Non-invasive prenatal testing (NIPT): Europe's first multicenter post-market clinical follow-up study validating the quality in clinical routine.

PURPOSE: Non-invasive prenatal tests (NIPT) for the determination of fetal aneuploidies from maternal blood are firmly established in clinical routine. For the first time, the accuracy of an NIPT for the determination of trisomies 21, 18 and 13 in singleton pregnancies was assessed by means of a prospective German-wide multicenter post-market clinical follow-up study, to reliably evaluate the quality in clinical routine. METHODS: The study covered the indications for testing, the test results, the rate of invasive diagnostics and the pregnancy outcome. 2232 cases were tested for trisomy 21. Of these, 1946 cases were additionally examined for trisomy 18 and 13. RESULTS: Sensitivity and specificity for trisomy 21 (43/43) and for trisomy 13 (2/2) were 100%, for trisomy 18 the sensitivity was 80% (4/5) with a specificity of 99.8%. Three false-positive results for trisomy 18 were observed (FPR 0.15%). The no-call rate was 0.5%. In this subgroup, 27.3% (3/11) aneuploidies were diagnosed. The rate of invasive procedures was 2.6%. CONCLUSION: NIPT provides a very high quality for the fetal trisomies 21, 13 and 18 in clinical routine. The results support the recommendation that NIPT should be offered after genetic counseling and only in conjunction with a qualified ultrasound examination.

Expectant management versus multifetal pregnancy reduction in higher order multiple pregnancies containing a monochorionic pair and a review of the literature.

PURPOSE: To compare the perinatal outcome in multifetal pregnancies containing a monochorionic twin pair, managed either expectantly or by fetal reduction (MFPR). METHODS: This was a retrospective analysis of prospectively collected data on 47 triplet and 10 quadruplet pregnancies recruited between 10 and 14 weeks. Main outcome measures were miscarriage <24 weeks, preterm birth, fetal growth restriction, birth weight and survival rates. RESULTS: For triplets the miscarriage rates <24 weeks were 6.3 % after reduction and 20.0 % for expectant management and MFPR, respectively. While we recorded no case of severe preterm delivery <30 weeks in the reduction group, it was 25 % in those with expectant management. Mean gestational age and birth weight were significantly higher after fetal reduction than for the conservative approach (37.7 ± 1.6 weeks vs. 30.9 ± 3.2 weeks, p < 0.01 and 2676 ± 705 g vs. 1429 ± 542 g, p < 0.01). Expectantly managed triplets were complicated by twin-twin transfusion syndrome in 18.8 % and intrauterine fetal death in 8.3 %. Survival rates were 85.4 % for those managed expectantly and 80.0 % after fetal reduction. Mean gestational age of ongoing quadruplets was 26.9 ± 2.0 weeks vs. 34.5 ± 4.3 weeks for those with reduction of the monochorionic pair (p < 0.05). Survival rates were 100 % in the reduction group and 58.3 % in the expectant management group (p < 0.05). There was an inverse correlation between the final number of fetuses and the birth weight. CONCLUSION: Fetal reduction in triplets and quadruplets including a monochorionic pair is associated with decreased early prematurity. While in quadruplets the overall survival is higher after reduction, there was no difference for dichorionic triplets with reduction or conservative management. Complications owing to monochorionicity are frequently observed.

First Trimester Screening - Current Status and Future Prospects After Introduction of Non-invasive Prenatal Testing (NIPT) at a Tertiary Referral Center.

Objective To investigate the uptake of different components of first trimester screening (FTS) and the impact on invasive diagnostic testing (IPT) since the introduction of non-invasive prenatal testing (NIPT) at a level III center. Methods Retrospective data analysis was conducted for singleton pregnancies that presented for FTS between 01/2019-12/2019 (group 1, n = 990). Patients were categorized into three risk groups: low risk for trisomy 21 (< 1 : 1000), intermediate risk (1 : 101-1 : 1000) and high risk (≥ 1 : 100). Uptake of NIPT and IPT was analyzed for each of the risk groups. Results were compared to a previous cohort from 2012/2013 (immediately after the introduction of NIPT, group 2, n = 1178). Results Group 1 showed a significant increase in the use of NIPT as part of FTS (29.5% vs. 3.7% for group 2, p = 0.001) in all three risk groups. Overall IPT rates were lower in group 1 (8.6%) vs. group 2 (11.3%, p = 0.038), mainly due to a significant reduction of IPT in the intermediate risk group. IPT rates in the high-risk group remained stable over time. Conclusion Appropriate clinical implementation of NIPT is still currently a challenge for prenatal medicine experts. Our data suggest that widespread uptake of NIPT is becoming more common these days; however, a contingent approach might prevent redundant uptake.

