Prediction of small-for-gestational-age neonate by third-trimester fetal biometry and impact of ultrasound-delivery interval.

OBJECTIVES: To compare third-trimester ultrasound screening methods to predict small-for-gestational age (SGA), and to evaluate the impact of the ultrasound-delivery interval on screening performance. METHODS: In this prospective study, data were collected from a multicenter singleton cohort study investigating the links between various exposures during pregnancy with birth outcome and later health in children. We included women, recruited in the first trimester, who had complete outcome data and had undergone third-trimester ultrasound examination. Demographic, clinical and biological variables were also collected from both parents. We compared prediction of delivery of a SGA neonate (birth weight < 10th percentile) by the following methods: abdominal circumference (AC) Z-score based on Hadlock curves (Hadlock AC), on INTERGROWTH-21st Project curves (Intergrowth AC) and on Salomon curves (Salomon AC); estimated fetal weight (EFW) Z-score based on Hadlock curves (Hadlock EFW) and on customized curves from Gardosi (Gardosi EFW); and fetal growth velocity based on change in AC between second and third trimesters (FGVAC). We also assessed the following ultrasound-delivery intervals: ≤ 4 weeks, ≤ 6 weeks and ≤ 10 weeks. RESULTS: Third-trimester ultrasound was performed in 1805 patients with complete outcome data, of whom 158 (8.8%) delivered a SGA neonate. Ultrasound examination was at a median gestational age of 32 (interquartile range, 31-33) weeks. The ultrasound-delivery interval was ≤ 4 weeks in 17.2% of cases, ≤ 6 weeks in 48.1% of cases and ≤ 10 weeks in 97.3% of cases. Areas under the receiver-operating characteristics curve (AUC) were 0.772 for Salomon AC, 0.768 for Hadlock EFW, 0.766 for Hadlock AC, 0.765 for Intergrowth AC, 0.708 for Gardosi EFW and 0.674 for FGVAC (all P < 0.0001). The screening method with the highest AUC for an ultrasound-delivery interval ≤ 4 weeks was Salomon AC (AUC, 0.856), ≤ 6 weeks was Hadlock AC (AUC, 0.824) and ≤ 10 weeks was Salomon AC (AUC, 0.780). At a fixed 10% false-positive rate, the best detection rates were 60.0%, 54.1% and 42.1% for intervals ≤ 4, ≤ 6 and ≤ 10 weeks, respectively. CONCLUSION: Third-trimester ultrasound measurements provide poor to moderate prediction of SGA. A shorter ultrasound-delivery interval provides better prediction than does a longer interval. Further studies are needed to test the effect of including maternal or biological characteristics in SGA screening. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of neonatal outcome of TTTS by fetal heart and Doppler ultrasound parameters before and after laser treatment.

OBJECTIVES: To determine the prognostic value of fetal Doppler and echocardiographic parameters for neonatal survival up to 30 days after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS). METHODS: Fetal echocardiography and outcome data of consecutive cases of TTTS treated by laser were retrospectively reviewed. Hemodynamic and cardiac function parameters were collected before and after laser. RESULTS: Between February 2006 and January 2015, 106 fetoscopic laser were performed. The final analysis was limited to cases with ultrasound within 2 days before laser (n = 77) and 4 weeks after laser (n = 86). Overall neonatal survival rate was 64.9% (135/208) and 77.9% of pregnancies (81/104) had at least one baby alive. For the recipient twin, the preoperative predictors of neonatal survival were umbilical artery (UA) pulsatility index (PI), cerebro-placental PI ratio, UA end diastolic flow (EDF), ductus venosus a-wave, right ventricular myocardial performance index (RV-MPI) and CHOP score. The postoperative predictors of donor survival were donor RV-MPI and recipient UA EDF, umbilical vein pulsations, tricuspid regurgitation, cardiac hypertrophy and CHOP score. CONCLUSION: The hemodynamic predictors of postnatal survival after laser were preoperative signs of recipient cardiomyopathy and postoperative signs of cardiac overload in both twins. © 2016 John Wiley & Sons, Ltd.

Prevalence of rosacea in the general population of Germany and Russia - The RISE study.

