Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland. 2011 revision of the Swiss recommendations

Perinatal care of pregnant women at high risk for preterm delivery and of preterm infants born at the limit of viability (22-26 completed weeks of gestation) requires a multidisciplinary approach by an experienced perinatal team. Limited precision in the determination of both gestational age and foetal weight, as well as biological variability may significantly affect the course of action chosen in individual cases. The decisions that must be taken with the pregnant women and on behalf of the preterm infant in this context are complex and have far-reaching consequences. When counselling pregnant women and their partners, neonatologists and obstetricians should provide them with comprehensive information in a sensitive and supportive way to build a basis of trust. The decisions are developed in a continuing dialogue between all parties involved (physicians, midwives, nursing staff and parents) with the principal aim to find solutions that are in the infant's and pregnant woman's best interest. Knowledge of current gestational age-specific mortality and morbidity rates and how they are modified by prenatally known prognostic factors (estimated foetal weight, sex, exposure or nonexposure to antenatal corticosteroids, single or multiple births) as well as the application of accepted ethical principles form the basis for responsible decision-making. Communication between all parties involved plays a central role. The members of the interdisciplinary working group suggest that the care of preterm infants with a gestational age between 22 0/7 and 23 6/7 weeks should generally be limited to palliative care. Obstetric interventions for foetal indications such as Caesarean section delivery are usually not indicated. In selected cases, for example, after 23 weeks of pregnancy have been completed and several of the above mentioned prenatally known prognostic factors are favourable or well informed parents insist on the initiation of life-sustaining therapies, active obstetric interventions for foetal indications and provisional intensive care of the neonate may be reasonable. In preterm infants with a gestational age between 24 0/7 and 24 6/7 weeks, it can be difficult to determine whether the burden of obstetric interventions and neonatal intensive care is justified given the limited chances of success of such a therapy. In such cases, the individual constellation of prenatally known factors which impact on prognosis can be helpful in the decision making process with the parents. In preterm infants with a gestational age between 25 0/7 and 25 6/7 weeks, foetal surveillance, obstetric interventions for foetal indications and neonatal intensive care measures are generally indicated. However, if several prenatally known prognostic factors are unfavourable and the parents agree, primary non-intervention and neonatal palliative care can be considered. All pregnant women with threatening preterm delivery or premature rupture of membranes at the limit of viability must be transferred to a perinatal centre with a level III neonatal intensive care unit no later than 23 0/7 weeks of gestation, unless emergency delivery is indicated. An experienced neonatology team should be involved in all deliveries that take place after 23 0/7 weeks of gestation to help to decide together with the parents if the initiation of intensive care measures appears to be appropriate or if preference should be given to palliative care (i.e., primary non-intervention). In doubtful situations, it can be reasonable to initiate intensive care and to admit the preterm infant to a neonatal intensive care unit (i.e., provisional intensive care). The infant's clinical evolution and additional discussions with the parents will help to clarify whether the life-sustaining therapies should be continued or withdrawn. Life support is continued as long as there is reasonable hope for survival and the infant's burden of intensive care is acceptable. If, on the other hand, the health car...

Determination of ajulemic acid and its glucuronide in human plasma by gas chromatography-mass spectrometry

A method using gas chromatography-mass spectrometry (GC-MS) and solid-phase extraction (SPE) was developed for the determination of ajulemic acid (AJA), a non-psychoactive synthetic cannabinoid with interesting therapeutic potential, in human plasma. When using two calibration graphs, the assay linearity ranged from 10 to 750 ng/ml, and 750 to 3000 ng/ml AJA. The intra- and inter-day precision (R.S.D., %), assessed across the linear ranges of the assay, was between 1.5 and 7.0, and 3.6 and 7.9, respectively. The limit of quantitation (LOQ) was 10 ng/ml. The amount of AJA glucuronide was determined by calculating the difference in the AJA concentration before ("free AJA") and after enzymatic hydrolysis ("total AJA"). The present method was used within a clinical study on 21 patients suffering from neuropathic pain with hyperalgesia and allodynia. For example, plasma levels of 599.4+/-37.2 ng/ml (mean+/-R.S.D., n=9) AJA were obtained for samples taken 2 h after the administration of an oral dose of 20 mg AJA. The mean AJA glucuronide concentration at 2h was 63.8+/-127.9 ng/ml.

Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review

BACKGROUND Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. DATA SOURCES In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. RESULTS We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. DISCUSSION This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.

Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy

This paper reports an LC-MS/MS method with positive electrospray ionization for the screening of commonly prescribed cardiovascular drugs in human plasma, including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO₄ (4:1, v/v) solution after the addition of internal standard, followed by evaporation and reconstitution. Analytes separation was performed on a Polar-RP column (150 m x 2 mm, 4 μm) using a gradient elution of 15 min. The MS system was operated in MRM mode, monitoring one quantitation and one confirmation transition for each analyte. The recovery of the protein precipitation step ranged from 50 to 70% for most of the compounds, while some were considerably affected by matrix effects. Since several analytes fulfilled the linearity, accuracy and precision values required by the ICH guidelines, the method proved to be suitable for their quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 μg/L and the limits of detection from 0.12 to 5.34 μg/L. The method showed to be suitable for the detection of plasma samples of patients under cardiovascular treatment with the studied drugs, and for 55 compounds reliable quantitative results could be obtained.

Uppermost Limit, Extent, and Fluctuations of the Timberline and Treeline Ecocline in the Swiss Central Alps during the past 11,500 Years

Pollen and macrofossils were analyzed at two sites above today's treeline (or tree limit) in the Swiss Central Alps (Gouillé Loéré, 2503 m a.s.l., and Lengi Egga, 2557 m a.s.l.) to test two contrasting hypotheses about the natural formation of timberline (the upper limit of closed forest) in the Alps. Our results revealed that Pinus cembra--Larix decidua forests near timberline were rather closed between 9000 and 2500 B.C. (9600-4000 ¹⁴C yr BP), when timberline fluctuations occurred within a belt 100-150 m above today's tree limit. The treeline ecocline above timberline was characterized by the mixed occurrence of tree, shrub, dwarf-shrub, and herbaceous species, but it did not encompass more than 100-150 altitudinal meters. The uppermost limit reached by timberline and treeline during the Holocene was ca. 2420 and 2530 m, respectively, i.e., about 120 to 180 m higher than today. Between 3500 and 2500 B.C. (4700-4000 ¹⁴C yr BP) timberline progressively sank by about 300 m, while treeline was lowered only ca. 100 m. This change led to an enlargement of the treeline-ecocline belt (by ca. 300 m) after 2500 B.C. (4000 ¹⁴C yr BP). Above the treeline ecocline, natural meadows dominated by dwarf shrubs (e.g., Salix herbacea) and herbaceous species (e.g., Helianthemum, Taraxacum, Potentialla, Leontodon t., Cerastium alpinum t., Cirsium spinosissimum, Silene exscapa t., and Saxifraga stellaris) have been present since at least 11,000 cal yr ago. In these meadows tree and tall shrub species (>0.5 m) never played a major role. These results support the conventional hypothesis of a narrow ecocline with rather sharp upper timberline and treeline boundaries and imply that today's treeless alpine communities in the Alps are close to a natural stage. Pollen (percentages and influx), stomata, and charcoal data may be useful for determining whether or not a site was treeless. Nevertheless, a reliable and detailed record of past local vegetation near and above timberline is best achieved through the inclusion of macrofossil analysis.