Longitudinal assessment of spiral and uterine arteries in normal pregnancy using novel ultrasound tool.

OBJECTIVES: To use superb microvascular imaging (SMI) to evaluate longitudinally spiral artery (SA) and uterine artery (UtA) vascular adaptation in normal human pregnancy, and to develop reference ranges for use at various gestational ages throughout pregnancy. METHODS: The data for this study were obtained from the National Institutes of Health (NIH)-funded Human Placenta Project. Women aged 18-35 years, with a body mass index < 30 kg/m2 , without comorbidities, with a singleton gestation conceived spontaneously, and gestational age at or less than 13 + 6 weeks were eligible for inclusion. The current analysis was restricted to uncomplicated pregnancies carried to term. Exclusion criteria included maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation or delivery < 37 weeks. Women who fulfilled the inclusion criteria formed the reference population of the Human Placenta Project study. Each participant underwent eight ultrasound examinations during pregnancy. The pulsatility index (PI) of both the left and right UtA were obtained twice for each artery and the presence or absence of a notch was noted. Using SMI technology, the total number of SA imaged was recorded in a sagittal placental section at the level of cord insertion. The PI and peak systolic velocity (PSV) were also measured in a total of six SA, including two in the central portion of the placenta, two peripherally towards the uterine fundal portion, and two peripherally towards the lower uterine segment. RESULTS: A total of 90 women fulfilled the study criteria. Maternal UtA-PI decreased throughout the first half of pregnancy from a mean ± SD of 1.39 ± 0.50 at 12-13 weeks' gestation to 0.88 ± 0.24 at 20-21 weeks' gestation. The mean number of SA visualized in a sagittal plane of the placenta increased from 8.83 ± 2.37 in the first trimester to 16.99 ± 3.31 in the late-third trimester. The mean SA-PI was 0.57 ± 0.12 in the first trimester and decreased progressively during the second trimester, reaching a nadir of 0.40 ± 0.10 at 24-25 weeks, and remaining constant until the end of pregnancy. SA-PSV was highest in early pregnancy with a mean of 57.16 ± 14.84 cm/s at 12-13 weeks' gestation, declined to a mean of 49.38 ± 17.88 cm/s at 20-21 weeks' gestation and continued to trend downward for the remainder of pregnancy, reaching a nadir of 34.50 ± 15.08 cm/s at 36-37 weeks' gestation. A statistically significant correlation was noted between SA-PI and UtA-PI (r = 0.5633; P < 0.001). Multilevel regression models with natural cubic splines were used to create reference ranges of SA-PSV and SA-PI for given gestational ages. CONCLUSION: From early gestation, we have demonstrated the ability to image and quantify SA blood flow in normal pregnancy, and have developed reference ranges for use at various gestational ages throughout pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

Prospecting potential links between PRRSV infection susceptibility of alveolar macrophages and other respiratory infectious agents present in conventionally reared pigs.

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is one of the main component of the porcine respiratory disease complex (PRDC), which strongly impact the pig production. Although PRRSV is often considered as a primary infection that eases subsequent respiratory coinfections, the possibility that other PRDC components may facilitate PRRSV infection has been largely overlooked. The main cellular targets of PRRSV are respiratory macrophages among them alveolar macrophages (AM) and pulmonary intravascular macrophages (PIM). AM, contrarily to PIM, are directly exposed to the external respiratory environment, among them co-infectious agents. In order to explore the possibility of a co-infections impact on the capacity of respiratory macrophages to replicate PRRSV, we proceed to in vitro infection of AM and PIM sampled from animals presenting different sanitary status, and tested the presence in the respiratory tract of these animals of the most common porcine respiratory pathogens (PCV2, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma floculare, Pasteurella multocida, Bordetella bronchiseptica, Streptoccocus suis). In this exploratory study with a limited number of animals, no statistic differences were observed between AM and PIM susceptibility to in vitro PRRSV infection, nor between AM coming from animals presenting very contrasting respiratory coinfection loads.

Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case-control study.

OBJECTIVE: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). DESIGN: Case-control. SETTING: Three tertiary-care centres across the USA. POPULATION: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. METHODS: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P). MAIN OUTCOME MEASURES: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction). CONCLUSION: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P. TWEETABLE ABSTRACT: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment.

Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies.

OBJECTIVE: To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. METHODS: MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. RESULTS: The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for shoulder dystocia than are non-LGA ones (OR, 7.4 (95% CI, 4.9-9.8) using customized charts; OR, 8.0 (95% CI, 5.3-10.1) using population-based charts). CONCLUSIONS: Both customized and population-based growth charts can identify SGA neonates at risk for adverse outcomes. Although the point estimates of the pooled ORs may differ for some outcomes, the overlapping CIs and lack of direct comparisons prevent conclusions from being drawn on the superiority of one method. Future clinical trials should compare directly the two approaches in the management of fetuses of abnormal size. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Association between gestational weight gain and risk of obesity in preadolescence: a longitudinal study (1997-2007) of 5125 children in Greece.

