Foeto-maternal Haemorrhage Research Articles

Routine maternal ABO/Rhesus D blood typing can alert of massive foetomaternal haemorrhage.

Spontaneous massive foetomaternal haemorrhage (SM-FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM-FMH. Retrospective analysis of medical records from neonates born at our tertiary, university-affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM-FMH was based on neonates born with severe anaemia (haematocrit [HCT] <15%) within the first 24 h post-delivery with positive maternal Kleihauer-Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM-FMH. Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM-FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM-FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.

Partial Exchange Transfusion in the Management of a Preterm Neonate with Severe Anaemia from Acute Foetomaternal Haemorrhage: A Case Report

Foetomaternal Haemorrhage (FMH) refers to the passage of foetal blood into the maternal circulation. FMH is rarely diagnosed antenatally as clinical findings are subtle and non specific. Massive FMH is suspected when foetal movements are decreased, and Cardiotocographic (CTG) findings are abnormal with decreased heart rate variability, saw-tooth or a sinusoidal pattern. Massive FMH can lead to foetal demise, stillbirth, hydrops, or the birth of a severely anaemic infant with hypovolaemic shock. A 35-week pregnant woman presented with decreased foetal movements, and an emergency caesarean section was performed due to late deceleration on the cardiotocograph. The baby was very pale at birth and in shock. The Kleihauer-Betke (KB) test performed on the mother’s blood shortly after delivery showed 2.7% foetal red cells, suggesting 135 cc of FMH. The clinical features and outcome of FMH depend on the gestational age, volume, and rapidity of FMH, as well as, whether it is acute or chronic. Packed cell transfusion is recommended, but in babies with severe anaemia and cardiac failure, partial exchange transfusion is performed. The baby was managed with a fluid bolus, inotropic support, respiratory support, and partial exchange transfusion, resulting in a successful outcome. A high index of suspicion enables the obstetrician to undertake diagnostic tests, cordocentesis, plan for intrauterine transfusion or delivery, and alert the neonatal team for a better outcome.

English

BACKGROUND Entry of foetal erythrocytes into maternal circulation before or during delivery is referred as Foetomaternal Haemorrhage (FMH). An Rh-D negative women when exposed to the cells of an Rh-D positive foetus, produces anti-D antibodies that causes complications like foetal anaemia, hydrops foetalis and neonatal jaundice. The Kleihauer-Betke test is a quantitative test, which uses the concept of differential resistance to acid by foetal and adult haemoglobin. As the potential risk factors can be determined by placental morphology and provide information on pregnancy outcome, they may provide information on incidence and amount of FMH also.The objective of this study is to determine the relationship between placental parameters (weight and diameter) and the incidence as well as severity of Foetomaternal Haemorrhage (FMH). The secondary aim was to correlate FMH with maternal factors and neonatal anaemia.MATERIALS AND METHODS A total of 333 women who delivered in the hospital after 28 weeks of gestation were enrolled for the study. Maternal blood (2 mL) was collected in EDTA bottle after the delivery of the baby. Samples were sent to Blood Bank. FMH was quantified by Kleihauer-Betke’s test. The foetomaternal haemorrhage is calculated as: Number of foetal cells per high power field/Number of maternal cells per high power field x 2400.1 FMH > 2 mL was considered positive for FMH as per BSCH (British Committee for Standards in Haematology) guidelines.2 Placental parameters like weight (after trimming cord at 5 mm from the insertion point and clearing membranes, clots) and diameter were measured. A cut-off of 500 gms for placental weight and 22 cm for placental diameter was taken.3,4,5 Actual birth weight and neonatal Haemoglobin (Hb) was noted.BSCH = British Committee for Standards in Haematology.RESULTS Out of 333 subjects 48 (14.4%) were positive for FMH (Group 1) and 285 (85.6%) were negative for FMH (Group 2). The mean placental weight (508.54 ± 80.34 gm) and the mean placental diameter (19.92 ± 3.99 cm) were significantly more in patients having positive FMH when compared to those with negative FMH. (P value = 0.0005 for placental weight and p = 0.005 for placental diameter). When placental weight was ≥ 500 gm more subjects were significantly positive for FMH (25.6%) compared to when that was less than 500 gm (7%) (P value = 0.00). When the placental weight was between 600 and 699 gm, the odds of having FMH was 13.43 times more. When the placental diameter was ≥ 22 cm, the incidence of positive FMH was significantly more (33.9%) compared to when that was 2 mL both mean placental weight (508.54 ± 80.34 gm) and diameter (19.92 ± 4.00 cm) were significantly higher when compared to lesser FMH. (P value 0.00 for both weight and diameter). Incidence of positive FMH was significantly more in maternal risk factors such as GDM, preeclampsia, placenta previa. The odd of having positive FMH was 16.45 times more in the presence of placenta previa. There was a mild negative correlation coefficient existed between the neonatal haemoglobin and amount of FMH, which was statistically significant (p value = 0.000). That means although neonatal anaemia was not found in the babies in our study, there was a trend of having lower haemoglobin with higher FMH.CONCLUSION With the findings of present study, it was concluded that bigger the placenta in terms of weight and diameter more is the foetomaternal haemorrhage. Foetomaternal haemorrhage is associated with maternal complications such as multifoetal gestation, GDM, preeclampsia and a diagnostic test for FMH should be considered in such cases to detect neonatal anaemia at the earliest possible and to decide on adequate dose of anti-D to clear the foetal cells from maternal circulation.

