A very preterm infant born to mother of mirror syndrome secondary to fetomaternal hemorrhage: a case report.

BACKGROUND: Mirror syndrome (MS) is defined as maternal edema with fetal hydrops and placental edema with different etiologies, such as rhesus isoimmunization and twin-twin transfusion syndrome. Herein, we showcased a unique MS case secondary to fetomaternal hemorrhage (FMH). CASE PRESENTATION: A 32-year-old gravida 2 para 0 woman diagnosed with fetal hydrops was admitted to our hospital. Maternal laboratory tests revealed anemia, slightly increased creatinine and uric acid levels, hypoproteinemia, and significantly increased alpha-fetoprotein and hemoglobin-F levels. Therefore, FMH was diagnosed initially. Two days after admission, the woman had unexpectedly progressive anasarca and started to feel chest distress, palpitations, lethargy, and oliguria, and MS was suspected. An emergency cesarean section was performed to terminate the pregnancy. The maternal clinical symptoms and laboratory tests rapidly improved after delivery. A very preterm infant with a 2080-g birthweight at 31 weeks gestation survived after emergency cesarean section, active resuscitation, emergency blood transfusion, abdominocentesis, and advanced life support. CONCLUSIONS: FMH could develop into MS, providing new insights into the etiology of MS. Once MS is diagnosed, emergency cesarean section might be an alternative treatment. The very preterm infant survived with a favorable long-term outcome, and a well-trained perinatal work team is needed for such cases.

The Recurrence Risk of Fetomaternal Hemorrhage.

Massive fetomaternal hemorrhage (FMH) can cause devastating pregnancy outcomes. Perinatal prognosis may be improved by intrauterine transfusion, but the appropriate management for these pregnancies remains unclear. To determine the recurrence risk of FMH after intrauterine transfusion, we performed a systematic review of all case reports/series of patients with proven FMH treated with intrauterine transfusion and who had subsequent follow-up of at least 72 h until delivery. This revealed 13 cases, with 1 additional case from our institution. Ten patients (71.4%) had a second episode of FMH requiring a second intrauterine transfusion. Five patients (35.7%) required at least 3 intrauterine transfusions. The time interval between intrauterine transfusions was progressively reduced. The gestational age at the onset of signs/symptoms was 26.6 ± 2.1 weeks, and gestational age at delivery was 34.2 ± 4.2 weeks. Two cases of fetal demise (14.3%) and no neonatal deaths were recorded. Limited postnatal follow-up on 8 neonates was normal. The mean neonatal hemoglobin and transfusion rates were 13.2 ± 5.7 g/dL and 33.3%, respectively. Close fetal monitoring, likely daily, is necessary to recognize FMH recurrence. Several transfusions may be necessary once FMH is diagnosed if pregnancy is allowed to continue > 72 h.

Establishing the Cause of Anemia in a Premature Newborn Infant.

The three major causes of anemia in neonates are blood loss, decreased red blood cell production, and increased degradation of erythrocytes. Establishing the cause of anemia in a neonate born prematurely can be challenging. Clinically, fetomaternal hemorrhage (FMH) can be difficult to diagnose-the condition often presents only after the manifestation of severe fetal anemia. FMH can be confirmed by determining the fetal hemoglobin F fraction in the mother, which is traditionally performed using the Kleihauer-Betke test (KBT). Herein, we present a case study of a newborn baby boy of Dutch ethnicity with massive FMH and negative KBT result. The KBT result appeared to be false-negative due to AO antagonism. However, the results of an additional marker alpha-fetoprotein (AFP) test confirmed the diagnosis of massive FMH. Therefore, measuring AFP in maternal blood can be helpful in confirming FMH in unexplained anemia of the neonate.

Should optimal timing between two intrauterine transfusions be based on estimated daily decrease of hemoglobin or on measurement of fetal middle cerebral artery peak systolic velocity?

BACKGROUND: To best predict the recurrence of fetal anemia after intrauterine transfusion (IUT), the measurement of middle cerebral artery peak systolic velocity (PSV) and the estimation of hemoglobin (Hb) daily decrease are compared. STUDY DESIGN AND METHODS: A retrospective study including 38 patients who had at least two IUTs in a context of red blood cell alloimmunization was conducted. PSV values before first, second, and third IUTs were collected and expected Hb level was calculated according to various Hb daily decrease formulas as proposed in the literature. RESULTS: Comparison of PSV receiver operating characteristic curves with the various Hb levels did not find any significant difference between first and second IUTs. On the other hand, we found a significant difference between the second and third IUTs, with better prediction of fetal anemia through Hb decrease calculation, whatever the formula. Between the second and third IUTs, no formula was significantly better than the others. CONCLUSION: The timing of a second transfusion can be difficult to determine with certainty, but PSV can give an accurate assessment of when to resample the fetus with probably a higher recommended threshold for the diagnosis of fetal anemia. Subsequent to a second transfusion, the intertransfusion interval should be based on estimated Hb decrease rather than PSV thresholds, whatever the chosen formula proposed in the literature. Larger numbers are needed to definitely make this recommendation and it will be interesting to evaluate correlation between different antibodies.

