Figure 2: Fetal hemoglobin (light gray area) and transfusions (+ = transfusions of packed red cells, - = withdrawals of fetal blood). The top gray area is the lower range of normal values for age, truncated at 12 g/dl13).
Three days later a repeat ultrasound showed improvement of the fetal hydrops. There was no ascites or pleural effusion and only a small amount of fluid in the pericardial sac. Fetal hemoglobin was 2.5g/dL. A repeat intrauterine transfusion of 18ml, lifted the hemoglobin to 6.7g/dL. A further Kleihauer‑Bethke test suggested 12ml of fetal blood in the maternal circulation.
The following day the fetal hemoglobin had fallen again to 2.7g/dL. Thirty‑five ml of packed red cells was infused and 8ml removed. This resulted in a fetal hemoglobin of 9.0g/dL. Two days later (at 23 weeks and 1 day gestation) the fetal hemoglobin was 3.3g/dL. A 40ml packed red cell transfusion was given and 31ml removed. Post‑transfusion hemoglobin was 10.5g/dL.
At 23 weeks and 6 days gestation fetal hemoglobin had at last stabilized at 9.3g/dL, indicating cessation of hemorrhage. Mild dilatation of the cerebral ventricles with a thin rim of fluid under the skull bones was detected. Two weeks later the fetus had demonstrated normal growth. There was dilatation of the left atrium of the lateral cerebral ventricle at 11mm. The atrium on the right measured 9mm. No hydrops was present. Mild ventricular dilatation was again noted at 29 and 31 weeks, but hydrops did not recur.
At 34 weeks the estimated fetal weight was 1800g (on the 20th percentile), indicating some reduction in the rate of growth. Ventricular size was now normal. There was also a mild reduction in amniotic fluid volume. In light of this suspected intrauterine growth retardation, the patient was induced at 37 weeks" gestation.
A 1mg prostaglandin E2 pessary was inserted in the early evening. The following morning amniotomy was performed and an oxytocic infusion was administered. After 5 hours the patient was fully dilated and a 12 minute second stage resulted in the normal delivery of a live born female babe weighing 2185g. The birthweight equated to the 3rd percentile for gestational age. The placenta was adherent and was manually removed "piecemealâ€. Neurologically, the baby was clinically normal both at birth and at six week review. A cranial ultrasound performed the day after birth was normal with no features of hydrocephalus. The head circumference at birth was 31cm (equal to the 3rd percentile).
In the case presented here, there was no apparent cause of the fetomaternal hemorrhage. Fetomaternal hemorrhage may be precipitated by:
external cephalic version,
rapid reduction in uterine size (e.g. following the birth of the first twin),
spontaneous placental abruption of unknown cause.
The classical features of fetal hydrops have previously been reported in association with this condition2‑4.
Investigations which should be considered in the presence of idiopathic fetal hydrops include:
blood group iso‑antibody screen,
alpha‑thalassemia screen, and a
detailed ultrasound scan of fetal and placental morphology.
In confirming the diagnosis of fetomaternal hemorrhage, the Kleihauer‑Bethke test remains the gold standard. Other methods of investigation that have been tried include the "Microscopic Du" test (enhanced by Polyethylene Glycol), flow cytometry and rosette testing. The rosette test may be more sensitive11. There is a report of a false positive Kleihauer‑Bethke test due to persistent elevated maternal hemoglobin F12. The Kleihauer‑Bethke test offers the advantage of being a qualitative and quantitative test. The gestation and size of the fetus must be given some consideration when interpreting the quantitative result. Also, the possibility of chronic ongoing fetomaternal hemorrhage should be considered.
Persistent fetomaternal hemorrhage has been described in which transfusions were unable to "keep upâ€ with the ongoing blood loss2. However, at a gestation of 22 weeks as in this case report, immediate delivery was not an option. Fortunately, the fetomaternal hemorrhage in this patient did not persist and thereby allowed the pregnancy to progress until term.
It is of interest to consider how the fetus may cope with an insult severe enough to reduce its hemoglobin below 3g/dL. Probable mechanisms include:
An increase in peripheral vascular resistance, restoring mean arterial blood pressure within minutes. This is probably mediated by increased catecholamines and renin secretion.
Maintenance of ductus venosus derived blood flow to the brain and heart at the expense of a reduction of such flow to lungs, gut, kidneys and periphery.
Restoration of circulating volume from the extravascular space and/or placenta.