BACKGROUND: There is an unmet need for general population-based epidemiological data on rosacea based on contemporary diagnostic criteria and validated population survey methodology. OBJECTIVE: To evaluate the prevalence of rosacea in the general population of Germany and Russia. METHODS: General population screening was conducted in 9-10 cities per country to ensure adequate geographic representation. In Part I of this two-phase study, screening of a representative sample of the general population (every fifth person or every fifth door using a fixed-step procedure on a random route sample) was expedited with use of a questionnaire and algorithm based on current diagnostic criteria for rosacea. Of the subjects that screened positive in the initial phase, a randomly selected sample (every third subject) t`hen underwent diagnostic confirmation by a dermatologist in Part II. RESULTS: A total of 3052 and 3013 subjects (aged 18-65 years) were screened in Germany and Russia respectively. Rosacea prevalence was 12.3% [95%CI, 10.2-14.4] in Germany and 5.0% [95%CI, 2.8-7.2] in Russia. The profile of subjects with rosacea (75% women; mean age of 40 years; mainly skin phototype II or III, majority of subjects with sensitive facial skin) and subtype distribution were similar. Overall, 18% of subjects diagnosed with rosacea were aged 18-30 years. Over 80% were not previously diagnosed. Within the previous year, 47.5% of subjects had received no rosacea care and 23.7% had received topical and/or systemic drugs. Over one-third (35% Germany, 43% Russia) of rosacea subjects reported a moderate to severe adverse impact on quality of life. CONCLUSION: Rosacea is highly prevalent in Germany (12.3%) and Russia (5.0%). The demographic profile of rosacea subjects was similar between countries and the majority were previously undiagnosed.

A treatment for severe nodular acne: a randomized investigator-blinded, controlled, noninferiority trial comparing fixed-dose adapalene/benzoyl peroxide plus doxycycline vs. oral isotretinoin.

BACKGROUND: Oral isotretinoin (ISO) is the gold standard for severe nodular acne. However, as some patients are unwilling or unable to take, or are intolerant to, ISO, other options are needed. OBJECTIVES: To compare efficacy and safety of oral ISO vs. doxycycline 200 mg plus adapalene 0·1%/benzoyl peroxide 2·5% gel (D+A/BPO) in severe nodular acne over 20 weeks. METHODS: This was a multicentre, randomized, controlled, noninferiority investigator-blinded study involving 266 subjects. RESULTS: D+A/BPO showed a significantly earlier onset of action in reducing nodules, papules/pustules and total lesions at week 2. ISO was superior in reducing nodules (95·6% vs. 88·7%), papules/pustules (95·2% vs. 79·6%) and total lesions (92·9% vs. 78·2%; all P < 0·01) at week 20. Half as many subjects for D+A/BPO compared with ISO had treatment-related, medically relevant adverse events (33 events in 18·0% of subjects vs. 73 in 33·8% of subjects, respectively). D+A/BPO was noninferior to ISO in the intent-to-treat population [95% confidence interval (CI) -2·7 to 20·8 (P = 0·13); 63·9% vs. 54·9% of subjects, respectively] and per-protocol population [95% CI 3·9-28·6 (P = 0·01); 74·3% vs. 58% of subjects, respectively), based on the composite efficacy/safety end point. CONCLUSIONS: D+A/BPO showed a favourable composite efficacy/safety profile compared with ISO. This combination is an alternative to ISO in patients intolerant to, or unable or unwilling to take, oral ISO, and is an option for treatment of severe nodular acne.

Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia.

OBJECTIVE: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Seventeen urban obstetric hospitals, Canada. POPULATION: Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of pre-eclampsia. Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). METHODS: Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12-18 and 24-26 weeks of gestation using chemiluminescence immunoassay. MAIN OUTCOME MEASURES: Pre-eclampsia. RESULTS: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24-26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24-26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37-7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12-18 weeks of gestation. CONCLUSIONS: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia.

Comparison of two different sites of measurement for transabdominal uterine artery Doppler velocimetry at 11-13 weeks.

OBJECTIVES: To compare the feasibility of two transabdominal approaches for performing first-trimester uterine artery (UtA) Doppler and to evaluate the correlation with pulsatility index (PI) in the second trimester. METHODS: This was a prospective longitudinal Doppler study of the uterine arteries at 11-13 and 21-22 weeks' gestation. Transabdominal ultrasound and color Doppler were used to measure the UtA-PI of the ascending branch of the uterine artery at the level of the internal cervical os (Site A) and at the level of the apparent crossover with the external iliac artery (Site B) at 11-13 weeks, and at Site B only at 21-22 weeks. In all cases the measured left and right PI were converted to a multiple of the median (MoM) for gestational age, and the intercorrelation between the measurements at different sites and gestational ages was calculated using non-parametric analysis (Spearman's rank correlation). RESULTS: Satisfactory measurements were obtained at 11-13 weeks from both uterine arteries in all 81 women at Site A and in 50 (62%; 95% CI, 50-72%) at Site B (P < 0.01). Measurements were obtained at Site B at 21-22 weeks in all cases. In the 50 cases with measurements from both sites at 11-13 weeks, the correlation of PI-MoMs between Sites A and B at 11-13 weeks was only moderate (ρ = 0.61). The correlation between first-trimester UtA-PI MoMs at Site A and second-trimester UtA-PI MoMs was stronger than that between first-trimester UtA-PI MoMs at Site B and second-trimester UtA-PI MoMs (ρ = 0.73 vs ρ = 0.47, P < 0.01). CONCLUSION: Evaluation of UtA-PI at 11-13 weeks can be achieved at the level of the internal cervical os in a greater proportion of women than at the level of the apparent crossover with the external iliac vessels, and the measurements obtained correlate better with second-trimester UtA-PI.

Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.

The protective immunogenicity of a hybrid peptide containing tandem copies of types 5 and 24 epitopes was investigated. Carboxy-terminal peptides of the cyanogen bromide-derived fragment 7 (CB7) of type 24 M protein were chemically synthesized, and then extended to include the first 20 residues of the amino-terminus of type 5 M protein. When emulsified in CFA and injected into rabbits without conjugation to a carrier, each of the synthetic hybrid peptides, designated S-M5(1-20)-S-CB7(23-35)C and S-M5(1-20)-S-CB(19-34), evoked opsonic antibodies against both types 5 and 24 streptococci without raising heart tissue-crossreactive immunity. These results suggest that tandem hybrid peptides may provide a new approach to the development of multivalent vaccines, not only to different serotypes of group A streptococci but perhaps also to a variety of other infectious agents.

Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry.

OBJECTIVES: To establish whether reagent-supported thrombelastometry with the rotation thrombelastometry system (ROTEM) point-of-care device correlated with fibrinogen level in postpartum haemorrhages. DESIGN: Prospective observational study. POPULATION AND SETTING: Ninety-one women at the third trimester of pregnancy: 37 with postpartum haemorrhage (study group) and 54 without abnormal bleeding (control group). METHODS: Standard laboratory test results were compared with those obtained at bedside from the ROTEM with the FIBTEM test (54 tests in the control group and 51 in the study group). MAIN OUTCOME MEASURES: Analysis of correlations between fibrinogen levels and FIBTEM test results: clotting time (CT), clot amplitude at 5 and 15 minutes (CA5; CA15) and maximal amplitude [maximum clot firmness (MCF)]. RESULTS: Median fibrinogen level was significantly lower in the haemorrhage group than in the control group (3.4 and 5.1 g/l, respectively, P < 0.0001). Median CT was higher in the haemorrhage group than in the control group (P = 0.05). CA5, CA15 and MCF were significantly lower in the haemorrhage group than in controls (P < 0.0001) and strongly correlated with fibrinogen levels in both groups (r = 0.84-0.87, P < 0.0001). A cut-off value of CA5 at 5 mm and CA15 at 6 mm presented an excellent sensitivity (100% for both parameters) and a good specificity (respectively 85 and 88%) to detect fibrinogen levels <1.5 g/l in postpartum haemorrhage. Conclusions The early parameters obtained from the FIBTEM test correlated well with fibrinogen levels. ROTEM might be helpful in guiding fibrinogen transfusion during postpartum haemorrhage.

[Fellowship in Canada: instructions]. / Fellowship au Canada : mode d'emploi.

In North America, postdoctoral fellowships are proposed to physicians and surgeons after their residency to obtain an expertise in a specific domain of their speciality. In obstetrics and gynecology, three fellowship programs are accredited by the Royal College of Physicians and Surgeons of Canada: maternal fetal medicine, gynaecological oncology and reproductive endocrinology and infertility. A two-year fellowship in Canada provides a great professional and personal experience. We present here the organization of these programs and the conditions to be admitted in a fellowship program in Canada.

[Duration of pushing in labor: literature review]. / Durée des efforts expulsifs: données de la littérature.

French guidelines recommend performing an assisted delivery after 30min pushing, even if the fetal heart rate is reassuring. A literature review shows that international practices differ from French recommendations; primiparous women usually push on average one hour. Specific data about duration of the active second stage are scarce. Therefore, there is no evidence that maternal and neonatal outcome would be improved by an early-assisted delivery as compared to pushing efforts prolonged after 30min.

[Evaluation of the third trimester amniocentesis for fetal karyotyping in women with fear of pregnancy loss]. / Evaluation de l'amniocentèse au troisième trimestre pour le dépistage des anomalies chromosomiques chez les patientes n'acceptant pas le risque de perte foetale.