A pilot prospective study of fetomaternal hemorrhage identified by anemia in asymptomatic neonates.

OBJECTIVE: Fetomaternal hemorrhage (FMH) is a poorly understood condition in which fetal erythrocytes transfer to the maternal circulation via a faulty placental barrier. Little is known about the true incidence, epidemiology or pathophysiology of FMH in the general pregnant population as existing studies are based on retrospective cohorts and manifest diagnosis and selection bias. The objective of this study was to evaluate the practicability of a prospective study of FMH in the general population based on antepartum maternal blood testing and neonatal anemia. STUDY DESIGN: Prospective cohort study. RESULT: Nineteen pregnant women were enrolled prior to the term delivery of 20 well infants. Five neonates were unexpectedly anemic on first postnatal testing. Antenatal maternal blood samples associated with two of the five anemic newborns had positive Kleihauer-Betke testing while no newborn with a normal postnatal blood count had an associated abnormal Kleihauer-Betke test. CONCLUSION: Clinically significant FMH may be more common than previously thought. Prospective epidemiological study of FMH is feasible.

Cerebral Doppler velocimetry to predict fetal anemia after more than three intravenous fetal exchange transfusions.

BACKGROUND: We aimed to assess usefulness of the middle cerebral artery peak systolic velocity (MCA-PSV) in the prediction of fetal anemia after more than three intravenous fetal-exchange transfusions (IFET). STUDY DESIGN AND METHODS: A retrospective study was conducted over 6 years of 15 consecutive pregnancies with severe red blood cell fetomaternal alloimmunization requiring more than three IFETs. We evaluated correlation between MCA-PSV (expressed as multiples of the mean [MoM]) and pretransfusion hemoglobin (Hb) in the fetus (MoM). Analyses were also performed to assess the value of MCA-PSV to predict moderate to severe fetal anemia. RESULTS: Twenty-seven MCA-PSV measurements performed before the fourth to last IFET were coupled with pretransfusion Hb in the fetus. The median number of IFETs per fetus was five (range, four to eight). Five Hb samples found fetuses with severe (19%), seven with moderate (26%), and 15 with mild anemia (56%). There was a linear correlation between MCA-PSV(x) and Hb in the fetus(y): y = -0.21x + 0.93 (r = -0.50, p < 0.01). For the prediction of moderate to severe anemia the negative predictive value of MCA-PSV with a threshold of 1.5 MoM was 75%, positive predictive value 73%, specificity 80%, sensibility 67%, and positive likelihood ratio 3.33. The area under the receiver operating characteristic curve was 0.78 (95% confidence interval, 0.59-0.96; p < 0.001). For the prediction of severe anemia, MCA-PSV with a threshold of 1.5 MoM had 94% negative predictive value, 80% sensibility, and a positive likelihood ratio of 2.5. CONCLUSIONS: This study shows that a correlation between MCA-PSV and Hb in the fetus persists even after more than three IFETs. MCA-PSV measurements thus remain useful to monitor fetuses at risk of anemia.

Fetomaternal hemorrhage in normal vaginal delivery and in delivery by cesarean section.

BACKGROUND: The objective was to determine the incidence and volume of fetomaternal hemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these variables would enable optimalization of guidelines for D alloimmunization prophylaxis. STUDY DESIGN AND METHODS: In a prospective cohort study, a total of 3457 examinations were performed, 2413 after normal vaginal delivery and 1044 after cesarean delivery. FMH was assessed by flow cytometry. (FMH is fetal red blood cell [RBC] volume; fetal blood volume is double [expected fetal hematocrit is 50%].) RESULTS: The fetal RBC volume diagnosed in maternal circulation after delivery ranged from insignificant FMH of not more than 0.1 mL to excessive FMH of 65.9 mL (median, 0.7; mean, 0.78; SD, 1.48). FMH of more than 2.5 mL (immunoglobulin [Ig] G anti-D insufficient dose 50 µg) was observed in 1.4% (49/3457) and excessive volumes of FMH of more than 5 mL (insufficient dose, 100 µg) in 0.29% (10/3457). Delivery by cesarean section presented a higher risk of incidence of FMH of more than 2.5 mL (odds ratio, 2.2; p = 0.004) when compared with normal vaginal delivery. It did not, however, present a significant risk factor for the incidence of excessive volumes of FMH of more than 5 mL. CONCLUSION: During normal vaginal delivery as well as during delivery by cesarean section, FMH of less than 5 mL occurs in the great majority of cases, and thus for the prevention of D alloimmunization, an IgG anti-D dose of 100 µg should be sufficient. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor.

