CONCEPTUAL FRAMEWORKS
8.3 CAPTURING THE LEARNING
Fetomaternal haemorrhage has been an intriguing concept over the years since the early 1900’s when erythroblastosis fetalis was first described.5
Various groups all over the world have done different studies on fetomaternal haemorrhage with most of these studies revolving round FMH detection, incidence, antecedent risk factors and management of the alloimmunized pregnancy.
FMH detection has depended on tests which detect red cells containing fetal haemoglobin (HbF) or the detection of Rh D positive fetal red cells in the maternal Rh D negative circulation. In settings where prevention of Rh D alloimmunization is the indication for FMH investigation, then the antibodies to anti-Rh D monoclonal antibodies is useful.7 In other clinical situations, the HbF test must be used. Traditionally, the conventional Kleihauer- Betke test using the acid elution technique has been in use but has been shown to be prone to technical difficulties and associated with poor reproducibility. It is sensitive to pH, time, and temperature. It is also subjective in interpretation of the stained blood film, experience of the scientist/technician performing the test,
assumptions in the calculation of results and increased levels of HbF in maternal red cells during pregnancy.7, 26, 27 These are the shortcomings of using the acid elution technique.
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Quantification of FMH using the flow cytometry testing which allows for large number of cells to be readily counted is now in use. The flow cytometry method involves the use of either anti-fetal haemoglobin labeling or employs the use of the directly conjugated monoclonal anti-D.28, 29 Recent guidelines recommend the flow cytometry process to be more superior to Kleihauer test due to the fact that it is more sensitive, more accurate, allows large number of cells to be readily counted, more objective quantitative results but this is not widely available in developing countries, requires costly equipment and scientists experienced in this methodology.26, 30, 32, 31, 33
Other methods of assaying FMH do exist but are not widely accepted due to varying shortcomings and therefore are only useful in certain experimental circumstances.7, 26, 30, 33 Such other methods include Rosette test, gel agglutination technique, fluorochrome conjugated anti-D with haematology analyses.35, 36, 37, 38 Other surrogate tests in this category which has been reported include enzyme linked anti-globulin test (ELAT), elevation of maternal serum alpha feto-protein (AFP), placental alkaline phosphatase (PLAP),
polymerase chain reaction (PCR), fluorescene in situ hybridization (FISH).30, 34
However, recent guidelines have shown that the acid elution test of Kleihauer is still acceptable where flow cytometry is unavailable but requires
standardized approach to test variables and very prescriptive method.26, 30, 32 It has the following advantages of not being dependent on the presence or
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absence of Rh-D antigen, requires only basic laboratory equipment and inexpensive to perform.26, 30, 32, 33 The following has been recommended for the success of the test; experienced staff, the use of thin blood films, and use of an ocular grid all contribute to more consistent results. In addition the use of control slides and participation in a quality control program are essential.26, 27,
32, 33, 34
Various studies have been done over the years in different populations to assess the incidence and severity of FMH with similar results.8, 9, 27, 39 Severe FMH in most studies has been about 0.3% but in contrast, some other studies have shown a much higher incidence, as much as 4.6% in some.1 Risk factors are similar in most studies but the risk based approach system of screening has failed to identify some cases of Rh isoimmunization. As much as 82% of FMH has been discovered without antecedent risk factors.1, 2 The fact that FMH can occur without antecedent risk factors underscores the importance of further research, and a high index of suspicion, probably, looking in other direction such as placental parameters.10, 12
There has been considerable interest in the study of the human placenta in recent years in order to establish a relationship between placental, maternal and neonatal factors such as birth weight, parity, fetal malnutrition and
anaemia.10 A number of anatomists, embryologists and placental pathologists have shown in recent time that careful examination of the placenta may
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frequently shed light on the aetiopathogenesis of a number of maternal-fetal disorders.14, 15 Recent studies have supported this claim of the placenta being involved in the aetiopathogenesis of some disorders; an abnormally large or small placenta usually indicates the presence of fetal abnormality; a large oedematous placenta suggests intra-uterine infection or blood group incompatibility, while a small placenta is frequently associated with a malnourished or congenitally abnormal fetus.10, 15, 23, 24
In addition to the assessment of placental location, ultrasound can provide an evaluation of placental anatomy. Placental characteristics such as placental thickness and surface area have been determined sonographically.37
Placental weight has been shown to increase significantly from thirty-two weeks and continues beyond until term, while the chorionic surface area appears to increase up to thirty-six weeks, and then remains constant.
