The German guideline "Obesity in pregnancy": comparison with the international approach.

BACKGROUND: Obesity is an increasing problem, even in young women of reproductive age. Obesity has a negative impact on conception, the course of pregnancy, and neonatal outcomes. Caring for obese pregnant women has becoming an important aspect of standard prenatal care. The Guideline "Obesity and Pregnancy" of the German Society of Gynecology and Obstetrics aims to create evidence-based recommendations which can be used to improve the care of obese pregnant women. As obesity is a worldwide problem, many societies for obstetrics and gynecology have created national guidelines. METHODS: We reviewed the following guidelines for obesity and pregnancy: American College of Obstetricians and Gynecologists (ACOG) 2021, Royal College of Obstetrics and Gynecology (RCOG) 2018; AND Society of Obstetricians and Gynecologists of Canada (SOGC) 2019. These guidelines were compared to the German guideline. RESULTS: There are some variations between the guidelines, though no major contradictions exist. Disparities were found regarding the recommendations for substitution of high folic acid and Vitamin D. Furthermore, the recommended time for screening for gestational diabetes and the methods to control fetal growth differ between the guidelines. Regarding place of birth, RCOG allows delivery in midwifery-led units in the absence of other high-risk circumstances, while others request facility of care by neonatologists and medical staff trained in care of obese women. Induction of labor at term due to increased risk of intrauterine demise is mostly limited to women with a body mass index of 40 kg/m2. Only one guideline considers induction of all obese women. For intrapartum management, the majority allows tolerating of longer labor times to delivery if fetal monitoring is sufficient and fetal stress is excluded. Special encouragement of breastfeeding and healthy lifestyle is commonly recommended; only in the Canadian guideline, postpartum depression evaluation is requested due to the overall high prevalence of depression and anxiety in obese women. CONCLUSION: All guidelines consider pregnancies in obese women as high-risk pregnancies and emphasize the need for preconception counseling. There are special needs in pregnancy care and in the intrapartum and postpartum management to be observed.

Performance of a chirped-pulse Fourier transform millimeter wave spectrometer in the range of 75-110 GHz.

We present a home-built chirped-pulse Fourier transform millimeter wave (CP-FTMMW) spectrometer. The setup is devoted to the sensitive recording of high-resolution molecular spectroscopy in the W band between 75 and 110 GHz. We describe the experimental setup in detail, including a characterization of the chirp excitation source, the optical beam path, and the receiver. The receiver is a further development of our 100 GHz emission spectrometer. The spectrometer is equipped with a pulsed jet expansion and a DC discharge. Spectra of methyl cyanide as well as hydrogen cyanide (HCN) and hydrogen isocyanide (HNC) products from the DC discharge of this molecule are recorded to characterize the performance of the CP-FTMMW instrument. The formation of the HCN isomer is favored by a factor of 63 with respect to HNC. Hot/cold calibration measurements enable a direct comparison of the signal and noise levels of the CP-FTMMW spectra to those of the emission spectrometer. For the CP-FTMMW instrument, we find many orders of magnitude of signal enhancement and a much stronger noise reduction due to the coherent detection scheme.

Need for less tight glucose control in early pregnancy after embryogenesis due to high risk of maternal hypoglycaemia in women with pre-existing diabetes can be compensated by good control in late pregnancy.

AIM: Poor glucose control is associated with adverse outcomes in pregnancies with pre-existing diabetes. However, strict glucose control increases the risk of severe hypoglycaemia, particularly in the first trimester. Therefore, we aimed to investigate whether less tight glucose control in the first trimester determines adverse outcomes or can be compensated for by good control in late pregnancy. METHODS: Retrospective data were collected from 517 singleton pregnancies complicated by pre-existing diabetes delivering between 2010 and 2017. Three hundred and thirty-six pregnancies fulfilled the inclusion criteria of having available HbA1c values either pre-conception or in the first trimester (65% type 1 diabetes, 35% type 2 diabetes). RESULTS: Higher HbA1c values in the first trimester were associated with increasing rates of large for gestational age (LGA) neonates, preterm delivery or neonatal intensive care unit admissions. Multiple regression analysis demonstrated third trimester HbA1c , type 1 diabetes, multiparity and excess weight gain, but not first trimester HbA1c , to be independently predictive for LGA. Pre-eclampsia and third trimester HbA1c increased the risk for preterm delivery. If HbA1c was ≤ 42 mmol/mol (6.0%) in the third trimester, rates of adverse outcomes were not significantly higher even if HbA1c targets of ≤ 48 mmol/mol (6.5%) had not been met in the first trimester. Good first trimester glucose control did not modify the rates of adverse outcomes if HbA1c was > 42 mmol/mol (6.0%) in the third trimester. CONCLUSIONS: Less tight glycaemic control, for example due to high frequency of severe hypoglycaemia in the first trimester, does not lead to increased adverse neonatal events if followed by tight control in the third trimester. Besides glycaemic control, excess weight gain is a modifiable predictor of adverse outcome.

