Risk factors for fetomaternal bleeding after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To quantify and assess potential risk factors for transplacental passage of fetal red blood cells (RBCs) into the maternal circulation (fetomaternal bleeding, FMB) after laser surgery for twin-twin transfusion syndrome (TTTS). STUDY DESIGN: A retrospective study of Rhesus-D negative patients that underwent laser surgery for TTTS. Patients with and without postoperative detectable fetal RBCs on Kleihauer-Betke (KB) testing were compared to determine risk factors for FMB. Patients were further sub-classified into those with a FMB < 20% and ≥20% of estimated fetoplacental blood volume. RESULTS: Of 60 studied patients, 26/60 (43%) had a positive postoperative KB test. The median fetal:adult RBC ratio was 0.00125, estimated to be a FMB volume of 6.25 mL. There were 17/26 (65%) of patients with FMB < 20% and 9/26 (35%) patients with ≥20% of the fetoplacental blood volume. Stage III-Recipient and III-Recipient/Donor patients were more likely to have a positive KB test (14/21 [66.7%] vs 12/39 [30.8%], OR = 4.50 [1.27-16.54], P = 0.0162). No other risk factors for FMB were apparent. CONCLUSIONS: Fetomaternal bleed appears to be a common finding after laser surgery for TTTS. TTTS Stage, particularly stage III-Recipient and III-Recipient/Donor, appears to be a risk factor for FMB.

[Trauma and pregnancy: Is the Kleihauer-Betke test really useful?] / Traumatisme et grossesse : le test de Kleihauer est-il vraiment utile ?

OBJECTIVE: To evaluate the pertinence of Kleihauer-Betke (KB) test, in case of abdominal trauma during pregnancy in forecast of fetal outcomes, according to trauma severity. METHODS: A single-center retrospective study conducted between January 2014 and April 2016 in a maternity type III and a trauma center, which included the pregnant women admitted for abdominal trauma. The trauma's severity was assessed using the guidelines of the Society of Obstetricians and Gynaecologists of Canada. The impact of a positive KB test, defined as>0.1%, was analyzed. Adverse outcome was defined as one or more of the following complications: intrauterine fetal death, placental abruption, pre-term birth<37 weeks of gestation, and fetal or neonatal anemia. RESULTS: During the study period, 265 pregnancies involved into an abdominal trauma were included: 69% with a minor trauma and 31% with a severe trauma. Of all patients, 5.6% presented a positive KB test, among then 15.4% had an adverse outcome. There was no significant difference in the rate of adverse outcomes in the positive KB group and the KB negative group either in the overall population (P=0.16), in the minor trauma population (P=1) or in the major trauma population (P=0.14). The predictive positive values were respectively in the global population, in the minor trauma group and in the severe trauma group 15.4%, 0% and 25%. CONCLUSIONS: The KB test does not seem to be useful in case of trauma during pregnancy to define adverse outcome.

Biochemical analysis of intraplacental choriocarcinoma and fetomaternal transfusion.

Intraplacental choriocarcinoma is one of the rarest forms of gestational tumors and is believed to be one of the causes of fetomaternal transfusion (FMT). A 35-year-old woman, gravida 2, para 2, with a history of two vaginal deliveries, was incidentally diagnosed as having stage I gestational intraplacental choriocarcinoma with a FIGO/World Health Organization 2000 risk score of 2 after term delivery. This disease caused neonatal anemia but did not metastasize to either the mother or infant. Short tandem repeat analysis with laser microdissection revealed that the tumor had originated from the current pregnancy. Serological test and immunohistochemical analysis revealed that the patient and her baby suffered from FMT. She has been free from disease without any medical intervention for the last 1 year. A combination of multiple biochemical analyses might help us diagnose the precursor pregnancy of a gestational choriocarcinoma and FMT.

Fetomaternal hemorrhage complicated pregnancy: risks, identification, and management.

