Background Galectins (gal) are glycan-binding proteins that regulate maternal adaptations during pregnancy, but their role in pregnancy-associated metabolic homeostasis is unclear. This study characterizes the maternal galectin profile in response to an oral glucose tolerance test (OGTT) in pregnant women with varying body weight. Methods In a two-center prospective study, pregnant women were recruited into two cohorts: low-risk (LR) with normal weight and high-risk (HR) with overweight or obesity. Circulating levels of gal-1, -3, -7, and -9 were measured at fasting, 1 hour, and 2 hours during the OGTT between 24 and 28 weeks of gestation. Correlations with clinical and metabolic parameters were assessed (HMO study: ClinicalTrials.gov Identifier NCT05496712; FitFor2 trial: trial registration number NTR1139). Results Fasting gal-3 and gal-9 were elevated in the HR cohort compared to the LR cohort. Body mass index was positively associated with gal-3 and gal-9, while gal-3 was also linked to insulin sensitivity. After glucose challenge, gal-1, -3, -7, and -9 decreased in the LR cohort; in the HR cohort, only gal-1 and gal-7 decreased after 2 hours, while gal-3 and gal-9 remained unchanged. Gal-1 correlated positively with homeostasis model assessment for insulin resistance (HOMA-IR) and inversely with insulin sensitivity across the OGTT in the LR cohort, but some of these correlations were not observed in the HR cohort. Conclusion Galectins exhibited distinct patterns of association with glucose homeostasis during the second trimester of pregnancy. Gal-3 and gal-9 are associated with chronic conditions such as pre-pregnancy obesity and insulin resistance, whereas gal-1 appears to be particularly sensitive to the acute glucose challenge.
(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24–28 gestational weeks was analyzed for HMOs (2′FL, 3′SLN, LDFT, 3′SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3′SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3′SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3′SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.
Introduction: This work explores the feasibility of simultaneous and continuous intra-abdominal, intra-uterine, and arterial blood pressure measurements to examine the hemodynamic perturbation expected during therapeutic amnioreduction and to better understand the protective role of the placenta during that treatment. Methods: Patients with twin -to -twin transfusion syndrome were treated with fetoscopic laser ablation followed by amnioreduction. Intra-abdominal, intra-uterine, and mean arterial pressures were simultaneously recorded during amnioreduction performed in steps of 200 mL. Placental thickness and uterine dimensions were measured before and after amnioreduction by ultrasonography. Results: Useful pressure recordings were obtained between volume reduction steps and short hands-off periods in four studies. Median amnioreduction volume was 1400 mL corresponding to a median uterine volume reduction of 1121 mL. Mean intra-uterine pressure significantly fell from 24.8 to 13.6 mmHg ( p = 0.011) and intraabdominal pressure significantly decreased from 13.4 to 9.2 mmHg after amnioreduction ( p = 0.015). Uterine pressure recordings revealed transient contractions ( A , in mmHg) following individual amnioreduction steps, which increased with fractional amnioreduction ( F , no dimension) ( A = 17.23* F + 11.81; r = 0.50, p = 0.001). Discussion: Simultaneous and continuous measurement of intra-abdominal, intra-uterine, and arterial blood pressures during amnioreduction is feasible. The dynamics reveal transient uterine contractions reaching levels comparable to those seen during childbirth which seem to oppose impending maternal hypovolemia by placental steal at the expense of temporarily reducing placental perfusion pressure and underline the importance of uterine and placental interaction.
Pregnancy poses a challenge to the maternal metabolism and suboptimal adaptations can predispose individuals to metabolic and cardiovascular diseases in the future. Galectins are multifunctional regulators in pregnancy and may play roles in cardiovascular diseases and metabolic disorders. In this study we investigated serum galectins (gal-1, gal-3, gal-9) in a well characterized healthy pregnancy cohort during an oral glucose test (OGTT) and assessed their associations with metabolic markers (including insulin sensitivity, insulin secretion). Galectins were measured by ELISA in maternal serum at 0 h, 1 h, 2 h post glucose load (75 g) during an OGTT at 24-28 gestational weeks in a healthy pregnancy cohort. Glucose, insulin and c-peptide were used to calculate insulin sensitivity/secretion indices. Our results showed that gal-1, gal-3 and gal-9 were significantly reduced from 0 h to 2 h post glucose load. Higher serum gal-1 at 0 h, 1 h, 2 h was associated with lower insulin sensitivity (Matsuda index) and higher insulin resistance (HOMA-IR). Changes of serum galectins during an OGTT and the associations of gal-1 with glucose metabolism suggest that galectins play a role in regulating metabolic adpations during healthy pregnancy.