Anti-D Prophylaxis Reviewed in the Erea of Foetal RHD Genotyping

A few years ago, the prevention of anti-D immunization was currently based on systematic postnatal prophylaxis associated with targeted antenatal injection in high-risk situations of foeto-maternal haemorrhage. The failures of prevention are mainly due to the non-respect of established guidelines for RhIG prophylaxis, and to spontaneous undetected foetal-maternal haemorrhages without any obvious cause during the third trimester of pregnancy. In order to reduce the rate of residual post-pregnancy anti-D immunization, several countries decided to associate the classical prophylaxis to a routine antenatal anti-D prophylaxis (RAADP) during the 28th or 29th week of gestation. Since about ten years, the foetal RHD genotyping in maternal plasma enables us to limit the antenatal prophylaxis only to those D- women carrying a D+ foetus. This paper deals with: the advantages of an antenatal prevention in the light of non invasive foetal RHD genotyping, the rules rendering prevention protocols efficient whatever the algorithm applied, and the recommended immuno-haematology follow-up of women who have received RhIG.

The prevalence of maternal F cells in a pregnant population and potential overestimation of foeto-maternal haemorrhage as a consequence.

Acid elution (AE) is used to estimate foeto-maternal haemorrhage (FMH). However AE cannot differentiate between cells containing foetal or adult haemoglobin F (F cells), potentially leading to false positive results or an overestimate of the amount of FMH. The prevalence of F cells in pregnant populations remains poorly characterised. The purpose of this study was to ascertain the incidence of HbF-containing red cells in our pregnant population using anti-HbF-fluorescein isothiocyanate flow cytometry (anti-HbF FC) and to assess whether its presence leads to a significant overestimate of FMH. Eighty-eight pregnant patients were assessed for the presence of F cells and foetal red cells by AE and anti-HbF FC. The "FMH equivalent", estimated by AE and anti-HbF FC, was calculated. Thirty-six percent of the pregnant population had F-cell populations detectable by anti-HbF FC while AE detected F cells in 48% of the population. The mean estimated FMH equivalent determined by AE and anti-HbF FC was 0.59 mL (0-23.93 mL) and 0.41 (0 to 2.19 mL), respectively (p=0.012). In 3% of our population, AE overestimated the FMH by >3 mL due to the presence of an F-cell population of at least 16%. Thirty-six percent of a prospectively evaluated group of consecutive pregnant women were found to have F-cell populations. In some patients, these findings were clinically significant as AE overestimated the degree of FMH as a consequence.