PURPOSE OF REVIEW: This article aims not only to review recent literature about the clinical features of massive fetomaternal hemorrhage (FMH) and identification of risk factors, but also to alert obstetricians and pediatricians to this underdiagnosed and underestimated severe obstetrical issue. In addition, a simplified flow chart for the antenatal management of suspected FMH is proposed. RECENT FINDINGS: Improvements in obstetrical and neonatal care have decreased perinatal morbidity and mortality and the rate of stillbirth. Unfortunately, because of the nonspecific signs on presentation, adverse outcome associated with massive FMH has not followed this trend and still has devastating consequences. As even the definition varies among publications and there is lack of universal screening, the real nature still remains obscure. Improvements in the diagnosis of fetal anemia, laboratory and intrauterine transfusion techniques, and the implementation of prenatal and postnatal neuroprotection give some hope for the better outcome in the most severe cases. Unfortunately, obstetricians' awareness of the massive FMH remains still at an unacceptably low level. SUMMARY: There is an urgent need for the internationally accepted definition, standardized pregnancy management protocol, and structured follow-up of neonates from such pregnancies. We suggest the international registry of massive FMH cases.

[Fetomaternal transfusion and diagnosis of gestational choriocarcinoma]. / Transfusion materno-fœtale et diagnostic de choriocarcinome gestationnel.

Choriocarcinoma is a rare but agressive malignant trophoblastic neoplasm. Fetomaternal transfusion can be the first sign of choriocarcinoma. We describe two cases of gestational choriocarinoma whose first manifestation was a fetomaternal transfusion. Fetomaternal transfusion is a rare demonstration of choriocarcinoma but its diagnosis must lead to a placenta examination with specific research of choriocarcinoma. The more the therapeutic care is precise, the better is the forecast.

A correlation between severe haemolytic disease of the fetus and newborn and maternal ABO blood group.

OBJECTIVE: To analyse anti-D quantification levels and frequency of intrauterine transfusion (IUT), per maternal ABO blood group. BACKGROUND: Maternally derived red cell allo-antibodies can target fetal red cell antigens in utero leading to haemolytic disease and fetal anaemia. When a clinically significant allo-antibody is formed the priority is ascertaining the risk to the fetus and maternal ABO blood groups are not considered relevant. MATERIALS AND METHODS: This was a 10-year retrospective, observational study carried out on women referred for anti-D quantification (n = 1106), and women whose fetuses required an IUT to treat fetal anaemia (n = 62) due to anti-D, in the Republic of Ireland. RESULTS: Relative to the overall incidence of RhD allo-immunisation by blood group, women of blood group A were more likely to require IUT compared with those who were blood group O (P = 0.002). CONCLUSION: It is known that ABO feto-maternal compatibility can influence the incidence and level of red cell allo-antibodies in pregnancy; however, it does not account for the significantly high rate of severe haemolytic disease requiring IUT seen in blood group A women.

Evaluation of passage of fetal erythrocytes into maternal circulation after invasive obstetric procedures.

AIM: The aim of this study was to evaluate the passage of fetal erythrocytes into the maternal circulation after invasive obstetric procedures, using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration in maternal blood. MATERIAL AND METHODS: This was a prospective descriptive study on patients who underwent: amniocentesis, cordocentesis, chorionic villus sample, amniotic infusion, bladder drainage and ventricular-amniotic shunt to investigate the karyotype; treatment for hydrocephalus, oligohydramnios, obstructive uropathy and polyhydramnios; and investigation of lung maturity. Maternal blood samples were collected before and 60 min after the invasive obstetric procedure in order to evaluate the passage of fetal erythrocytes using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration. RESULTS: In total, 43 invasive obstetric procedures were performed. The procedures performed were: 27 cases of amniocentesis (62.7%), seven cases of cordocentesis (16.2%), four chorionic villus samples (9.4%), two amniotic infusions (4.7%), two ventricular-amniotic shunts and one bladder drainage (2.3%). After one case of cordocentesis with two puncture attempts via the placenta, a significant increase in fetal erythrocytes was detected using the three methods. After another cordocentesis with one puncture via the placenta, a significant increase in fetal erythrocytes was detected using flow cytometry and α-fetoprotein concentration, but not through the Kleihauer-Betke test. The other 41 samples did not show any significant increase in fetal erythrocytes in the maternal blood. CONCLUSION: Invasive obstetric procedures performed during prenatal care are safe when performed by experienced professionals with the proper technique, with minimal chance of passage of fetal erythrocytes into the maternal compartment.

