginal swab sample distinct microbiological niches.

IMPORTANCE: Untreated asymptomatic bacteriuria (ASB) has been associated with adverse pregnancy outcomes, including pyelonephritis, preterm labor, and low birth weight infants. Thus, routine screening by standard urine culture (SUC) and treatment of ASB are currently recommended for all pregnant women. For this purpose, some researchers claim that vaginal swabs and urine samples can be used as proxies for each other. Because SUC often misses microbes, we used two more sensitive, recently validated detection methods to compare the composition of the urinary and vaginal microbiomes of pregnant females in their first trimester. Both methods yielded similar results. Vaginal and urinary microbial compositions for the same individual were significantly correlated; however, they were not equivalent. We argue that first trimester urinary and vaginal microbiomes are distinct enough to preclude their use as proxies for each other.

Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study.

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study.

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58-3.77) and MMA% (aOR = 1.95 (95% CI 0.81-4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25-1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

An evaluation of nutritional and vasoactive stimulants as risk factors for gastroschisis: a pilot study.

OBJECTIVE: The objective of this study is to evaluate poor maternal nutrition, environmental exposures and vasoactive stimulants as potential risk factors for gastroschisis. METHODS: A case-control study was conducted among singleton pregnancies diagnosed in a tertiary teaching hospital in a 22-month period. Cases of gastroschisis were matched to controls at the time of diagnosis by race and maternal age. Demographics, periconceptual exposures, nutritional biomarkers, and illicit drug hair analysis were evaluated. Analyses were performed using conditional logistic regression. RESULTS: Thirty gastroschisis cases and 76 controls were studied with no associations observed for illicit drug use or serum levels of ferritin, iron, B6, B12, folate, or zinc. Neither prescription medication nor over the counter mediation use differed between cases and controls. Following adjustment for insurance, education, low BMI, and nulliparity, mothers of gastroschisis cases had an increased odds of alcohol use 1 month prior and/or during early pregnancy compared with controls, with adjusted odds ratio (OR) 3.19 (95% CI 1.01-11.61). CONCLUSIONS: Our findings suggest that further investigation of vasoactive stimulants such as alcohol is warranted in the search to identify risk factors for gastroschisis.

A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent preterm birth.

OBJECTIVE: To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone for prevention of recurrent preterm birth. METHODS: A prospective randomized controlled trial was conducted at a US tertiary care center between June 1, 2007, and April 30, 2010. Women with singleton pregnancies (16-20 weeks) and a history of spontaneous preterm birth were randomly allocated using a computer-generated randomization sequence to receive either a weekly intramuscular injection of hydroxyprogesterone caproate (250 mg) or a daily vaginal progesterone suppository (100 mg). Participants, investigators, and assessors were not masked to group assignment. The primary outcome was birth before 37 weeks of pregnancy. Per-protocol analyses were performed: participants who completed follow-up were included. RESULTS: Analyses included 66 women given intramuscular progesterone and 79 given vaginal progesterone. Delivery before 37 weeks was recorded among 29 (43.9%) women in the intramuscular progesterone group and 30 (37.9%) in the vaginal progesterone group (P=0.50). CONCLUSION: Weekly intramuscular administration of hydroxyprogesterone caproate and daily vaginal administration of a progesterone suppository exhibited similar efficacy in reducing the rate of recurrent preterm birth. ClinicalTrials.gov: NCT00579553.

Epidemiology of Dysglycemia in Pregnant Oklahoma American Indian Women.

CONTEXT: Minority communities are disproportionately affected by diabetes, and minority women are at an increased risk for glucose intolerance (dysglycemia) during pregnancy. OBJECTIVES: In pregnant American Indian women, the objectives of the study were to use current criteria to estimate the prevalence of first-trimester (Tr1) dysglycemia and second-trimester (Tr2) incidence of gestational diabetes mellitus (GDM) and to explore new candidate measures and identify associated clinical factors. DESIGN: This was a prospective cohort study. In Tr1 we performed a 75-g, 2-hour oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) to determine the following: fasting insulin; homeostasis model assessment of insulin resistance; serum 1,5-anhydroglucitol; noninvasive skin autofluorescence (SCOUT). We defined dysglycemia by American Diabetes Association and Endocrine Society criteria and as HbA1c of 5.7% or greater. In Tr2 in an available subset, we performed a repeat OGTT and SCOUT. PARTICIPANTS: Pregnant American Indian women (n = 244 at Tr1; n = 114 at Tr2) participated in the study. OUTCOMES: The prevalence of dysglycemia at Tr1 and incidence of GDM at Tr2 were measured. RESULTS: At Tr1, one woman had overt diabetes; 36 (15%) had impaired glucose tolerance (American Diabetes Association criteria and/or abnormal HbA1c) and 59 (24%) had GDM-Tr1 (Endocrine Society criteria). Overall, 74 (30%) had some form of dysglycemia. Associated factors were body mass index, hypertension, waist/hip circumferences, SCOUT score, fasting insulin, and homeostasis model assessment of insulin resistance. At Tr2, 114 of the Tr1 cohort underwent a repeat OGTT and SCOUT, and 26 (23%) had GDM. GDM-Tr2 was associated with increased SCOUT scores (P = .029) and Tr1 body mass index, waist/hip circumferences, diastolic blood pressure, fasting insulin, and triglyceride levels. Overall, dysglycemia at Tr1 and/or Tr2 affected 38% of the women. CONCLUSIONS: Dysglycemia at some point during pregnancy was common among American Indian women. It was associated with features of insulin resistance and may confer long-term health risks for mother and child.

Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy.

PURPOSE: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). METHODS: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. RESULTS: Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥ 3 rd tertile) of mono-iso-butyl phthalate (tertile: ≥ 15.3 µg/l, ß = -18.3, 95% CI: -35.4, -1.2) and monobenzyl phthalate (tertile: ≥ 30.3 µg/l, ß = -17.3, 95% CI: -34.1, -0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. CONCLUSION: Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously.

Is bisphenol-A exposure during pregnancy associated with blood glucose levels or diagnosis of gestational diabetes?

Recent epidemiological studies indicate bisphenol A (BPA), an estrogenic chemical used in production of epoxy, polycarbonate, and plastic may increase risk of insulin resistance and type 2 diabetes. Exposure to BPA during pregnancy may contribute to development of gestational diabetes mellitus (GDM), a precursor to type 2 diabetes in women. This pilot study examined the association between BPA exposure, fasting blood glucose levels (FBG), and GDM diagnosis during pregnancy. Banked urine samples from 22 cases of GDM and 72 controls were analyzed for total (free BPA + conjugates) urinary BPA concentrations (µg/L). FBG levels (mg/dl) were obtained from 1-h 50-g glucose tolerance tests (GTT) that women underwent for routine GDM screening (mean gestational age = 26.6 weeks, SD = 3.8). Those with an initial screening value ≥ 135 mg/dl underwent 3-h 100 g oral GTT. GDM diagnoses were made when the initial screening value was ≥ 200 mg/dl or when values at ≥ 2 time points exceeded 3-h oral GTT thresholds. Among controls, median FBG levels (mg/dL) did not differ across exposure tertiles, defined according to the distribution of total specific-gravity-adjusted urinary BPA concentrations. Logistic regression models controlling for race/ethnicity did not provide evidence of association between BPA exposure and case status across increasing tertiles of BPA exposure (number of GDM cases/controls in tertile1: 13/24; in tertile 2: 6/24; in tertile 3: 3/24). Findings do not support a relationship between total urinary BPA concentrations and altered glucose metabolism during pregnancy. However, due to study limitations, findings need to be interpreted with caution.

Local anesthesia and pain perception during amniocentesis: a randomized double blind placebo-controlled trial.

OBJECTIVE: To determine the effect of local anesthesia on the maternal pain perception from amniocentesis. METHODS: We conducted a randomized double blind placebo controlled trial comparing use of local anesthesia (1% lidocaine) with placebo with regards to maternal perception of pain among women undergoing genetic amniocentesis. The primary outcome was the intensity of perceived maternal pain as measured by the Visual Analogue Scale (VAS) as well a 101 point Numerical Rating Scale. RESULTS: Seventy six women participated in the trial. 36 (47.4%) women were randomized to lidocaine, whereas 40 (52.6%) were randomized to placebo. There were no statistically significant differences between the groups in terms of baseline sociodemographic and clinical characteristics. However, pain perception as characterized by the median 9.5 (2.1-21.0) VSA scores was significantly lower among women in the lidocaine group compared with among women in the placebo group [18.4 (12.9-31.3), P = 0.005]. Similarly the mean VSA scores was significantly lower in the lidocaine group (P = 0.02). A trend toward lower scores was also observed when maternal pain perception was measured by the Numerical Rating Scale. CONCLUSION: Local anesthetic lidocaine significantly lowers maternal perceived pain during genetic amniocentesis.

Unsuccessful trial of labor in women with and without previous cesarean delivery.