OBJECTIVES: The aim of this study is to determine the complications of third trimester amniocentesis for fetal karyotyping among women unwilling to accept the fetal loss risks of second trimester amniocentesis. MATERIALS AND METHODS: A retrospective study was carried out from January 1998 to December 2006 of 182 singleton pregnancies that underwent a late amniocentesis (after 32 weeks) for fetal karyotyping. The indications were integrated risk (maternal age, first trimester nuchal translucency, second trimester maternal serum markers) over 1/250 (n=68), isolated maternal age over 38 years (n=51), isolated abnormal second trimester biochemical markers (n=34), history of personal or familial a chromosomal abnormality (n=21) or maternal choice (n=8). Presence of fetal abnormalities at ultrasound or context of viral or parasitologic seroconversion as well as multiple pregnancies were considered as non-inclusion criteria. RESULTS: Median maternal age and gestational age at sampling were 39 years (range 23-48) and 32.4 weeks (29.5-37.6). Median interval between amniocentesis and definitive results of amniocentesis on the one hand, and delivery on the on the hand were 15 days (7-42) and 47 days (8-69), respectively. There were no chromosomal abnormality and non-termination of pregnancy. Nine patients out of 182(5%) had a spontaneous labour followed by premature delivery before 37 weeks and six women (3.3%) among those nine displayed preterm premature rupture of membranes (PPROM). Four patients out of 182 (2%) gave birth before definitive karyotyping result but all of them had a direct fluorescence in situ hybridisation analysis with a normal karyotyping result known well before delivery. CONCLUSIONS: The risk of preterm premature rupture of membrane is 3.3%, with a 5% risk of premature delivery before 37 weeks. This late procedure provides a safe reassurance to women who are unwilling to accept the risks of earlier amniocentesis. However, it should only be used in particular situation and in countries were legislation allows late termination of pregnancy.

[Tocolysis with calcium-channel blockers and intraventricular hemorrhage]. / Tocolyse par les inhibiteurs calciques et hémorragies intraventriculaires.

OBJECTIVE: To determine the possible association between intraventricular hemorrhage (IVH) in very premature infants and calcium-channel blockers used as tocolytics. MATERIALS AND METHODS: We performed a case-control study (from October 1999 to December 2002) including 51 premature infants under 30 weeks with IVH (all grade) and 112 premature infants under 30 weeks without IVH. In this study only premature infants issued from spontaneous prematurity were included. The exposure frequency to calcium-channel blockers and to other tocolytics were compared between the two groups by univariate analysis and by logistic regression analysis. RESULTS: Calcium-channel blockers were used in monotherapy before birth in 16% of infants without IVH and in 20% of infants with IVH (P=0.55). An exposure to a bitherapy or a tritherapy with a calcium-channel blocker and one or several other tocolytics has been found in 43% of infants with IVH and in 26% of infants without IVH (P<0.05). However this association disappears after adjustment for gestational age. CONCLUSION: We did not find a significant association between calcium-channel blockers used as tocolytics and an increased risk of intraventricular hemorrhage in premature infants less than 30 weeks.

Tracing the origins of "fetal origins" of adult diseases: programming by oxidative stress?

Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" of disease phenomenon remain unresolved. Too large size at birth seems also associated with an increased risk. Many known or suspected causes of or conditions associated with adverse (poor or excessive) fetal growth or preterm birth have been associated with oxidative stress. Plausibly, oxidative stress may be a common link underlying the superficial "programming" associations between adverse fetal growth or preterm birth and elevated risks of certain chronic diseases. The mechanisms of oxidative stress programming may be through directly modulating gene expression or indirectly through the effects of certain oxidized molecules. Experimental investigations have well demonstrated the role of redox balance in modulating gene expression, and recent studies indicate that both the insulin functional axis and blood pressure could be sensitive targets to oxidative stress programming. Adverse programming may occur without affecting fetal growth, but more frequently among low birth weight infants merely because they more frequently experienced known or unknown conditions with oxidative insults. As oxidative stress levels are easily modifiable during pregnancy and early postnatal periods (which are plausible critical windows), the hypothesis, if proved valid, will suggest new measures that could be very helpful on fighting the increasing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Currently, there are several ongoing large randomized trials of antioxidant supplementation to counter oxidative stress during pregnancy for the prevention of preeclampsia. It would be invaluable if long-term follow-ups of infants born to women in such trials could be realized to test the oxidative stress programming hypothesis in such experimental trial settings.

Synthetic peptide vaccines against pathogens and biological mediators.

Recent advances in immunology and biotechnology have opened the way for new approaches to vaccine design. Gilles Riveau and Françoise Audibert discuss progress in the design of synthetic peptide antigens for vaccines against pathogens, and discuss the possibility that such vaccines could also be used to control the activity of endogenous mediators.

Adjuvants: current status, clinical perspectives and future prospects.

Adjuvants represent a key issue for vaccines currently under development. Adjuvanticity is linked to the ability to stimulate the T-cell subsets that control the major features of specific immune responses: CD4+ TH1 and TH2 cells and CD8+ cells involved in cytotoxic T-lymphocyte responses. Some well-defined immunomodulatory compounds can achieve this stimulation by inducing selective production of appropriate cytokines. Françoise Audibert and Luc Lise review the development of adjuvants and discuss how their combination with suitable vehicles should allow customization of adjuvant preparations capable of inducing protective immune responses better adapted to each type of pathogenicity.