Brain-Derived Neurotrophic Factor in Gestational Diabetes: Analysis of Maternal Serum and Cord Blood Pairs and Comparison of Dietary- and Insulin-Dependent GDM.

The Objective of our study was to investigate the influence of dietary (dGDM) and insulin-dependent (iGDM) gestational diabetes (GDM) on BDNF blood levels of corresponding maternal-neonatal pairs and compare them to pregnancies unaffected by GDM. Blood samples from 293 maternal-neonatal pairs were analyzed. Statistical analysis was performed using multiple regression analysis for association of log-transformed maternal and neonatal BDNF levels in relation to GDM, gestational age, neonatal sex, and mode of delivery. This was followed by a 2:1 matching of healthy and diabetic pairs. Maternal and neonatal BDNF levels were lowest in the iGDM group, followed by the dGDM group and healthy controls (maternal: healthy 665 ± 562 (26-2343) pg/mL vs. dGDM 593 ± 446 (25-1522) pg/mL vs. iGDM 541 ± 446 (68-2184) pg/mL; neonate: healthy 541 ± 464 (9.5-2802) pg/mL vs. dGDM 375 ± 342 (1-1491) pg/mL vs. iGDM 330 ± 326 (47-1384) pg/mL). After multiple regression analysis and additional 2:1 matching neonatal log-BDNF was significantly lower (-152.05 pg/mL, p = 0.027) in neonates of mothers with GDM compared to healthy pairs; maternal log-BDNF was also lower (-79.6 pg/mL), but did not reach significance. Our study is the first to analyze BDNF in matched maternal-neonatal pairs of GDM patients compared to a metabolically unaffected control group.

Impact of Diet Quality during Pregnancy on Gestational Weight Gain and Selected Adipokines-Results of a German Cross-Sectional Study.

While nutrition during pregnancy is critical for the health of both mother and child, little is known about the diet quality of women during pregnancy, its correlation with gestational weight gain (GWG)/body composition, and chosen maternal adipokines. Therefore, we evaluated the Healthy Eating Index (HEI) of 110 pregnant women and analyzed its correlation with GWG/body composition, physical activity, leptin, resistin, adiponectin, and interleukin 6 (IL-6), respectively. Diet quality was medium in 63% of women, characterized by a high intake of animal-based products. HEI was negatively influenced by pre-pregnancy obesity (ß = −0.335, p = 0.004), and positively influenced by higher age (>35 yrs., ß = 0.365, p ≤ 0.001), upper arm circumference (ß = 0.222, p = 0.052), and total activity during the third trimester (ß = 0.258, p = 0.008). GWG was associated with pre-pregnancy obesity (ß = −0.512, p ≤ 0.001), thigh circumference (ß = 0.342, p = 0.007), upper arm fat area (ß = 0.208, p = 0.092), and maternal age group (>35 yrs. ß = −0.166, p = 0.082), but not with HEI. Leptin and IL-6 displayed associations with variables representative of body composition, such as pre-pregnancy BMI, thigh circumference, upper arm fat area, and upper arm circumference, but were not influenced by HEI. Neither were adiponectin and resistin. IL-6 was also associated with total activity. In conclusion, GWG, leptin, and IL-6 were influenced by nutritional status (body composition/pre-pregnancy BMI), not by maternal diet. Physical activity level also had an impact on IL-6. Thus, efforts should be intensified to improve diet quality and participation in sports before and during pregnancy, particularly in overweight or obese women.

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review.

OBJECTIVE: An increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF). METHODS: In this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay. RESULTS: In 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01). CONCLUSION: Our study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.