OBJECTIVE: To compare maternal and neonatal outcomes after unsuccessful labor in women with and those without prior cesarean delivery. METHODS: This was a retrospective cohort study of all women in labor delivered by cesarean section (CS) from November 2004 through December 2006. The study population was dichotomized by previous CS and compared for various maternal and neonatal outcomes. Student t-test, χ² and Fisher exact tests were used for analysis. RESULTS: There was a significantly higher rate of symptomatic uterine rupture [3/100 (3%) vs. 0/449 (0%), p = 0.006], asymptomatic uterine scar dehiscence [6/100 (6%) vs. 0/449 (0%), p = 0.0001], and bladder injury [2/100 (2%) vs. 0/100 (0%), p = 0.001], among women with prior cesarean delivery compared to those without. The rate of respiratory distress syndrome [(6/100) (6%) vs. 10/449 (2.2%), p = 0.05] and meconium aspiration [4/100 (4%) vs. 2/449 (0.4%), p = 0.01] was also significantly higher among neonates of women with prior cesarean delivery. However, the rate of endomyometritis [3/100 (3%) vs. 50/449 (11.1%), p = 0.009] and febrile morbidity [17/100 (17%) vs. 144/449 (32.1%), p  = 0.003] was significantly lower among women with prior cesarean delivery compared to those without prior cesarean birth. CONCLUSIONS: Compared to laboring women without previous cesarean delivery, women with previous cesarean delivery have increased maternal and neonatal morbidity. Febrile morbidity was, however, lower among women with previous cesarean delivery. These differential findings should further inform our perinatal counseling of women contemplating trial of labor after a previous cesarean delivery.

The effect of digital cervical examination on group B streptococcal culture.

OBJECTIVE: We sought to evaluate whether group B streptococcus (GBS) detection is altered by the digital cervical examination. STUDY DESIGN: A total of 302 women undergoing the clinical GBS culture had a digital cervical examination and a repeated GBS culture. Statistical comparison of pre-post culture results were performed with kappa and McNemar tests. RESULTS: The clinical prevalence of GBS was 19.5%. Discordant results were seen in 30/302 (9.9%) paired cultures (kappa = 0.68; 95% confidence interval, 0.568-0.783). An initially negative GBS culture result was positive on repeated testing in 13/243 (5.3%) pairs. Initially positive cultures were negative on repeated testing in 17/59 (28.8%) pairs. Patients with discordant results had similar characteristics as the remainder of the study group. Given the observed proportion of discordant results (9.9%), the study had 80% power to detect a 5% difference between discordant pairs. CONCLUSION: Paired GBS cultures showed a good level of agreement. The 28.8% rate of positive cultures becoming negative is clinically concerning and warrants further study.

Prenatal identification of a novel R937P L1CAM missense mutation.

The L1 cell adhesion molecule (L1CAM) is a protein encoded by a gene that has been localized to Xq28, is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules, and plays a role in CNS development and maturation. L1CAM is expressed in neurons and Schwann cells, where it is active in neurite overgrowth, adhesion fasciculation, migration, myelination, and axon guidance. Mutations within the gene have been associated with phenotypic changes that include hydrocephalus due to aqueductal stenosis, agenesis or hypoplasia of the corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. Here, we present a 19-year-old primigravida Caucasian woman who was referred to us in the 27th week of the pregnancy because of fetal polyhydramnios and ventriculomegaly. Our evaluation identified a male fetus with hydrocephalus, ventriculomegaly, aqueductal stenosis, and polyhydramnios. An amniocentesis was performed, and isolated fetal DNA revealed a hemizygous G > C mutation in codon 2809 of exon 21 of the L1CAM gene. The patient was later tested and identified to be a carrier of the same mutation. The fetus was delivered during the 38th week. Neonatal physical examination revealed marked frontal bossing, contractures of the feet with rocker bottom appearance, and hyperactive reflexes with ankle and knee clonus. He died at 4 months of life.

Etiological heterogeneity of familial periventricular heterotopia and hydrocephalus.

Periventricular heterotopia (PH) represents a neuronal migration disorder that results in gray matter nodules along the lateral ventricles beneath an otherwise normal appearing cortex. While prior reports have shown that mutations in the filamin A (FLNA) gene can cause X-linked dominant PH, an increasing number of studies suggest the existence of additional PH syndromes. Further classification of these cortical malformation syndromes associated with PH allows for determination of the causal genes. Here we report three familial cases of PH with hydrocephalus. One pedigree has a known FLNA mutation with hydrocephalus occurring in the setting of valproic acid exposure. Another pedigree demonstrated possible linkage to the Xq28 locus including FLNA, although uncharacteristically a male was affected and sequencing of the FLNA gene in this individual revealed no mutation. However, in the third family with an autosomal mode of inheritance, microsatellite analysis ruled out linkage with the FLNA gene. Routine karyotyping and fluorescent in situ hybridization using BAC probes localized to FLNA also showed no evidence of genomic rearrangement. Western blot analysis of one of the affected individuals demonstrated normal expression of the FLNA protein. Lastly, sequencing of greater than 95% of the FLNA gene in an affected member failed to demonstrate a mutation. In conclusion, these findings demonstrate the etiological heterogeneity of PH with hydrocephalus. Furthermore, there likely exists an autosomal PH gene, distinct from the previously described X-linked and autosomal recessive forms. Affected individuals have severe developmental delay and may have radiographic findings of hydrocephalus.