Second systolic peak in fetal middle cerebral artery Doppler after intrauterine transfusion.

OBJECTIVE: To evaluate functional relationship between fetal circulatory response to intrauterine transfusion (IUT) as a circulatory challenge and appearance of second systolic peak (P2) in middle cerebral artery (MCA) based on hemodynamic principles. METHODS: According to the concept of pulse wave (PW) propagation and reflection in adults, PWs arrive twice at cerebral circulation, as primary wave caused by left ventricle ejection and secondary after reflection in peripheral arteries. Thus adults show a biphasic contour of systolic blood flow in cerebral arteries. Similar waveforms may appear in fetal MCA-Doppler, as a response to IUT as a circulatory challenge. This is a proof-of-principle study, applying classical hemodynamic principles to fetal circulation. Accordingly, appearance of MCA-P2 may indicate vasoconstriction with increased PW reflection and timing of P2(Δt) should agree with the additional PW travel time down to reflection and return (Tr). To test this agreement, we searched our database for IUTs performed for severe fetal anemia, and compared Δt, obtained by Doppler, with Tr, obtained by hemodynamic calculation using human fetal data. Level of agreement was assessed using Bland-Altman-Plots. RESULTS: We identified 21 fetuses with adequate Doppler quality for Δt evaluation. In four cases (19%) MCA-P2 was observed before the intervention, and in 17 interventions (81%) thereafter; a highly significant association between IUT and P2 appearance (p < 0.001). In these 17 interventions good agreement of P2 timing was found between Doppler assessment: Δt = 80 ± 8 ms, and hemodynamic calculation: Tr = 76 ± 4 ms. CONCLUSION: P2 appearance in fetal MCA-Doppler seems to indicate PW reflection due to increased vasoconstriction after IUT. Thus hemodynamic considerations might enable Doppler monitoring of fetal vasoconstriction.

M-Sign in Middle Cerebral Artery Doppler Waveforms: A Sign of Fetal Vasoconstriction Before and After Open Fetal Spina Bifida Repair.

BACKGROUND: Increased pulse wave reflection in the fetal arterial system, illustrated by a second systolic peak (M-sign) in middle cerebral artery (MCA) Doppler waveforms, allows interpretation of fetal systemic vasoconstriction. Little is known about fetal vascular regulation during fetal spina bifida (fSB) repair. Therefore, the aim of this study was to analyze MCA-Doppler waveform changes before, during, and after fSB repair. PATIENTS AND METHODS: 31 pregnant women who underwent fSB repair were included. Fetal MCA-Doppler waveforms were prospectively analyzed before, during and after fSB repair, and categorized as follows: normal systolic downslope, systolic shoulder, second systolic peak (M-sign), and concave systolic downslope. These MCA waveforms were related to maternal and fetal characteristics, to anesthetic medication, and to umbilical artery (UA) waveforms. RESULTS: Before fSB repair, all fetuses repeatedly presented M-signs. After initiation of desflurane for general anesthesia, systolic shoulder and the M-sign vanished in 24/31 (78%) fetuses and 19/31 (61%) showed transient UA ARED flow. A significant association between these two Doppler findings was found (p=0.007). After fSB repair, signs of increased pulse wave reflection reappeared but resolved over time (23 days ± 20, SD) in all fetuses. CONCLUSION: Both fSB and intrauterine repair influence fetal vascular regulation. This phenomenon can be illustrated by MCA-Doppler waveforms. While anesthetic agents transiently eliminated M-signs and often provoked a UA ARED flow, fSB repair finally led to normalization of MCA-Doppler waveforms indicating return to normal fetal vascular regulation.

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures. / Empfehlungen der DEGUM, der ÖGUM, der SGUM und der FMF Deutschland zum Einsatz von Ersttrimester-Screening, früher Fehlbildungsdiagnostik, Screening an zellfreier DNA (NIPT) und diagnostischen Punktionen.

First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values.

Prenatal diagnosis of abnormally invasive placenta reduces maternal peripartum hemorrhage and morbidity.

OBJECTIVE: Abnormally invasive placenta (AIP) poses diagnostic and therapeutic challenges. We analyzed clinical cases with confirmed placenta increta or percreta. DESIGN: Retrospective case series. SETTING: Multicenter study. POPULATION: Pregnant women with AIP. METHODS: Chart review. MAIN OUTCOME MEASURES: Prenatal detection rates, treatment choices, morbidity, mortality and short-term outcome. RESULTS: Sixty-six cases were analyzed. All women and all but three fetuses survived; 57/64 women (89%) had previous uterine surgery. In 26 women (39%) the diagnosis was not known before delivery (Group 1), in the remaining 40 (61%) diagnosis had been made between 14 and 37 weeks of gestation (Group 2). Placenta previa was present in 36 women (54%). In Groups 1 and 2, 50% (13/26) and 62% (25/40) of the women required hysterectomy, respectively. In Group 1 (unknown at the time of delivery) 69% (9/13) required (emergency) hysterectomy for severe hemorrhage in the immediate peripartum period compared with only 12% (3/25) in Group 2 (p = 0.0004). Mass transfusions were more frequently required in Group 1 (46%, 12/26 vs. 20%, 8/40; p = 0.025). In 18/40 women (45%) from Group 2 the placenta was intentionally left in situ; secondary hysterectomies and infections were equally frequent (18%) among these differently treated women. Overall, postpartum infections occurred in 11% and 20% of women in Groups 1 and 2, respectively. CONCLUSIONS: AIP was known before delivery in more than half of the cases. Unknown AIP led to significantly more emergency hysterectomies and mass transfusions during or immediately after delivery. Prenatal diagnosis of AIP reduces morbidity. Future studies should also address the selection criteria for cases appropriate for leaving the placenta in situ.

Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis.

AIMS: The aim of this study was to investigate the current prenatal "off-label use" of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. METHODS: This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12-36 months after birth. RESULTS: Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero, at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero. In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. CONCLUSION: CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG.

Prolonged preterm rupture of fetal membranes, a consequence of an increased maternal anti-fetal T cell responsiveness.

A fetus, although semi-allogeneic, is usually accepted by the maternal immune system. However, complications, including alloresponsive mechanisms, are thought to be potentially detrimental for a successful pregnancy. Therefore, we compared allogeneic T cell responses of nonpregnant women with the response of healthy pregnant women and pregnant women who have various gestation-associated diseases. Peripheral blood mononuclear cells (PBMCs) of all three groups were stimulated with PBMCs from unrelated volunteers. Pregnant women had significantly reduced stimulation indices (SIs) compared with nonpregnant women. Exposing PBMCs from pregnant women to PBMCs of their own fetus led to a further significant decrease of SIs. Among the two groups of pregnant individuals, SIs of women with prolonged preterm rupture of fetal membranes (PPROM) were significantly higher when the maternal PBMCs were stimulated with PBMCs of their own fetus. This phenomenon could not be observed after stimulation with PBMCs from unrelated volunteers. In addition, an increased humoral immune response was assessed for women with PPROM in comparison with women with uncontrollable preterm labor. Our results revealed a strongly reduced allogeneic T cell response of PBMCs from pregnant women that was further down-regulated when PBMCs from their own fetus were used as stimulators. By contrast, data from women with PPROM suggest an increased maternal T cell response specifically toward the fetal HLA antigens.