Relationship between Physical Activity and the Metabolic, Inflammatory Axis in Pregnant Participants.

Physical activity (PA) during pregnancy is beneficial for mother and child. Little is known regarding the effects of PA on specific adipokines/myokines and their impact during pregnancy. This study investigates the correlation between PA during late pregnancy, body composition, and maternal levels of leptin, IL-6, and TNF-α at delivery. In a cross-sectional study of 91 pregnant participants (mean age 33.9 ± 4.6 years) without gestational diabetes mellitus or preeclampsia, anthropometric data and blood samples were taken at delivery. PA during the third trimester was measured via the Pregnancy Physical Activity Questionnaire. Activities were ranked by intensity: sedentary (<1.5 metabolic equivalent (METs)), light (1.5-3.0 METs), moderate (3.0-6.0 METs), and vigorous activity (>6.0 METs). Leptin at delivery correlated positively with body composition and negatively with light PA intensity. Sedentary behaviour showed a positive correlation with IL-6 levels at delivery. Moderate activity during the last trimester, sedentary activity levels, and body composition had the greatest influence on maternal IL-6 at delivery. Completed weeks of pregnancy, moderate and light PA, and sedentary activity had the greatest influence on maternal TNF-α at delivery. PA during late pregnancy potentially affects circulating (adipo-)/myokines. Further studies are needed to examine causal relationships and the impact on maternal and new-born health.

High Maternal and Low Cord Blood Leptin Are Associated with BMI-SDS Gain in the First Year of Life.

BACKGROUND: Early infant weight development influences metabolic regulation later in life. For the prevention of obesity and metabolic diseases, it is important to understand the underlying mechanisms in detail. OBJECTIVES: This study aims to examine the effects of maternal anthropometric, sociodemographic, and lifestyle factors on maternal and cord blood leptin levels at birth and on the development of body mass index (BMI) standard deviation scores (SDS) in offspring up to 1 year of age. METHODS: Seventy-six mother-child pairs were enrolled in this follow-up analysis in a cross-sectional design. Standardized questionnaires were used to collect information regarding maternal anthropometrics, lifestyle habits, and sociodemographic conditions, and newborn weight, or, rather, BMI-SDS, development during the first year of life. RESULTS: Cord blood leptin (ß = -0.222, p = 0.074), maternal leptin (ß = 0.414, p = 0.001), and female sex of the offspring (ß = 0.385, p = 0.003) explained 29.0% of the variance in BMI-SDS changes in the first year of life. Cord blood leptin was influenced by newborn sex (male; ß = -0.220, p = 0.025) and maternal moderate-intensity physical activity in the third trimester (ß = 0.265, p = 0.007, corr. R2 = 9.2%); maternal leptin was influenced by maternal prepregnancy BMI (ß = 0.602, p < 0.001) and weight gain during pregnancy (ß = 0.247, p = 0.004, corr. R2 = 35.5%). CONCLUSIONS: Higher maternal and lower cord blood leptin levels are associated with a higher BMI-SDS increase during the first year of life. Maternal leptin is influenced by maternal BMI and weight gain during pregnancy, and cord blood leptin is influenced by maternal physical activity; therefore, it can be suggested that an active and healthy maternal lifestyle may play a pivotal and beneficial role in the offspring's weight development.

Adipokine-myokine-hepatokine compartment-system in mothers and children: An explorative study.

OBJECTIVE: Maternal lifestyle during pregnancy has an effect of gestational development and neonatal outcome. Overweight gravidas and gravidas with excessive weight gain have an increased risk of gestational complications and neonatal metabolic disorder. The underlying mechanisms are still under discussion, but the hormonally active fat mass and its biomarkers, adipocytokines, may play a key role by potentially having a direct impact on the metabolic homeostasis of the system in concert with other biomarkers like hepatokines and myokines. Up to now little is known in terms of lifestyle habits and their effect on this complex model on maternal and fetal outcome. Therefore, we aim to investigate the influence of maternal lifestyle clusters during pregnancy on the maternal and fetal biomarkers of compartments, specifically those implying maternal fat and muscle mass, maternal liver and the placenta and who are associated with maternal body composition and birth weight. METHODS: In this exploratory pilot study at least 100 singleton pregnancies and their newborns will be included. The women will undergo assessments of anthropometric measurements, venous blood samples will be drawn and physical activity and nutritional status will be collected through questionnaires. Newborns will undergo assessments of anthropometric measurements, umbilical cord samples will be drawn and birth outcomes will be evaluated. We will measure adipokines, myokines and hepatokines and relate them to maternal lifestyle clusters and fetal outcome. CONCLUSION: Our study will be the first to examine the relationship between maternal body composition, birth weight and potential biomarkers based on an innovative compartment model.