Cell-free fetal DNA in maternal circulation after chorionic villous sampling.

OBJECTIVE: This study aims to estimate whether chorionic villous sampling (CVS) causes a significant increase of cell-free fetal DNA (cffDNA) in maternal circulation. METHOD: Fifty pregnant women with singleton pregnancy were recruited prior to CVS. Maternal peripheral blood was collected before and after CVS. A methylation-sensitive restriction enzyme digestion was used to select the placental-derived hypermethylated promoter of the RASSF1A gene in maternal plasma, thus differentiating cffDNA from mother's cell-free DNA (cfDNA), where the RASSF1A gene is normally hypomethylated. Total cfDNA and cffDNA amounts were compared before and after CVS in each patient. Data were compared using the Student t-test. RESULTS: No significant difference before and after CVS was found between the following: (i) total cfDNA concentration in plasma (p = 0.695); (ii) cffDNA concentration in plasma (p = 0.612); and (iii) percentage of fetal DNA in plasma (p = 0.835). After dividing the cases on the basis of the sex of the fetus, maternal age, gestational age, number of pregnancies, position of the placenta, and presence of trisomy of the fetus, no difference in fetal and total DNA concentrations before and after CVS was observed. CONCLUSION: The CVS does not seem to significantly disrupt the maternal-placental interface, as no significant increase of cffDNA in maternal plasma following CVS was observed.

Massive idiopathic feto-maternal transfusion associated with dilatation of umbilical vein: case report and review of literature.

Feto-maternal transfusion (FMT) or haemorrhage occurs when there is an entry of fetal blood into the maternal circulation in pregnancy or during delivery. It has been stated that very small amount of fetal red cells are normally detectable in maternal circulation in all pregnancies. However, massive FMT is rare and even rarer is the resultant severe anaemia which may cause severe fetal morbidity or early neonatal death in apparently uneventful normal pregnancy. Massive FMT is regarded as a pathological condition with a variety of clinical presentations essentially secondary to the fetal anaemia. We present a case of FMT associated with umbilical vein dilation and speculate whether this finding is of prognostic value.

Fetomaternal hemorrhage with intraplacental chorioangioma.

A 37-year-old Asian woman, gravid 0 para 0, was admitted to our hospital at 34 weeks and 5 days of her pregnancy for management of preeclampsia. A few days after admission, she recognized diminished fetal movement, and a non-stress test revealed a non-reassuring fetal heart rate pattern with decreased variability. A female baby weighing 1840 g was delivered by emergency cesarean section with Apgar scores of 5 and 5 at 1 and 5 min, respectively. Significant neonatal anemia with a hemoglobin level of 4.3 g/dL was observed. The elevated level of hemoglobin F (HbF) in the maternal blood accounted for 4.6% (normal≦0.5%), and was indicative of the presence of fetomaternal hemorrhage (FMH). Microscopic examination of the placenta revealed chorioangioma. We report here a rare case of FMH with intraplacental chorioangioma, and discuss the relationship between these two pathologies.

Assessment of fetomaternal hemorrhage by Kleihauer-Betke test, flow cytometry and α-fetoprotein after invasive obstetric procedures.