Higher rates of large-for-gestational-age newborns mediated by excess maternal weight gain in pregnancies with Type 1 diabetes and use of continuous subcutaneous insulin infusion vs multiple dose insulin injection.

AIMS: To compare glycaemic control, maternal and neonatal outcomes in pregnancies with Type 1 diabetes, managed either by continuous subcutaneous insulin infusion, multiple daily insulin injection or switch from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) in early pregnancy. RESEARCH DESIGN AND METHODS: Data from 339 singleton pregnancies were retrospectively reviewed. HbA1c values were measured preconception and in each trimester. In a secondary analysis, use of CSII pre-pregnancy was compared with initiation of CSII during pregnancy. RESULTS: MDI was used in 140 pregnancies (41.3%) and CSII was used in 199 (58.7%), including 34 pregnancies (10.0%) during which the women switched to CSII. In pregnancies during which CSII was used duration of diabetes [median (interquartile range) 16.0 (8.0-23.0) years vs 11.0 (5.5-17.5) years; P<0.001] was longer, and the Institute of Medicine recommendations for appropriate weight gain were exceeded more often (64.8% vs. 50.8%; P=0.01). CSII use and pre-pregnancy BMI were independent predictors of excess weight gain. There was no difference in glucose control, but CSII was associated with higher birth weight [median (interquartile range) 3720 (3365-4100) g vs 3360 (3365-4100) g; P<0.001] and higher large-for-gestational-age (LGA) rate (44.7% vs. 33.6%; P=0.04) than MDI. HbA1c concentration in the third trimester and excess weight gain were predictive of LGA infants [odds ratio 2.33 (95% CI 1.54-3.51); P<0.001 and 1.89 (95% CI 1.02-3.51); P=0.04]. In pregnancies where CSII therapy was initiated in the first trimester and in those with pre-pregnancy use, similar glucose control and outcome was achieved. CONCLUSIONS: There was no advantage of CSII with respect to glycaemic control and neonatal outcomes. The rate of LGA neonates was higher in the CSII group, possibly mediated by excess maternal weight gain, which was more frequent than in women treated with MDI.

Disruption of the Orion molecular core 1 by wind from the massive star θ1 Orionis C.

Massive stars inject mechanical and radiative energy into the surrounding environment, which stirs it up, heats the gas, produces cloud and intercloud phases in the interstellar medium, and disrupts molecular clouds (the birth sites of new stars1,2). Stellar winds, supernova explosions and ionization by ultraviolet photons control the lifetimes of molecular clouds3-7. Theoretical studies predict that momentum injection by radiation should dominate that by stellar winds8, but this has been difficult to assess observationally. Velocity-resolved large-scale images in the fine-structure line of ionized carbon ([C II]) provide an observational diagnostic for the radiative energy input and the dynamics of the interstellar medium around massive stars. Here we report observations of a one-square-degree region (about 7 parsecs in diameter) of Orion molecular core 1-the region nearest to Earth that exhibits massive-star formation-at a resolution of 16 arcseconds (0.03 parsecs) in the [C II] line at 1.9 terahertz (158 micrometres). The results reveal that the stellar wind originating from the massive star θ1 Orionis C has swept up the surrounding material to create a 'bubble' roughly four parsecs in diameter with a 2,600-solar-mass shell, which is expanding at 13 kilometres per second. This finding demonstrates that the mechanical energy from the stellar wind is converted very efficiently into kinetic energy of the shell and causes more disruption of the Orion molecular core 1 than do photo-ionization and evaporation or future supernova explosions.

A laboratory heterodyne emission spectrometer at submillimeter wavelengths.