BACKGROUND: The present study aimed to investigate the association between gestational weight gain (GWG) and birth weight, as well as the body mass index (BMI) status, of children at the ages of 2 and 8 years. METHODS: Population-based data were obtained from a database of all 7-9-year-old Greek children who attended primary school during 1997-2007. The study sample consisted of 5125 children matched with their mothers, randomly selected according to region and place of residence, and equally distributed (approximately 500 per year) throughout the study period (1997-2007). A standardised questionnaire was applied; telephone interviews were carried out to collect maternal age, BMI status at the beginning and the end of pregnancy and GWG, birth weight of offspring and BMI status at the ages of 2 and 8 years, as well as several other pregnancy characteristics (e.g. pregnancy duration, gestational medical problems, maternal smoking and alcohol consumption habits, and lactation of offspring after pregnancy). RESULTS: Gestational weight gain was positively associated with the weight status of offspring at all three life stages studied: newborn (birth weight), infant (BMI) and child (BMI) [b = 0.008 (0.001), b = 0.053 (0.009) and b = 0.034 (0.007), respectively, all P < 0.001], after adjusting for maternal age at pregnancy (significant inverse predictor only at age 2 years). The same applied to excessive GWG, as defined by the Institute of Medicine guidelines. CONCLUSIONS: Excessive GWG was associated with a higher risk of greater infant size at birth and a higher BMI status at the ages of 2 and 8 years. Healthcare providers should encourage women to limit their GWG to the range indicated by the current guidelines.

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

BACKGROUND: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). METHODS: We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. RESULTS: The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. CONCLUSION: Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Expression profiles of fetal membrane nicotinamide adenine dinucleotide phosphate oxidases (NOX) 2 and 3 differentiates spontaneous preterm birth and pPROM pathophysiologies.

INTRODUCTION: Nicotinamide adenine dinucleotide phosphate oxidases (NOX 1-5) are enzymes that generate cellular reactive oxygen species (ROS) besides mitochondria and might be important ROS sources associated with pregnancy complications, particularly preterm premature rupture of membranes (pPROM), that has been related to ROS. OBJECTIVE: To characterize NOX enzymes expression in human fetal membranes. METHODS: Differential expression and localization of NOX isoforms in human fetal membranes collected from women with uncomplicated pregnancies at term, preterm birth (PTB) or pPROM and in vitro in normal term membranes maintained in an organ explant system stimulated with water-soluble cigarette smoke extract (wsCSE) were documented by real time PCR and immunohistochemistry. RESULTS: Fetal membranes from term deliveries, PTB and pPROM expressed NOX 2, 3 and 4 mRNAs whereas NOX 1 and 5 were not detected. NOX 2 expression was 2.3-fold higher in PTB than pPROM (p = 0.005) whereas NOX 3 was 2.2-fold higher in pPROM compared to PTB (p = 0.04). NOX 2 and 3 expressions at term mimicked pPROM and PTB, respectively. No difference in NOX 4 expression was observed among the studied groups. NOX 2, 3 and 4 were localized to both amniotic and chorionic cells. Expression of NOX 2, 3 and 4 were not significant in wsCSE-stimulated membranes compared to untreated controls. DISCUSSION/CONCLUSIONS: NOX enzymes are present in the fetal membranes and are differentially expressed in PTB and pPROM. Absence of any changes in NOXs expression after wsCSE stimulation suggests ROS generation in the membranes does not always correlate with NOX expression.

Reconsidering the switch from low-molecular-weight heparin to unfractionated heparin during pregnancy.

Venous thromboembolic disease accounts for 9% of all maternal deaths in the United States. In patients at risk for thrombosis, common practice is to start prophylactic doses of low-molecular-weight heparin and transition to unfractionated heparin during the third trimester, with the perception that administration of neuraxial anesthesia will be safer while on unfractionated heparin, as spinal/epidural hematomas have been associated with recent use of low-molecular-weight heparin. In patients receiving prophylactic doses of unfractionated heparin, neuraxial anesthesia may be placed, provided the dose used is 5,000 units twice a day. The American Society of Regional Anesthesia and Pain Medicine guidelines recognize that the safety of neuraxial anesthesia in patients receiving more than 10,000 units per day or more than 2 doses per day is unknown, limiting the theoretical benefit of unfractionated heparin at doses higher than 5,000 units twice a day.

Biomarker interactions are better predictors of spontaneous preterm birth.