Foetomaternal Haemorrhage (FMH): A Case for Routine Screening

Background: Foetomaternal haemorrhage (FMH) over the years has been a matter of a major concern as it occurs asymptomatically and is one of the most common disorders responsible for foetal death. FMH occurs when there is leakage of foetal blood into maternal circulation due to breach in the physiological barrier between their circulations. In most pregnancies about 0.1ml foetal bleed occurs and it could be acute or chronic. The detection and quantification of any quantity of foetal red blood cells in maternal circulation would be important for obstetrical management of pregnant women. But FMH is not part of the routine screening done for pregnant women in many areas. Aims/objectives: The aim of this study was to assess the prevalence of FMH among pregnant women attending antenatal clinic in a District Hospital towards recommending the testing as part of the routine screening of pregnant women. Methods: A Kleihauer-Betke test (KBT) was used to quantify foetal red blood cells in venous blood from 212 expectant mothers recruited for the study. Thin blood smear (film) was prepared, dried, fixed, incubated in an acid solution and stained with eosin. They were then examined under the microscope. The foetal cells were counted and reported as a percentage of the adult cells and the FMH was calculated from that. Antibody screening was also done using the Coombs indirect test. Results: There was FMH prevalence rate of 0.5% when the cut-off of FMH was 30.0 ml. Also, 2% of the study group had antibodies in their serum. Conclusion: with the majority of the study population showing FMH below the level that could harm the foetus, it can be concluded that, the screening may not be mandatory but all at risk (rhesus negative) women should be screened routinely.

Evaluation of a new rapid anti‐HbF FITC assay, Trillium QuikQuant, for detection and quantitation of foetomaternal haemorrhage

This study evaluated a new product for flow cytometric foetomaternal haemorrhage (FMH) quantitation, Trillium QuikQuant anti-HbF FITC kit (Trillium Diagnostics, USA), in comparison with the Millipore anti-HbF FITC method. Blood from 67 antenatal or postpartum RhD-negative women together with 108 samples spiked with 0.2%, 0.4%, 0.6%, 2%, 4%, 5%, 6%, 8% and 10% of foetal red cells were analysed by both methods. Results for both methods were linear to 10% foetal red cells. Analysis using the Wilcoxon test found that there was no difference between the paired results of Trillium QuikQuant and the expected values of the spiked samples (P=0.48). In contrast, Millipore anti-HbF FITC gave statistically higher results compared with both the expected values and Trillium QuikQuant anti-HbF FITC (P=0.0003 and P<0.0001, respectively). The Bland-Altman plot for Trillium QuikQuant showed a mean difference of only 0.06% below the expected values, whilst Millipore was 0.13% above. The analysis time with Trillium QuikQuant was approximately 40min, requiring significantly less hands-on time than the Millipore method that required an additional four wash steps. Trillium QuikQuant is a new precise, accurate and rapid flow cytometric kit method for the quantitation of FMH in both the antenatal and postpartum period.

Outcome of external cephalic version in breech presentation

Breech presentation is the most common abnormal foetal presentation with an incidence of 3–4% at term. It is associated with increased perinatal mortality and morbidity irrespective of the route of delivery. There is higher incidence of premature rupture of membranes, premature labour, prolapsed cord, traumatic deliveries, perinatal mortality and morbidity including various birth injuries, which makes breech an unfavourable presentation. Not only is the foetal asphyxia more commonly seen in breech, the incidence of traumatic morbidity like intracranial haemorrhage, visceral injuries, fractures, dislocations, and peripheral nerve injuries are encountered more frequently.1 With the passage of time, the art of assisted breech delivery has suffered significant setback. Most of the cases of unfavourable presentation like breech are subjected to caesarean section in the current obstetric practice. The elective caesarean section does not guarantee the improved outcome of the baby and may also increase the risk for the mother, compared to vaginal delivery.2 This situation is further compounded by current small family norms and fear of litigation. In view of this, converting an unfavourable presentation like breech into cephalic presentation by carrying out an external cephalic version (ECV) is a viable option. With ECV the expected 3–4% incidence of breech presentation at delivery may be reduced to 1%. Besides, ECV may also protect against premature labour, its complications, and permit a higher percentage of term deliveries as 20–30% of obstetric patients with breech presentation deliver prematurely.3 External cephalic version is also a potentially hazardous procedure. There is increased risk of ante partum haemorrhage, foeto-maternal haemorrhage, and foetal distress, rupture of membranes, placental abruption, and cord complications. External cephalic version is a strong stimulant of foeto-placental unit as evident by increased middle cerebral arterial blood flow and increased cell free foetal deoxyribonucleic acid in maternal circulation. In the hands of an experienced surgeon and with aid of tocolytics, ultrasonography, and cardiotocography the overall success rate of the procedure is 77% with very small risk of complications.4 Moreover, low cost, ease of procedure, and patient preparation are the added advantages. The delay to attempt ECV at or after 37 weeks of gestation has obvious advantages like management of complications by emergency caesarean section, giving time for spontaneous version to take place with the requirement of fewer procedures.5,6 Thus, there are some uncertainties related to the role and outcome of ECV in breech presentation. The present study aims to determine the outcome of ECV in breech presentation.