We present first results on a newly built broadband emission spectrometer for the laboratory making use of a double sideband (DSB) heterodyne receiver. The new spectrometer is perfectly suited for high-resolution emission spectroscopy of molecules of astrophysical importance. The current SIS receiver operates at RF frequencies between 270 and 390 GHz, coincident with Band 7 of the ALMA telescope. The instantaneous bandwidth is 5 GHz (DSB). In this work the full spectrometer and its components are described. Its performance, in particular its sensitivity, stability, reproducibility and systematic errors, is characterized in detail. For this purpose very broad band emission spectra of methyl cyanide have been recorded and compared to theoretical spectra. Isotopic variants are found in natural abundance and features attributed to vibrationally excited species are all recorded in the same spectrum. The performance of the new spectrometer is compared extensively to that of a traditional FM-absorption spectrometer and to recent versions of chirped-pulse spectrometers operated in the mm-wave regime. Further applications and future advancements of the current instrument are discussed.

Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications.

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.

[Predisposition and phenotypes of gestational diabetes]. / Prädisposition und Phänotypen des Gestationsdiabetes.

Gestational diabetes (GDM) is defined as glucose intolerance first diagnosed with a 75 gram oral glucose tolerance test based on IADPSG criteria which had been recently adopted by WHO. In industrial countries GDM is one of the most frequent pregnancy complications. In 2012, in Germany GDM had been diagnosed in 4,3 % of all births, overall 27,700 cases. GDM has to be considered as a preliminary stage of type 2 diabetes with insulin resistance and inadequate ß-cell-compensation. Additionally, adverse metabolic profile, associations with inflammatory parameters, with D vitamin metabolism, and insufficient decline of renal threshold for glucose had been identified in women with GDM. Within 10 years after GDM roughly 50 % of the women convert to overt diabetes, mostly type 2. GDM and type 2 diabetes share potential candidate genes. In about 1 % of GDM in Caucasian women a mutation in glucokinase gene had been found (GCK-MODY). Predisposition to GDM is predominantly characterized by family history of diabetes, previous GDM in pregnancies, factors of metabolic syndrome, and unfavorable life style. The probability for GDM rises with increasing mother's age and preconceptional BMI. Via fetal programming GDM dispones to offspring obesity as early as school entry. Prevention of GDM focus on regular physical exercise, normalizing body weight before conception, reducing excess intake of animal protein and soft drinks, planning of pregnancy in younger ages, and avoiding pollutant exposition as well as smoking cessation.

Differences in the implications of maternal lipids on fetal metabolism and growth between gestational diabetes mellitus and control pregnancies.

AIMS: To evaluate the potential contribution of maternal glucose and lipids to fetal metabolic variables and growth in pregnancies with normal glucose tolerance in comparison with pregnancies with well-controlled gestational diabetes previously reported by us. METHODS: In 190 pregnancies with normal oral glucose tolerance tests (controls), insulin, glucose and lipid components were determined in maternal and arterial cord blood serum. Birthweight and neonatal fat mass were obtained after delivery. Values were adjusted for maternal pre-pregnancy BMI, Caesarean section and gestational age. Measurements were compared with those of gestational diabetes previously reported. RESULTS: Maternal serum glucose, triacylglycerol, free fatty acid and cholesterol levels did not differ between control pregnancies and those with gestational diabetes, whereas insulin, homeostasis model assessment and glycerol values were significantly lower in the former (2.6 vs. 5.6 µmol/l and 176 vs. 193 µmol/l, respectively). In contrast, cord blood glucose and free fatty acids were significantly lower in control pregnancies than in those with gestational diabetes (3.9 vs. 4.4 mmol/l and 80.7 vs. 137 µmol/l, respectively); the same was valid for insulin (0.03 vs. 0.05 nmol/l) and homeostasis model assessment (1.0 vs. 1.87). In control pregnancies, maternal serum glucose, free fatty acids and glycerol correlated with those in cord blood, but not with neonatal weight and fat mass, as seen for free fatty acids in those with gestational diabetes. The negative correlation between cord blood triacylglycerols and neonatal weight or fat mass previously reported in gestational diabetes could not be confirmed in control pregnancies, where all fetal lipids showed a positive correlation to neonatal anthropometrics. CONCLUSION: In normal pregnancies, in contrast to those with gestational diabetes, maternal lipids do not influence neonatal weight. Similar levels of maternal lipids in pregnancies with gestational diabetes and control pregnancies, but higher free fatty acids in the cord blood of those with gestational diabetes, indicate their enhanced placental transport and/or enhanced lipolysis as a result of decreased fetal insulin responsiveness.

Sulforaphane modulates the expression of Cyp6a2 and Cyp6g1 in larvae of the ST and HB crosses of the Drosophila wing spot test and is genotoxic in the ST cross.