Zielsetzung Vergleich des sonographisch gemessenen präpartalen Geburtsgewichts mit dem tatsächlichen Geburtsgewicht bei Kindern mit und ohne Schulterdystokie.
Einleitung: In 1 – 2% aller Konzeptionen tritt eine Triploidie auf. Hierbei ist ein zusätzlicher haploider Chromosomensatz von maternaler (digynisch) oder von paternaler Seite (diandrisch) vorhanden. Somit bestehen 3 möglichen Karyotypen: 69, XXX, 69, XXY, und kaum vorkommend 69, XYY. Im Schwangerschaftsverlauf kommt es zu einer drastischen Abnahme der Prävalenz einer Triploidie. Diese stellt in Verbindung mit einem lebenden Fetus im zweiten Trimenon eine Rarität (1 : 250 000) dar. Triploide Feten weisen oftmals multiple strukturelle Fehlbildungen ohne spezifisches Muster auf.
Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 ± 8.1 mmHg to 17.6 ± 3.6 mmHg (p < 0.001)) and an increase in mean placental thickness (from 16.8 ± 6.4 mm to 31.83 ± 8.64 mm (p < 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson’s Rho 0.73; p = 0.001). Hematocrit decreased from 33.4 ± 3.8 (%) to 28.4 ± 3.5 (%), i.e., an increase in relative blood volume by 18 ± 10.2 % (p < 0.001). Albumin decreased from 37.9 ± 0.9 g/L to 30.7 ± 2.2 g/L, i.e., an increase in relative plasma volume by 24 ± 8.1% (p < 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term “amniodrainage-induced circulatory dysfunction” for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome.
Triploidy occurs in 1-2% of human conceptions and is caused by an additional haploid chromosome set from either maternal (digynic) or paternal (diandric) origin. There are three possible karyotypes: 69,XXX, 69,XXY, and rarely 69,XYY. The vast majority of triploidies results in early pregnancy failure and survival beyond the second trimester is rare. Affected fetuses typically present with structural anomalies and growth restriction. A 33-year-old woman (G2/P1) presented at 20+2 weeks of gestation with suspected fetal ventriculomegaly and multicystic kidneys. Expert ultrasound examination confirmed ventriculomegaly and additionally detected micro-lissencephaly, unilateral multicystic kidney disease, ventricular septal defect and a small omphalocele. The placenta appeared significantly enlarged with multiple large lacunae and a thickness of > 70mm. Fetal triploidy was suspected mainly due to placental features. Amniocentesis was performed confirming the karyotype 69,XXY. A fetocide was performed on parents' request and subsequently stillbirth was induced, and curettage was conducted. Placental investigation confirmed the presence of partial mole and the patient had follow-up examinations until beta-HCG levels were negative. The evaluation of placental morphology is of diagnostic value during second trimester ultrasound for differentiation of triploidy from other genetic anomalies like Trisomy 13 and 18. Supporting information can be found in the online version of this abstract Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Methods: This was a retrospective study including 45 fetuses diagnosed of MCD from January 2000 to January 2020. We reviewed standardised axial planes obtained by transabdominal US and we evaluated cortical grading of Sylvian fissure (as well as its abnormal morphology), pareto-occipital (P-O) sulcus and cortical regions (parietal, temporal and frontal) as described by Pistorius et al. We also evaluated indirect signs as atrium width, suspected anterior horns dilation, enlargement of subarachnoid space, and head circumpherence (HC). To confirm the diagnosis of MCD prenatal magnetic resonance or postmortem histological findings were used. Results: Median gestational age at evaluation was 28 weeks (20–37 weeks). Associated anomalies were identified in 46.6% (21/45) of cases, 8 extracranial malformations and 13 other intracranial malformations such as corpus callosum or cerebellum alterations. In 91% (41/45) Sylvian fissure grading was delayed or its morphology was clearly altered. Of the 4 cases with normal Sylvian fissure, 2 cases had delayed P-O sulcus due to MCD focused on parieto-occipital region, one case was a megaencephlay at 22 weeks of pregnancy and one fetus had focal dysplasia in frontal region. The P-O sulcus and cortical regions weredelayed in 73% (n = 33) and 60% (n = 27) of cases. Among indirect signs, HC was altered in 14 cases (9 microcephaly and 5 macrocephaly), anterior horns were dilated in 25% of the fetuses, and ventriculomegaly was present in 20% of the cases. Conclusions: Our results demonstrated that Sylvian fissure grading and morphology is altered in almost all cases of MCD and could be identified during transabdominal routine scan. These results reinforce the utility of evaluating Sylvian fissure in routine ultrasound to increase the diagnosis of MDC.