Monochorionic diamniotic in vitro fertilization twins have a decreased incidence of twin-to-twin transfusion syndrome.

OBJECTIVE: To compare the incidence of twin-to-twin transfusion syndrome (TTTS) in spontaneous versus IVF-conceived twin pregnancies. DESIGN: Retrospective multicenter study. SETTING: University-affiliated tertiary medical centers. PATIENT(S): Women admitted for 11-14 week's scan between January 1997 and July 2013 who were diagnosed with monochorionic (MC) diamniotic twin pregnancies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mode of conception, TTTS. RESULT(S): The study cohort included 327 pregnant women with live MC diamniotic twins. Of them, 284 (86.9%) and 43 (13.1%) were spontaneous and IVF conceived, respectively. The mean maternal age was significantly higher in IVF compared with in spontaneously conceived pregnancies (33.8 ± 5.5 vs. 31.6 ± 5.4, respectively). Thirty-seven twins (11.3%) had TTTS, of whom 36/284 (12.7%) versus 1/43 (2.3%) were spontaneously and IVF conceived, respectively. The mean week of delivery was significantly lower in MC twins diagnosed with TTTS compared with those without TTTS (32.7 ± 3.3 vs. 35.5 ± 2.5, respectively). Furthermore, there was a significantly higher birthweight discordancy in twins diagnosed with TTTS compared with those without (20.6% vs. 11%, respectively). CONCLUSION(S): The significantly lower proportion of TTTS found in IVF-conceived twins may suggest a different embryological process that lies at the core of IVF conception of monozygotic twinning.

Progressive cardiac dysfunction in Bethlem myopathy during pregnancy.

BACKGROUND: Bethlem myopathy is a congenital myopathy presenting with muscle weakness and joint abnormalities. Although cardiac involvement is frequent in other inherited myopathies, it has not yet been described in Bethlem myopathy. CASE: We report a case of progressive deterioration of left ventricular function during pregnancy in a patient with Bethlem myopathy. Worsening of clinical symptoms, particularly dyspnea, necessitated delivery at 36 2/7 weeks of gestation. Myocardial function recovered postpartum with improvement of clinical symptoms. CONCLUSION: Bethlem myopathy may be associated with progressive left ventricular dysfunction during pregnancy and may require early delivery.

Antiplatelet effects of antidepressant treatment: a randomized comparison between escitalopram and nortriptyline.

INTRODUCTION: Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation. METHODS: Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting. Depressed patients were randomized to two groups treated either with escitalopram (n=47) or nortriptyline (n=44). Platelet aggregation was studied on days 0, 1, 3, 7, 14, 21, 84 of continuing medication and was determined in response to adenosine diphosphate (ADP) and collagen. RESULTS: Platelet aggregation induced by ADP was increased among depressive patients compared with that of healthy controls (26%, p=0.006). With antidepressant treatment, changes in platelet aggregation remained comparable in both groups at early time points (d1 to 21). In contrast, at day 84, patients with antidepressive response revealed significant differences in both medication groups: Patients receiving escitalopram showed a 23% decrease of ADP induced aggregation (p=0.03) and a 15% decrease of collagen induced aggregation (p=0.03). With nortriptyline the increase in impedance was reduced by 29% after ADP induction (p=0.046). CONCLUSION: Depressed patients have higher ex vivo platelet aggregation that may contribute to increased cardiovascular morbidity. After three months of antidepressant treatment with either escitalopram or nortriptyline, platelet aggregation was significantly reduced in antidepressant responders, irrespective of the antidepressant medication type.