Constitutive overexpression of Cyp6g1 and Cyp6a2 genes in DDT-resistant line Oregon-flare of the Drosophila melanogaster wing spot test (SMART) has been reported. Cyp6g1 and Cyp6a2 expression levels were compared against the ß-actin gene in the standard (ST) and high bioactivation (HB) crosses of the Somatic Mutation and Recombination test (SMART) treated with sulforaphane or phenobarbital as the control inductor. The CYP450s' enzymatic activity was determined by overall NADH consumption. The expression levels of both genes and the CYP450s activity was higher in the HB cross. The Cyp6g1 levels were higher than those of Cyp6a2 in both crosses, but lower than the expression of ß-actin. Sulforaphane decreased Cyp6g1 in the HB cross and increased it in the ST cross; Cyp6a2 expression was inhibited in the ST cross. Sulforaphane resulted mutagenic in the ST cross, which could be related to the inhibition of Cyp6a2. Phenobarbital did not modify the Cyp6g1 levels but increased the Cyp6a2 and CYP450s basal activity. Although the transcript levels were always higher in the HB cross than in the ST, the expression of Cyp6a2 and Cyp6g1 was not constitutive and was independent one from the other. Sulforaphane modulated both genes in a differential way in each cross and, in contrast to its putative protective effect, it resulted to be mutagenic.

Route to attosecond nonlinear spectroscopy.

We demonstrate generation of coherent microjoule-scale, low-order harmonic supercontinua in the deep and vacuum ultraviolet (4-9 eV), resulting from the nonlinear transformations of near-single-cycle laser pulses in a gas cell. We show theoretically that their formation is connected to a novel nonlinear regime, holding promise for the generation of powerful deep-UV and vacuum ultraviolet subfemtosecond pulses. Our work opens the route to pump-probe spectroscopy of subfemtosecond-scale valence-shell phenomena in atoms, molecules, and condensed matter.

Follow-up of adult celiac patients: which noninvasive test reflects mucosal status most reliably?1.

UNLABELLED: SPECIFIC AUTHOR CONTRIBUTIONS: Andreas Vécsei, MD, and Ulrike Graf wrote the manuscript. All authors contributed to study design, data collection and analysis, and approved the final draft for submission. The corresponding author declares that the manuscript is submitted on behalf of all authors. BACKGROUND AND STUDY AIMS: The best mode of follow-up in celiac disease has not yet been established. The intention of this study was to clarify which noninvasive follow-up investigation - serological tests or intestinal permeability test (IPT) - correlates best with histology and whether the interval between diagnosis and follow-up affects the accuracy of these tests. PATIENTS AND METHODS: Data from adult patients with celiac disease (diagnosed between December 1989 and July 2006) followed up with biopsy, IPT, and serological tests [IgG anti-gliadin antibodies (AGA-IgG), AGA-IgA, and endomysial antibodies (EMA)] were retrieved from a computerized database. Results of noninvasive tests were compared with the persistence of villous atrophy on biopsy. Patients were divided into groups A, which comprised patients followed up within 2 years after diagnosis, and B, comprising patients followed up later than 2 years. RESULTS: Forty-seven patients were evaluable. The lactulose/mannitol (L/M) ratio had a sensitivity of 85 % and a specificity of 46.2 % for mucosal atrophy, whereas saccharose excretion showed a sensitivity of 60 % and a specificity of 52.6 %. The sensitivities of AGA-IgA and AGA-IgG were 15 % and 20 %, respectively, while specificity was 100 % for both. Validity of AGA was limited due to low number of positive results. EMA assay was 50 % sensitive and 77.8 % specific. In group A (n = 23) L/M ratio performed best in terms of sensitivity (88.9 %), whereas EMA achieved a higher specificity (71.4 %). In group B, the sensitivity of the L/M ratio decreased to 85.7 %, while the specificity of EMA increased to 91.7 %. CONCLUSIONS: In this study, none of the noninvasive tests was an accurate substitute for follow-up biopsy in detecting severe mucosal damage.

Phase locking of a 1.5 Terahertz quantum cascade laser and use as a local oscillator in a heterodyne HEB receiver.