PURPOSE: The aim of this study was to evaluate the passage of fetal red blood cells to the maternal circulation, after invasive obstetric procedures, through the Kleihauer-Betke test, flow cytometry and by measurement of maternal serum alpha-fetoprotein level. METHODS: This prospective descriptive study with patients submitted to amniocentesis, cordocentesis, chorionic villus sampling (CVS), amnioreduction and ventriculoamniotic shunt was performed for karyotype analysis, treatment of hydrocephalus and polyhydramnios and to assess fetal lung maturity. Maternal blood samples were collected before and 60 minutes after the invasive obstetric procedure to search for fetal erythrocytes using the Kleihauer-Betke test, flow cytometry and serum alpha-fetoprotein measurement. RESULTS: Ten invasive obstetric procedures were performed. The mean age of the patients was 29.2 years and the mean gestational age was 29.6 weeks. The procedures were: five amniocenteses, two cordocenteses, one CVS, one ventriculo-amniotic shunt and one amnioreduction with cephalocentesis. The indications for the procedures were: karyotype analysis in five patients, fetal lung maturity assessment in two patients, amnioreduction in one patient, fetal hydrocephalus shunt in one patient and polyhydramnios related to hydranencephaly in one patient. Regarding the path of puncture, three procedures were accomplished through the placenta and seven apart from it. All punctures were successful at the first attempt. There was no significant increase of fetal erythrocyte quantity in maternal blood samples using the Kleihauer-Betke test. After cordocentesis, a significant increase of fetal erythrocytes was detected by flow cytometry and serum alpha-fetoprotein measurement. CONCLUSION: Invasive obstetric procedures during prenatal care are safe when performed by experienced professionals using adequate techniques, with minimal chance of passage of fetal erythrocytes from the fetal compartment.

[The influence of maternal age, parity, gestational age and birth weight on fetomaternal haemorrhage during spontaneous delivery]. / Vliv veku rodicky, parity, délky trvání tehotenství a hmotnosti plodu na fetomaternální hemoragii pri spontánním porodu.

OBJECTIVE: Determine the influence of maternal age, parity, gestational age and birth weight on the volume of fetal erythrocytes which enter the maternal circulation during spontaneous delivery. Determining these parameters would enable improving the guidelines for RhD alloimmunization prophylaxis. DESIGN: Prospective clinical study. SETTING: Department of Obstetrics and Gynecology, University Hospital, Olomouc. METHODS: A total of 2413 examinations were performed. The amount of fetal erythrocytes entering maternal circulation during uncomplicated spontaneous delivery of one fetus was determined by flow cytometry using the BDFACSCanto cytometer (Becton Dickonson International). Laboratory processing: Fetal Cell Count kit (Diagnosis of Feto-maternal transfusion by flow cytometry), IQ Products, IQP-379. Calculation of total volume of fetal erythrocytes entering maternal circulation: Scientific Subcommittee of the Australian and New Zealand Society of Blood Transfusion. Guidelines for laboratory assessment of fetomaternal haemorrhage. 1st ed. Sydney: ANZSBT, 2002: 3-12. RESULTS: The average maternal age when FMH 1.8 ml (95 perc) was 29.4 years vs. 29.1 years when FMH > 1.8 ml, median 30 years in both groups, the difference was not statistically significant (p = 0.501). The average gestational age when FMH 1.8 ml (95 perc) was 275.3 days vs. 276.9 days when FMH > 1.8 ml, median 278 days (39 weeks +5 days) vs. 276 days (39 weeks + 3 days), the difference was not statistically significant (p = 0.849). The average birth weight when FMH 1.8 ml (95 perc) was 3312 g vs. 3353 g when FMH > 1.8 ml, median 3340 g vs. 3330 g, the difference was not statistically significant (p = 0.743). FMH > 1.8 ml (5 perc) was present in 4.1% of primiparas (42/1023), in 4.2% of secundiparas (44/1050) and in 5.3% of multiparas (18/340), the difference was not statistically significant (p = 0.607). The difference in maternal age, parity, gestational age and birth weight were also not statistically significant for fetomaternal hemorrhage FMH > 2.1 ml (2.5 perc), FMH > 2.5 ml (n = 25), FMH > 5 ml (n = 5). CONCLUSION: Maternal age, parity, gestational age and birth weight does not present a risk factor for excessive fetomaternal hemorrhage during spontaneous delivery.