Ultrasound in Obstetrics & GynecologyVolume 56, Issue S1 p. 57-57 AbstractFree Access VP01.01: Abstract withdrawn First published: 15 October 2020 https://doi.org/10.1002/uog.22345AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Supporting Information Filename Description uog22345-sup-0001-supinfo.jpgWord 2007 document , 538 KB Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume56, IssueS1October 2020Pages 57-57 RelatedInformation
Objectives: To evalute fetal MRI referred for evaluation of isolated ventriculomegaly for presence of sulcal asymmetry and to evaluate effect of sulcal asymetry on pregnancy survival and develpmental outcomes. Methods: This retrospective cohort study was done from September 2013 to 2016 out of the 658 fetal MRI’s performed in our tertiary care referral hospital finally 67 fetuses with isolated ventricolomegalia and 77 fetuses with normal fetal brain MRI include into our study. MRI images had review by two expert radiologist in fetal-MRI separately in blinded mode. Final outcomes and mental developing had measured by ASQ questionnaires obtained at least one year post-delivery. Finally, all data analysis duo to not normally distribution, correlation coefficient with ANCOVA and Spearman’s. intraclass correlation coefficient calculated and Bland-Altman plots on SPSS. Results: Fetuses with isolated ventricolomegalia had significant delayed sulcation when compared to controls specially regarding the calcarine sulcus and parieto-occipital fissures. In addition, secondary sulcus development shows significant delayed correlated with gestational age. Neonates with prenatally diagnosed isolated ventricolomegalia had decreased ASQ score in comparison with normal group. At year 2 of age, only 39% of the children assessed had a normal neurodevelopment also 8% neonatal death was detected in the isolated ventricolomegalia groups. Conclusions: Isolated ventricolomegalia is a poor prognostic factor in the fetus in the survival and also development. Fetuses with ventriculomegaly and sulcal asymmetry/delay had a poorer prognosis regarding survival and postdelivery neurodevelopment.
Das feto-fetale Transfusionssyndrom (FFTS) ist eine häufige Komplikation monochorialer Zwillingsschwangerschaften. Unbalanzierte Blutflüsse im Bereich plazentarer Anastomosen führen zu typischen Veränderungen der Volumenumverteilung zwischen den Feten bis hin zum intrauterinen Absterben. Die einzig kausale Therapie stellt die intrauterine Laserkoagulation der Gefäßanastomosen dar. Im Anschluss daran wird regelmäßig eine Amniodrainage durchgeführt. Hierbei konnte bereits gezeigt werden, dass es zu Veränderungen der maternalen Hämodynamik und zur Hämodilution kommt. Die ursächlichen Mechanismen sind gänzlich ungeklärt. Wir untersuchten die Dekompression des uterinen Kompartiments während Amniodrainage mit konsekutiven Plazentaveränderungen.
Background: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia. Objective: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF. Methods: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum). Results: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia. Conclusions: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.