OBJECTIVE: The objective of this study was to assess the role of biomarker interactions as predictors of spontaneous preterm birth (PTB) using multifactor dimensionality reduction (MDR) analysis. With MDR, a nonparametric, unsupervised, model-free approach, we tested for biomarker interactions within maternal-fetal compartments in 2 racial groups: African Americans (AA) and Caucasians (C). STUDY DESIGN: A total of 36 biomarkers from maternal plasma (MP), cord plasma (CP), and amniotic fluid (AF) were analyzed from 191 patients. The MDR combined attribute selection, construction, and classification to detect biomarker interactions that were assessed for generality and significance using 10× cross-validation and permutation testing. Selected significant interactive models were replicated with additional samples. RESULTS: The interactive model containing interleukin (IL)-2, angiopoietin 2 (ANGPT-2), and IL-6 receptor was significant in AA MP. In AA CP, the IL-8 and tumor necrosis factor (TNF) receptor 1 model was significant. In AA AF, the ANGPT-2 and macrophage inflammatory protein 1 alpha model was significant. Replication of the AA MP model using 54 additional AA MP samples confirmed predictability of these biomarkers. In C AF, interaction was observed between ANGPT-2, monocyte chemotactic protein 3, and TNF-α, but no other interactions were significant in C. CONCLUSIONS: Using MDR, we identified biomarker interactions that are predictors of PTB even in the absence of a main effect with a single biomarker.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

The role of MR cholangiopancreatography in the evaluation of pregnant patients with acute pancreaticobiliary disease.

This study aimed to determine the usefulness of MR cholangiopancreatography (MRCP) in the evaluation of pregnant patients with acute pancreaticobiliary disease and its additional value over ultrasound. MRI studies of pregnant patients who were referred because of acute pancreaticobiliary disease were included. MR images and patient charts were reviewed retrospectively to determine clinical outcome and the results of other imaging studies. 18 pregnant patients underwent MRCP because of right upper quadrant pain (n = 6), pancreatitis (n = 9), cholangitis (n = 1) or jaundice (n = 2). 15 patients were also evaluated with ultrasound. Biliary dilatation was detected in eight patients by ultrasound, but the cause of biliary dilatation could not be determined by ultrasound in seven patients. MRCP demonstrated the aetiology in four of these patients (choledocholithiasis (n = 1), Mirizzi syndrome (n = 1), choledochal cyst (n = 1) and intrahepatic biliary stones (n = 1)) and excluded obstructive pathology in the other four patients. MRCP was unremarkable in the seven patients who had no biliary dilatation on ultrasound. Three patients underwent only MRCP; two had choledocholithiasis and one cholelithiasis and pancreatitis. Choledocholithiasis diagnosed with MRCP (n = 3) was confirmed by endoscopic retrograde cholangiopancreatography. Mirizzi syndrome (n = 1) and a choledochal cyst (n = 1) were confirmed by surgery. The patients with normal MRCP (n = 12) and one patient with intrahepatic stones improved with medical treatment. MRCP appears to be a valuable and safe technique for the evaluation of pregnant patients with acute pancreaticobiliary disease. Especially when ultrasound shows biliary dilatation, MRCP can determine the aetiology and save the patient from unnecessary endoscopic retrograde cholangiopancreatography by excluding a biliary pathology.

Patterns of tobacco use: results from the 2005 Global Youth Tobacco Survey in Lebanon.

We report the results of the 2005 Global Youth Tobacco Survey in Lebanon which investigated the self-reported attitudes and behaviours related to tobacco among 3314 Lebanese schoolchildren aged 13-15 years. Current use of any tobacco product was 60.1%; the use of cigarettes was 10% and other tobacco products 59% with male predominance in all areas. About 80% of students lived in homes where others smoked. About 60% of current smokers wanted to quit smoking and 51% of all students had learned about the effects of tobacco in class. Over a quarter (27%) thought that boys who smoke have more friends and 17% believed that smoking makes boys more attractive. The majority of students had been exposed to both anti-smoking media messages and pro-smoking advertisements.

Patterns of tobacco use: results from the 2005 Global Youth Tobacco Survey in Lebanon

We report the results of the 2005 Global Youth Tobacco Survey in Lebanon which investigated the self-reported attitudes and behaviours related to tobacco among 3314 Lebanese schoolchildren aged 13-15 years. Current use of any tobacco product was 60.1%; the use of cigarettes was 10% and other tobacco products 59% with male predominance in all areas. About 80% of students lived in homes where others smoked. About 60% of current smokers wanted to quit smoking and 51% of all students had learned about the effects of tobacco in class. Over a quarter [27%] thought that boys who smoke have more friends and 17% believed that smoking makes boys more attractive. The majority of students had been exposed to both anti-smoking media messages and pro-smoking advertisements