We demonstrate for the first time the closure of an electronic phase lock loop for a continuous-wave quantum cascade laser (QCL) at 1.5 THz. The QCL is operated in a closed cycle cryo cooler. We achieved a frequency stability of better than 100 Hz, limited by the resolution bandwidth of the spectrum analyser. The PLL electronics make use of the intermediate frequency (IF) obtained from a hot electron bolometer (HEB) which is downconverted to a PLL IF of 125 MHz. The coarse selection of the longitudinal mode and the fine tuning is achieved via the bias voltage of the QCL. Within a QCL cavity mode, the free-running QCL shows frequency fluctuations of about 5 MHz, which the PLL circuit is able to control via the Stark-shift of the QCL gain material. Temperature dependent tuning is shown to be nonlinear, and of the order of -16 MHz/K. Additionally we have used the QCL as local oscillator (LO) to pump an HEB and perform, again for the first time at 1.5 THz, a heterodyne experiment, and obtain a receiver noise temperature of 1741 K.

Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.

Propolis is a substance produced by honeybees (Apis mellifera L.). Its components are strong antioxidants and free radical scavengers. The aim of this study was to evaluate the protective effects of a water extract of Brazilian green propolis (WEP) combined with the antitumor agent doxorubicin (DXR) on Drosophila melanogaster wing cells through the somatic mutation and recombination test (SMART). Two different crosses were used: The standard (ST) cross and the high bioactivation (HB) cross. The HB cross is characterized by a constitutively enhanced level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Larvae obtained from these two crosses were chronically treated with different concentrations of WEP (12.5,25.0 and 50.0 mg/mL) alone or combined with DXR (0.125 mg/mL). The results obtained with the two different crosses were rather similar. Neither toxicity nor genotoxicity were observed in WEP treated series. Simultaneous treatment with different concentrations of WEP and DXR led to a reduction in the frequency of recombination compared to the treatment with DXR alone. This anti-recombinogenic effect was proportional to the concentrations applied, indicating a dose-response correlation and can be attributed to the powerful scavenger ability of WEP.

Intense few-cycle light pulses in the deep ultraviolet.

We demonstrate that nonlinear frequency upconversion of few-cycle near-infrared (NIR) laser pulses, by means of harmonic generation in noble gases, is a promising approach for extending cutting-edge, few-cycle ultrafast technology into the deep ultraviolet and beyond, without the need for UV dispersion control. In our experiment, we generate 3.7-fs pulses in the deep UV (approximately 4.6 eV) with adjustable polarization and gigawatt-scale peak power. We demonstrate that the implementation of this concept with a quasi-monocycle driver offers the potential for advancing UV pulse generation towards the 1-fs frontier.

[Severe diabetic fetopathy due to undiagnosed gestational diabetes mellitus]. / Klinik für Geburtsmedizin, Vivantes Klinikum Neukölln, 12351 Berlin. ute.schaefer-graf@vivantes.d

HISTORY AND FINDINGS: A 39 year-old pregnant woman (with one healthy 11 year-old daughter) presented at the antenatal care clinic for routine non-stress test (NST) at the due date. The NST demonstrated normal fetal heart pattern. No anamnestic or clinical risk factors for diabetes during the course of pregnancy were noted in the case file. Ultrasound examinations up to 30 weeks of gestation had shown fetal growth appropriate for gestational age. Two days later, the NST was non-reacting with almost no heart rate variability, indicating an acute fetal risk. While the condition of the fetus was being further assessed by Doppler sonography, a fall in fetal heart rate prompted an emergency section for fetal bradycardia. The male newborn had marked macrosomia (birth weight 5180 g). The pH in umbilical artery blood of 6,77 indicated severe intrauterine hypoxia. Apgar score was 0/1/5. Absence of heart beat and of spontaneous breathing required resuscitation. Echocardiography revealed a hypertrophic cardiomyopathy with dysfunction of the right ventricle and hepatomegaly indicating diabetic fetal pathology. The placenta displayed typical signs of carbohydrate disorder. The maternal 75 g oral glucose tolerance test confirmed the suspicion of maternal diabetes (glucose values 96/210/215 mg/dl). TREATMENT AND COURSE: During the next the day the infant developed multi-organ failure involving the liver and kidneys, myocardial infarction with pericardial effusion and myoclonic seizures. His condition improved slowly under measures to stabilize the circulation, substitution of clotting factors and anticonvulsive therapy. Mechanical ventilation had to be continued for 5 weeks. Examination at 4 months of age revealed marked neurological abnormalities. The mother was referred to a diabetes specialist for further management. CONCLUSION: Undiagnosed and therefore untreated severe gestational diabetes may have fatal consequences for the fetus. Expert committees of obstetricians and diabetes specialists have recommended blood glucose screening between 24 - 28 weeks of gestation of every pregnant woman as part of the routine prenatal care.