Editorial: Alternative approaches to breech presentation

Editorial: Alternative approaches to breech presentation

RH D FOETO-MATERNAL ALLOIMMUNIZATION PROPHYLAXIS WITH ANTI-D IMMUNOGLOBULINS REVIEWED IN THE ERA OF FOETAL RHD GENOTYPING

In Belgium, prevention of anti-D immunization is currently based on systematic postnatal prophylaxis associated with targeted antenatal injection in high-risk situations of foeto-maternal haemorrhage. The failures of prevention are mainly due to the non-respect of established guidelines for RhIG prophylaxis, and to spontaneous undetected foetal-maternal haemorrhages without any obvious cause during the third trimester of pregnancy.In order to reduce the rate of residual post-pregnancy anti-D immunization, several countries decided to associate the classical prophylaxis to a routine antenatal anti-D prophylaxis (RAADP) during the 28th or 29th week of gestation. Since a few years, the foetal RHD genotyping in maternal plasma enables us to limit the antenatal prophylaxis only to those D- women carrying a D+ foetus.This paper deals with: the advantages of an antenatal prevention in the light of non-invasive foetal RHD genotyping, the rules rendering prevention protocols efficient whatever the algorithm applied, and the recommended immuno-haematology follow-up of women who received RhIG.

Suivi immunohématologique des femmes enceintes : nouvelles recommandations

Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins over 40 years, fetomaternal incompatibility due to RH1 antigen (RhD) is not completely eradicated, although perinatal consequences might be extremely serious. Additionally, allo-immunizations against other antigens, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell), may cause severe haemolytic disease. Follow-up of allo-immunization during pregnancy and its prevention are therefore still a concern for all pregnant women. Immunohaematological tests used in antenatal patients are under practice for a long time. However, despite significant progress, it is clear that these tests provide only an indirect indication and will only help the obstetrician, in conjunction with over fetal parameters, to assess the severity of the haemolytic disease. Since almost two decades, fetal RHD genotyping became a reality, first using amniocytes, but more recently by analyzing fetal DNA present in the maternal plasma. RH prophylaxis concerns RH:-1 women, who are non-sensitized against RH1 antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis includes targeted prophylaxis after foetomaternal haemorrhage and now routine antenatal RH prophylaxis at 28 gestation weeks. Indications for RH prophylaxis and immunohaematological testing to assure an efficient therapeutic prevention have been summarized in France through specific recommendations of the National College of Gynecologists and Obstetricians.

False positive Kleihauer results: an unusual cause in a postnatal patient in remission from acute myeloid leukaemia

A 34-year-old woman, in remission from acute myeloid leukaemia, had a positive postnatal Kleihauer result. Following our standard local protocol for positive Kleihauer tests in Rh-D negative patients, the specimen was referred for confirmatory testing, which proved the result to be false positive. Hereditary persistence of foetal haemoglobin was excluded as a Kleihauer test performed in a pregnancy prior to the development of leukaemia was negative. Further testing confirmed mild elevation of foetal haemoglobin (HbF) and increased F-cells. Elevated-HbF levels have been widely reported in patients with haematological malignancy. In this case, the patient was confirmed to be in a true molecular remission from leukaemia and yet appeared to have a residual clonal population of HbF erythrocytes; the significance of this finding remains unclear. This case also highlights the importance of confirmatory testing of suspected foeto-maternal haemorrhage, as not all positive Kleihauer tests are true positives.