[Fetomaternal haemorrhage in delivery by cesarean section]. / Fetomaternální hemoragie pri porodu císarským rezem.

OBJECTIVE: To determine the incidence and volume of fetomaternal haemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these parameters would enable optimalization of guidelines for RhD alloimmunization prophylaxis. DESIGN: A prospective cohort study. SETTING: Palacky University Hospital, Olomouc, Czech Republic; University Hospital, Ostrava, Czech Rebublic. METHODS: A total of 4862 examinations were performed. The volume of fetal red blood cell (RBC) entering maternal circulation in normal vaginal delivery (control group, n = 3295) and in delivery by cesarean section (risk group, n = 1567) was assessed by flow cytometry. FMH = fetal RBC volume; fetal blood volume si double (expected fetal hematocrit is 50%). RESULTS: The fetal RBC volume diagnosed in maternal circulation after delivery ranged from insignificant FMH < or = 0.1 ml to excessive FMH = 65.9 ml (median 0.7; mean 0.79; SD 1.38). High values of FMH > 1.7 ml were observed in 5.8% cases (280/4862), FMH > 2.0 ml in 3.2% (157/4862), FMH > 2.0 ml in 1.4% (69/4862) and excessive FMH > 5ml (IgG anti-D insufficient dose 100 microg) in 0.25% (15/4862). Delivery by cesarean section presented a higher risk of incidence of high values of FMH > 1.7 ml (OR 1.6; p 0.0002), FMH > 2.0 ml (OR 2.2; p <0.0001) and FMH > 2.5 ml (OR 2.2; p 0.002) when compared with normal vaginal delivery. It did not, however, present a statistically significant risk factor for the incidence of excessive FMH > 5ml. CONCLUSION: In normal vaginal delivery as well as in delivery by cesarean section, FMH less than 5 ml (10 ml of whole blood) occurs in the great majority of cases, and thus for the prevention of RhD alloimmunization, an IgG anti-D dose of 100 microg should be sufficient. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor.

Demographics, clinical characteristics and outcomes of neonates diagnosed with fetomaternal haemorrhage.

OBJECTIVE: To determine clinical characteristics, demographics and short-term outcomes of neonates diagnosed with fetomaternal haemorrhage (FMH). DESIGN: The authors analysed the Nationwide Inpatient Sample, 1993 to 2008. Singleton births diagnosed with FMH were identified by International Classification of Diseases (ICD-9) code 762.3. Descriptive, univariate and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. RESULTS: FMH was identified in 12 116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and Whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern USA (OR 0.8 vs the Northeastern USA). CONCLUSIONS: Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.

[Minor trauma during pregnancy can cause severe fetomaternal hemorrhage]. / Vuoto sikiöstä äitiin--joskus lievänkin tapaturman vakava komplikaatio.

The principal causes of trauma in pregnancy include falls, motor vehicle accidents and violence. Blunt trauma to the abdomen increases the risk of fetomaternal hemorrhage. Massive fetomaternal hemorrhage is a rare but severe complication which can result in fetal anemia, fetal hypoxia, intrauterine death or neonatal neurologic damage. This case report defines incidence and significance of fetomaternal hemorrhage and shows via two cases that even minor maternal injury can lead to severe fetomaternal hemorrhage and risk of fetal compromise. The most common symptoms of fetomaternal hemorrhage are decreased fetal activity and movements reported by the mother. The cornerstones of evaluation of the third trimester trauma patient after abdominal hit are adequate assessment, CTG monitoring and sonographic fetal surveillance.

Massive fetomaternal hemorrhage secondary to intrauterine intravascular transfusion.