Using middle cerebral artery peak systolic velocity to time in utero transfusions in fetomaternal hemorrhage.

BACKGROUND: Fetomaternal hemorrhage is a rare cause of fetal anemia and hydrops fetalis. Early and severe fetomaternal hemorrhage may benefit from in utero transfusion(s); however, hemorrhage rate is unpredictable, and reliable criteria are needed to identify recurrent anemia. CASE: Fetal hydrops due to massive fetomaternal hemorrhage was diagnosed at 29 weeks. After the first in utero transfusion, daily monitoring of middle cerebral artery peak systolic velocity suggested recurrent fetal anemia, requiring two additional in utero transfusions at 1-week intervals. One day after the third in utero transfusion, a sudden increase in fetomaternal hemorrhage rate was suspected on a rapid elevation of middle cerebral artery peak systolic velocity, leading to immediate delivery at 32 weeks. CONCLUSION: Middle cerebral artery peak systolic velocity is a relevant, noninvasive tool for the timing of repeated in utero transfusions and of fetal delivery in case of chronic fetomaternal hemorrhage.

Fetomaternal hemorrhage.

Fetomaternal hemorrhage refers to the entry of fetal blood into the maternal circulation before or during delivery. Antenatal fetomaternal hemorrhage is a pathological condition with a wide spectrum of clinical variation. Secondary to the resultant anemia, fetomaternal hemorrhage may have devastating consequences for the fetus such as neurologic injury, stillbirth, or neonatal death. Presentation is frequently without an evident precipitating factor. Recognition may become apparent only after injury has occurred, if at all. The most common antenatal presentation is decreased fetal activity and a heightened index of suspicion is warranted in cases of persistent maternal perception of decreased fetal movements. The diagnostic standard, the Kleihauer-Betke screen, has several limitations. Management remains challenging. When detected antenatally, cordocentesis with intrauterine transfusion may be attempted to correct the anemia; however, repeat intrauterine transfusion or delivery may be necessitated to correct ongoing bleeding. Although the occurrence of large antenatal fetomaternal hemorrhage is fortunately rare, this entity likely remains underreported and underrecognized. A national registry should be created to advance our learning across institutions by reviewing the clinical presentations of fetomaternal hemorrhage, the variety of fetal heart rate tracings observed, the management strategies undertaken, and the outcomes achieved.

Sinusoidal heart rate patterns as a manifestation of massive fetomaternal hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.

OBJECTIVE: A case of fetomaternal hemorrhage (FMH) in monochorionic twins is reported. METHOD: Case report. RESULT: The patient felt a decrease in fetal movements at 32 gestational weeks. Cardiotocography showed sinusoidal heart rate patterns in both fetuses. The fetal hemoglobin level in maternal blood was 6.6% (normal 0.0-1.0%). Since the patient was diagnosed with massive FMH, cesarean section was performed and both babies delivered to receive neonatal treatment. Severe anemia was apparent in both infants, based on red blood cell count, hemoglobin concentration, and hematocrit of 86 x 10 and 85 x 10(4)/mm(3) (normal 376-456 x 10(4)/mm(3)), 3.1 g/dl each (normal 10.9-13.5 g/dl), and 10.7 and 10.4% (normal 32.2-41.2%), respectively. Severe anemia may develop in both fetuses following massive FMH in monochorionic twins. As such, if abnormal circulation is detected in 1 monochorionic twin, the other fetus will also require special attention.

[Massive fetomaternal hemorrhage--case report]. / Masywne przetoczenie plodowo-matczyne--opis przypadku.

Massive fetomaternal hemorrhage is defined as a loss of more than 30-50ml of fetal blood, transferred into maternal circulation. It can lead to severe anemization of the fetus and its consequences such as fetal hydrops or stillbirth. We present a case in which the diagnosis was based on the decresased fetal movement and pathological cardiotocography record. The Kleihauer-Betke test revealed a high percentage of fetal cells and allowed to state a proper diagnosis. An immediate cesarean section was performed and the lab tests confirmed severe anemization of the newborn.