The issue of Anti-D: An integrated seamless approach from recognition of need to bedside administration

The appropriate and timely administration of Anti-D immunoglobulin to Rhesus (D) negative women who have delivered Rhesus (D) positive babies is a vital part of obstetric care. Anti-D has an especially high profile in Ireland because of the tragic inadvertent transmission of Hepatitis C to Irish women in past decades. We have reviewed our policy and procedures pertaining to the administration of Anti-D for sensitising events during pregnancy and postnatally, in the Mid-Western Health Board in 1999/2000. As a result, major changes were made in the storage, issue, recording and administration of Anti-D. New procedures in the transfusion laboratory and in the maternity hospital have been accepted by scientists and midwives and supported by haematology and obstetric medical staff. The pharmacy and haematology laboratory no longer have a role in this programme. IMPLEMENTATION OF MULTI-DISCIPLINARY CHANGE MANAGEMENT: As a result of these changes, the storage, issuing and tracking of Anti-D has become the responsibility of the hospital blood bank. Measurement offoeto-maternal haemorrhage (FMH) is now the responsibility of bio medical scientists in blood bank, utilising both flow cytometry (increasingly recognised as the gold standard method) and the Kleihauer method (Kleihauer-Betke). The programme has moved from a doctor-administered IV Anti-D Ig, to a midwife-administered IM preparation. Prescription remains the responsibility of the doctor. These changes are facilitated by the protocol guided issue of the appropriate dose of Anti-D Ig by bio medical scientists to midwives. The issue of the Anti-D Ig occurs simultaneously with issue of results of mother and baby's serology testing and estimation of volume of FMH. These major changes have been guided by audit and needs assessment and require close liaison between medical, nursing and laboratory scientific staff in haematology, transfusion and obstetrics. CRITICAL INCIDENT AUDIT-CASE REPORT: Before new procedures became official policy, a critical incident audit allowed us to pilot our protocol and to revise it using draft new procedures. In this critical incident we describe successful management of a patient with a large foeto-maternal haemorrhage. This incident supported the need for the procedural enhancements already underway. This critical incident re-emphasised the need for the planned systems improvements to be introduced quickly.

Immunocytometric quantitation of foeto-maternal haemorrhage with the Abbott Cell-Dyn CD4000 haematology analyser

This study evaluated the extended use of a haematology analyser (Abbott Cell-Dyn CD4000) for the immunofluorescent enumeration of foeto-maternal haemorrhage (FMH) with fluorescein isothiocyanate-labelled monoclonal anti-RhD. Method performance was assessed with artificial FMH standards, and a series of 44 clinical samples. Within run precision was <15% (coefficient of variation, CV) for FMH volumes of 3 ml and above, 18.8% at an FMH volume of 2 ml and 31.7% at an FMH volume of 1 ml. Linearity analysis showed excellent agreement (observed FMH% = 0.98x expected FMH% + 0.02), and a close relationship (R(2) = 0.99) between observed and expected FMH percentages. The lower limit of quantification of the CD4000 (SRP-Ret) method with a maximum CV of 15% was 1.6 ml, and the limit of detection was <1 ml. Parallel Kleihauer-Betke test (KBT) assessments of FMH standards showed an overall trend for higher KBT values (observed = 1.25x expected - 0.38). At an FMH level of 4 ml, KBT observer estimates ranged from 0.57 to 11.94 ml with a mean inter-observer CV of 63%. For 44 clinical samples, there was decision point agreement between KBT and SRP-Ret results for 42 samples with an FMH of <2 ml. Analysis in the low FMH range (<1 ml) showed that small volume foetal leaks could be detected with the SRP-Ret method in most of 23 samples with negative KBT results. CD4000 SRP-Ret method performance for FMH determination was similar to that reported for flow cytometry.