BACKGROUND: Small-volume fetomaternal hemorrhage is frequently observed after intrauterine transfusion. The Kleihauer-Betke test, the reference method for identifying fetomaternal hemorrhage, cannot be used after intrauterine transfusion, because the adult red blood cells used for transfusion cannot be distinguished from maternal red blood cells. CASE: Massive fetomaternal hemorrhage secondary to intrauterine transfusion led to fetal hemorrhagic stroke. We used a method based on blood group identification in the maternal blood to confirm and to quantify fetomaternal hemorrhage. CONCLUSION: Fetal stroke may result from severe hypovolemia and low cerebral blood flow caused by fetomaternal hemorrhage, rather than from fetal anemia itself.

Role of the vascular endothelial growth factor in the inverse relationship between increased nuchal translucency thickness and fetomaternal transfusion.

OBJECTIVE: To elucidate the possible etiological role of the vascular endothelial growth factor (VEGF) in the inverse correlation between nuchal translucency (NT) thickness and fetomaternal transfusion (FMT). METHODS: The level of FMT was determined prospectively in 80 viable, singleton pregnancies in which 10-14-week ultrasonographic scanning, NT thickness measurement; chorionic villus sampling (CVS) for fetal karyotyping and VEGF concentration determination were performed. The grouping procedures were based either on NT thickness (<2 MoM in Group I, and ≥2 MoM in Group II), or on karyotype (euploid in Group A, and aneuploid in Group B). The level of FMT was determined via maternal serum α-fetoprotein levels before and after CVS. The FMT and the VEGF concentration of the chorionic tissue were analysed in comparisons between Groups I and II, and between Groups "A" and "B". RESULTS: The mean level of FMT after CVS was 72.5±21.3 µL and 19.28±5.4 µL in Groups I (n=44) and II (n=36), respectively (P<0.02). The VEGF concentration of the chorionic tissue in Groups I and II was 40.6±16.7 pg/mg protein and 21.1±6.3 pg/mg protein, respectively (P=0.28). The mean level of FMT was 57.9±15.0 µL and 8.1±3.9 µL in Groups A and B, respectively (P<0.003). The VEGF concentration of the chorionic tissue in Groups A and B was 25.9±10.7 pg/mg protein and 21.3±11.3 pg/mg protein, respectively (P=0.77). CONCLUSION: No difference exists in the VEGF concentration in the aspirated chorionic tissue between Groups I and II and between Groups A and B. A higher level of FMT was observed among the aneuploid pregnancies after CVS than among the euploid cases. Chorionic VEGF does not influence the inverse relationship between the pre-CVS NT thickness and FMT.

Significance of the volume of fetomaternal hemorrhage after performing prenatal invasive tests.

BACKGROUND: Fetal erythrocytes cross the placenta during gestation, but invasive prenatal procedures might develop into fetomaternal hemorrhage (FMH). We examine whether flow cytometry immunophenotyping might be useful for measuring the volume of FMH after such procedures. METHODS: Fetal erythrocytes (%) were determined in 153 pregnant women after amniocentesis (129) and chorionic villous sampling (24) using a monoclonal antibody against fetal hemoglobin. Fetal erythrocytes were identified for their high expression of fetal hemoglobin (HbF(++) ). Blood samples from two control groups, 53 healthy males and 21 pregnant women not submitted to invasive tests, were used to establish normal values of circulating HbF(++) erythrocytes in adults. RESULTS: The highest percentage of HbF(++) erythrocytes in the control groups was 0.015%. The rate of HbF(++) erythrocytes in samples after invasive tests ranged between <0.01% and 0.15%. Seventy-three women (47%) had ≤0.015% HbF(++) erythrocytes, and this rate was higher in 80. Nine women presented >1 ml of FMH (volume of packed cells corresponding to 0.054-0.15% HbF(++) erythrocytes), but only two had sonographic evidence of bleeding. CONCLUSIONS: Most women in our series had a very low volume of FMH after the invasive tests. Acute bleeding should be thoroughly investigated in women with either more than 1 ml of packed cells or more than 0.05% of HbF(++) erythrocytes. Intermediate values between >0.015% and <0.05%, should be carefully considered depending on the week of gestation. Data obtained before 15 weeks might reflect previous cell trafficking between fetus and mother instead of acute hemorrhage.