These mechanisms have been well demonstrated in fetal sheep by Myers et al5.
A new issue raised in this case report is the possible impact of the fetomaternal hemorrhage on the central nervous system. Ventricular dilatation was confirmed on three separate ultrasound examinations. This asymmetrical dilatation of the ventricular atria was probably a consequence of the acute hypoxic event. The fetal central nervous system appears to have demonstrated a remarkable plasticity in recovering to a normal anatomical appearance and symmetry in less than 5 weeks from the last intrauterine transfusion. Long‑term sequelae of fetal hemorrhage have been previously reported in a case of acute twin‑twin transfusion, in which cystic lesions developed in the brain of the surviving anemic twin6.
Presentations of fetomaternal hemorrhage at later gestations have included the finding of a sinusoidal pattern on the cardiotocograph3,7,8,9. In the case presented, fetal anemia had been corrected by 28 weeks gestation, at which time fetal heart‑rate monitoring became appropriate.
Another uncommon but important method by which fetomaternal hemorrhage can present is by a raised maternal serum alpha‑fetoprotein level4,9. An acid elution test should be considered in this situation, bearing in mind other common causes of a raised serum alpha‑fetoprotein such as neural tube and abdominal wall defects, twins, renal agenesis, urinary tract infection and parvovirus infection4.
Intra‑uterine transfusion is not without risk to the fetus. The addition of an acute volume load to an already compromised circulation can result in severe fetal distress requiring urgent delivery if gestational age permits10. In this patient, following the third transfusion a fetal bradycardia of 80 beats per minute was observed for 4 minutes prior to returning to normal.
This case adds to previous reports that intrauterine transfusion can be a life‑saving procedure in cases of acute fetomaternal hemorrhage2,3,4,8. Fortunately in this case, hemorrhage eventually ceased spontaneously, but such is not always the case2,7,8. Early delivery may be preferred to intrauterine transfusion at gestational ages compatible with survival. Early neonatal resuscitation with packed red blood cells may be required in such circumstances7.
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2.Llaube DW, Schauberger C.W. Fetomaternal Hemorrhage: A major cause of intra uterine death. Obstet Gynecol 60: 649‑51, 1982.
3. Rouse D, Weiner MD. Ongoing Fetomaternal hemorrhage treated by serial fetal intravascular transfusions. Obstet Gynecol 76: 974‑976, 1990.
4. Gilbert WM, Scioscia AL. Spontaneous fetomaternal hemorrhage resulting in hydrops and elevated maternal serum alpha‑fetoprotein. J Ultrasound Med 10: 645‑8, 1991.
5. Meyers, Paulick, Rudolph C, Rudolph A. Cardiovascular response to acute severe hemorrhage in fetal sheep. J Dev Physiol 15: 189‑197, 1991.
6. FusI L, McFarland P, Fisk N, Wigglesworth J: Acute twin‑twin transfusion. A possible mechanism for brain‑damaged survivors after intra‑uterine death of a monochorionic twin. Obstet Gynecol 78: 517‑20, 1991.
7. McHugh J, Davidson DH. Fetomaternal hemorrhage with decreased fetal movements and a sinusoidal fetal heart rate pattern. NZ Med J 104: 426‑7, 1991.
8. Fischer RR, Kuhlman K, Grover J, Montgomery O, Wapner R. Chronic massive fetomaternal hemorrhage treated with repeated fetal intravascular transfusion. Am J Obstet Gynecol 162: 203‑4, 1990.
9. Boyd PA. Why might maternal serum AFP be high in pregnancies in which the fetus is normally formed. Brit J Obstet Gynecol 99: 93‑5, 1992.
10. Elliot P. Massive fetomaternal hemorrhage treated by fetal intravascular transfusion. Obstet Gynecol 78: 520‑3, 1991.
11. Bayliss KM, Kueck BD, Johnson ST, et al. Detecting fetomaternal hemorrhage; a comparison of five methods. Transfusion 31: 303‑7, 1991.
12. Weaver DN., Barthold JC, Hamill B, Sharp GH, Tindle BH. Hereditary persistence of fetal hemoglobin presenting as fetomaternal hemorrhage. Am J Clin Pathol 93: 277‑80, 1990.
13. Kypros H. Nicolaides: Fetal blood analysis.Ultrasound in obstetrics and gynecology. Chervenak F, Isaacson G, Campbell S (Eds). Little Brown (Boston) 1993. p 1792.