[Evaluation of fetomaternal hemorrhage in postpartum patients with indication for administration of anti-D immunoglobulin]. / Avaliação da hemorragia feto-materna em puérperas com indicação para ministração de imunoglobulina anti-D.

This study evaluated fetomaternal hemorrhage (FMH) in 343 postpartum patients who required prophylaxis of Rh alloimmunization with anti-D immunoglobulin. The rosette test was applied to screen for patients needing quantitative determination of fetal blood transferred from the maternal circulation, which was then measured by the Kleihauer-Betke test (K-B). The rosette test was positive in 22 cases (6.4%). In five of these cases, K-B did not show fetomaternal hemorrhage (a 1.45% false-positive rate for the rosette test), and in one case the test was inconclusive. There were 8 cases with FMH < 10 ml (2.3%), 6 cases with FMH from 10 to 30 ml (1.7%), and two cases with FMH > 30 ml (0.58%), requiring a supplementary dose of anti-D. The study concludes that following the rosette test, additional evaluation of FMH using a quantitative test was unnecessary in 93.6% of the cases.

[Anaemia in two infants due to fetomaternal transfusion]. / Anemie bij 2 zuigelingen door foetomaternale transfusie.

In two neonates, a boy suffering from persistent pulmonary hypertension of the newborn and a girl with fetal distress, massive fetomaternal haemorrhage was diagnosed (290 ml). In both cases fetal monitoring showed a sinusoidal heart rate pattern and the Kleihauer-Betke test was positive. Both children were intubated and ventilated and were given an erythrocyte transfusion. They both recovered. Differentiation between acute and chronic fetomaternal haemorrhage is essential when deciding on treatment: blood transfusion in acute fetomaternal haemorrhage and exchange transfusion in chronic fetomaternal haemorrhage with normoor hypervolemia. Differentiation is difficult. Little is known about the prognosis of fetomaternal haemorrhage. Because of the nature of perinatal problems and the possibility of neurological damage, long-term follow-up is recommended.

Large fetomaternal hemorrhage: clinical presentation and outcome.

AIM: To evaluate the incidence and outcome of all neonates with demonstrated fetomaternal hemorrhages > or = 20 ml and to assess possible predictors of large fetomaternal hemorrhage and outcome. METHODS: Retrospective data analysis 1987-2000. Clinical data included antenatal events, method of delivery, condition at birth, hematology results, treatment and outcome. RESULTS: Sixteen infants were identified and treated for fetomaternal hemorrhage. Adverse outcome occurred in five infants (31%). Outcome was predicted by postnatal presentation and initial hemoglobin. CONCLUSION: Adverse outcome amongst neonates with large fetomaternal hemorrhage is high. Outcome is better predicted by initial hemoglobin than volume of hemorrhage as per the Kleihauer test.

Increased nuchal translucency and decreased fetomaternal transfusion after chorionic villus sampling.

OBJECTIVE: To investigate the relationship between nuchal translucency (NT) and fetomaternal transfusion (FMT) after chorionic villus sampling (CVS). METHODS: The level of FMT was determined in 272 viable, singleton pregnancies in which 10-14-week ultrasound scanning, NT measurement and CVS for fetal karyotyping had been performed. The pre-CVS NT was measured transvaginally, and the women were divided into two groups, i.e. those with NT < 2.5 mm (Group 1) or >or= 2.5 mm (Group 2). The level of FMT was determined via the maternal serum alpha-fetoprotein levels before and after CVS. FMT was analyzed in relation to the pre-CVS NT. RESULTS: Of the 272 pregnancies, 213 were in Group 1 and 59 in Group 2. The mean levels of FMT after CVS were 23.3 +/- 12.2 and 5.4 +/- 2.9 micro L in Groups 1 and 2, respectively (P < 0.01). An FMT > 100 micro L was found in 19 cases in Group 1, whereas the maximum in Group 2 was 67.2 micro L. Aneuploidies were diagnosed in 17 cases, 15 (88.2%) of them in Group 2. When the pregnancies with adverse outcome were excluded from the two groups, a higher level of FMT was observed in Subgroup 1 than in Subgroup 2 (P < 0.01). CONCLUSIONS: The mean level of FMT after CVS was significantly lower in pregnancies with an increased pre-CVS NT, a relationship observed in euploid pregnancies also. An increased pre-CVS NT seems to be inversely correlated with the FMT increase after CVS. Further studies are planned to investigate the background to this phenomenon.