Twin-to-twin transfusion syndrome (TTTS) is a challenging complication in monochorionic diamniotic (MCDA) twins. Intrauterine interventions, such as fetoscopic laser ablation and cord occlusion followed by amniodrainage, are established treatments. Little is known about maternal complications and hemodynamics following these interventions. We performed a retrospective analysis of maternal procedure-related complications and the impact of such procedures on maternal hemodynamics and blood characteristics. Within the study period, 100 women with severe TTTS treated by fetoscopic laser ablation (FLA) or cord occlusion (CO) were identified. Clinically relevant maternal complications were reported in four (4%) cases. There was a significant decrease in hemoglobin, hematocrit, and albumin between admission and postoperative measurements (all p < 0.001). Systolic and diastolic blood pressure, as well as maternal heart rate, decreased from time of skin suture to postoperative measurements (all p < 0.001). Within a 24 h interval, there was a positive correlation between hematocrit (Spearman's rho 0.325; p = 0.003), hemoglobin (Spearman's rho 0.379; p < 0.001), and albumin (Spearman's rho 0.360; p = 0.027), and the amount of amniodrainage during the intervention. Maternal procedure-related complications are relatively rare. Significant hemodynamic alterations and maternal hemodilution are common clinical findings following intrauterine interventions.
Human milk oligosaccharides (HMOs) are present in maternal serum in early gestation, raising the question of whether HMOs can cross the placental barrier and reach fetal circulation. Here, we aimed to detect HMOs in cord blood, and assess HMO composition and concentration in relation to maternal HMOs. In an ex-vivo placental perfusion model, we asked whether HMOs can pass over the placenta. Using HPLC, we measured HMOs in maternal serum and matching venous cord blood samples collected at delivery from normal pregnancies (n = 22). To investigate maternal-to-fetal transport, we perfused isolated placental cotyledons from term pregnancies (n = 3) with 2’-fucosyllactose (2′FL) in a double closed setting. We found up to 18 oligosaccharides typically present in maternal serum in all cord serum samples investigated. Median total cord blood HMO concentration did not differ from the concentration in maternal serum. HMO composition resembled the composition in maternal serum, with the strongest correlations for 2′FL and LDFT. After 180 min perfusion, we found 22% of maternally offered 2′FL in the fetal circuit without reaching equilibrium. Our results provide direct evidence of HMOs in cord blood, and suggest that the placenta transfers HMOs from the maternal to fetal circuit. Future studies will investigate potential differences in the transfer of specific HMOs, or in pregnancy disorders.
Twin–twin transfusion syndrome (TTTS) in monochorionic twin pregnancies often requires intrauterine interventions including fetoscopic laser ablation (FLA) and cord occlusion (CO) followed by amniodrainage. Mirror Syndrome, also referred to as Ballantyne's Syndrome, is reported to occur in cases of fetal or placental hydrops, Hereby, fetal or placental fluid accumulation is “mirrored” by the mother leading to anaemia, haemodilution, hypoproteinaemia, albuminuria and oliguria. Mirror Syndrome has also been reported in the context of TTTS. We conducted a retrospective single centre analysis in 101 cases of TTTS treated with FLA or CO followed by amniodrainage at the Medical University of Graz, Austria, between 08/2010 and 03/2018. Clinically relevant perioperative maternal complications were found in five cases (4.95%). There were four cases (3.96%) of Mirror Syndrome and only one case of retroplacental haematoma (0.99%). Cases of Mirror Syndrome associated with prior intrauterine intervention were diagnosed between 19+6 and 26+1 gestational weeks. Clinical findings were severe anaemia (4/4), hypoproteinaemia (4/4), fluid accumulation (4/4), oliguria (2/4), lung edema (3/4), cardiac decompensation (3/4) and a drop of haemoglobin without clinical signs of haemorrhage (4/4). Fetal outcome was poor with only one survivor after CO and no surviving fetus after FLA (1/8). Surgical complications following intrauterine surgery for TTTS are rare. However, postoperative haemodynamic changes consistent with Mirror Syndrome may be observed in about 4% of cases. Clinicians should be aware of this specific complication which otherwise may be misdiagnosed as acute maternal haemorrhage. The most important treatment option is administration of diuretics while fluid substitution or blood transfusion could deteriorate the condition and should therefore be avoided. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.