Placental thickness has been reported to correlate with and in fact accounts for gain in placental weight. The thickness reflects the amount of parenchyma and the volume of retained intervillous maternal blood. A placenta with normal chorionic surface area at term which is underweight has also been
demonstrated to have reduced thickness.24, 40
Also, the hypoechoeic nature of the placental basal layer in conjunction with the presence of calcification and placental thickness have been used as a system of placental grading which some studies have reported it to predict
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fetal pulmonary maturity.15 However, calcification alone has been difficult to correlate with fetal outcome as results have not been consistent.41
Several groups as reported by Mayhew T. M. (2005)23 have quantified placental morphology during gestation and in a variety of complicated
pregnancies such as pre-eclampsia, intra-uterine growth restriction, sudden infant death, and anaemia. The placenta has been shown to have significant positive correlations with fetal mass.24 Placentomegaly has also been
associated with fetal hydrops.15, 41 Some studies have also shown that multiple gestation, fetal birth weight and complications in labour and mode of delivery of the placenta were significantly associated with risk of FMH.39 Placentas less than 2.5cm thick are associated with intra-uterine growth restriction, while placenta more than 4cm thick have an association with maternal diabetes mellitus, fetal hydrops (of both immune and non-immune aetiology) and intra uterine fetal infections.15, 24 Another study which compared severity of FMH among singleton, twin and triplet pregnancies found a significant increase with that of triplet being 5 times higher than singletons and twice higher than in twin pregnancies. Also, twin gestations were three times higher than singletons.42 These findings suggest that there may be an increase in the feto maternal cell trafficking possibly related to increased placental surface area and
vasculature.42
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Ultrasonography has been documented in various literatures as a relevant non-invasive tool in the management of the Rh-sensitized pregnancy.4, 5 Ultrasound examination of the fetus has become an extremely important adjunct for antepartum fetal surveillance. It has been used to monitor severity of erythroblastosis fetalis and reduce the need for invasive procedures.
Sonographic features such as polyhydramnios, placental thickness greater than 4 centimetres, pericardial effusion, dilatation of the cardiac chambers, chronic enlargement of the spleen and liver, visualization of both sides of the fetal bowel wall and dilatation of the umbilical vein have all been proposed as indicators of significant prehydropic fetal anaemia.5
Also, during invasive sampling procedures and intrauterine blood transfusion processes on the sensitized fetus, ultrasound guided procedures have been shown to dramatically reduce the procedure related morbidity and mortality associated with these procedures.5
Doppler velocimetry, a more recent investigative tool which is based on the phenomenon that occurs when a source of light or sound waves is moving relative to an observer, the observer detects a shift in the wave frequency. In obstetrics, Doppler has been used to determine the volume and rate of blood flow through maternal and fetal vessels. Two types of doppler velocimetry are in use in medical practice; continuous wave doppler and pulse wave doppler.
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Various combinations of these are commercially available and are referred to as Duplex Doppler.5
Doppler flow velocity waveforms have been extensively investigated as non invasive predictors of fetal anaemia and acidosis. Fetal cardiac output and blood velocities in the umbilical artery, umbilical vein, fetal descending aorta, fetal ductus venosus, fetal splenic artery, and fetal middle cerebral artery have all been studied in alloimmunized pregnancies.5 Of all these vessels, the measurement of the peak systolic velocity of the fetal middle cerebral artery has been shown to be the most sensitive tool for predicting moderate to severe fetal anaemia in order to determine appropriate timing of delivery.4, 5 Currently, the American College of Obstetrics and Gynaecology considers middle cerebral artery doppler velocimetry as a tool for antepartum fetal
surveillance in the management of the already Rh- sensitized fetus.4 It has the disadvantage of a false positive rate of twelve percent, apart from being
expensive, not widely available and not predictive of the risk of fetomaternal haemorrhage.
Limited studies were found in the literature assessing ultrasound as a
predictive tool for fetomaternal haemorrhage. This study aims at determining whether placental parameters (using ultrasound assessment) can be a
determinant of fetomaternal haemorrhage.
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