Massive foetomaternal haemorrhage associated with a favourable outcome after two years Sir

Massive foetomaternal haemorrhage associated with a favourable outcome after two years Sir

Simultaneous choriocarcinoma in mother and newborn infant

A male infant, born following an uncomplicated pregnancy, was severely anaemic at birth following significant foeto-maternal haemorrhage. At three weeks of age a tumour was found in the liver with evidence of metastatic disease in the lungs. The infant died before treatment could be started. Postmortem revealed choriocarcinoma which led to subsequent diagnosis in the mother who also had pulmonary metastases. The mother has been successfully treated. The case is described in detail and followed by a discussion and a literature review of reported cases of simultaneous choriocarcinoma in infant and mother.

Elevation of maternal alphafoetoprotein serum levels in relation to foetomaternal haemorrhage after second-trimester pregnancy termination by aspirotomy

Elevation of maternal alphafoetoprotein serum levels in relation to foetomaternal haemorrhage after second-trimester pregnancy termination by aspirotomy

Elevated maternal αFP due to foeto-maternal haemorrhage

Elevated maternal serum levels of α-foetoprotein have been used as a screening procedure in the prenatal diagnosis of foetal neural tube defects where levels about the 98th percentile are indications for further testing. False positives due to multiple pregnancies, threatened abortions and incorrect gestations are well documented, however many false positives remain unexplained. In a survey of 150 women who gave birth to normal infants, 11/69 (16%) of women with anterior placentas revealed elevated maternal αFP levels associated with increased numbers of foetal cells. This suggests that foeto-maternal haemorrhage in an otherwise normal pregnancy can account for a percentage of raised αFP levels. The use of Kleihauer technique would eliminate elevated αFP levels due to foetomaternal haemorrhage that appears to be prevalent in women with anterior placentas.

Fréquence et importance des hémorragies fœto-maternelles par amniocentèse précoce

Amniocentesis is a technic to which it is now made more and more reference, even when feto-maternal incompatibility is not involved, for many various indications and at variable chronology along pregnancy. Our study concerns the risk developing Rh immunization among Rh negative women, undergoing amniocentesis early in pregnancy. 233 women had 243 amniocentesis between 16 and 21 weeks of pregnancy. Fetal cells in the maternal circulation were searched for using the Kleihauer's acid elution technic. In 154 cases, the Kleihauer's method was also used just before the amniocentesis, in order to run out a spontaneous foeto-maternal haemorrhage and to correlate the 25 (16,2%) transplacental haemorrhage reported to amniocentesis. When ever the result was positive, we observed a feto-maternal ratio varying from 1/20 000 to 100/20 000 but it is very difficult at this early period of fetal life to assure a precise volume of blood from this ratio. Placental localization preceeding amniocentesis does not seem minimizing the risk of bleeding. Althrough the occurence of a fetal bleeding seems to be more frequent in cases where blood can be demonstrated in the amniotic fluid (8/25 = 32%) than in cases it is not, the estimated volume of the foeto-maternal haemorrhage is not related to the presence or absence of blood in the amniotic cavity. In 3 cases the intra-amniotic blood was tested by the Kleihauer's method. In two instances there was a mixture of adult and fetal cells. In the 3rd case only fetal cells were present. In this last case, as in 17/25 bloody amniotic fluid (68%) no feto-maternal haemorrhage could be demonstrated. The risk of Rh immunization commands prophylaxis. In such Rh negative women, we inject intravenously a 85 mug dose of anti-D immunoglobulin, soon after performing amniocentesis, what ever the result of Kleihauer test is positive or negative.

A method of calculating the volume of transplacental foetomaternal haemorrhage.

Summary. A simple procedure for foetal red cell counting and determining the ratio of foetal red cells to adult red cells is described. Kleihauer's formula for converting the ratio of foetal cells to adult cells into the absolute volume of transplacental haemorrhage was found to give reliable results in a biological trial in which samples of cord blood were injected into 19 patients.