SMFM clinical guidelineSociety for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: The fetus at risk for anemia–diagnosis and management
Section snippets
What is the definition of fetal anemia?
Fetal anemia can be defined using either hemoglobin or hematocrit values. A hemoglobin value that is more than 2 SD below the mean is diagnostic of fetal anemia. Normally, fetal hemoglobin concentration increases with advancing gestation (Figure 1).1 Reference ranges for fetal hemoglobin concentrations as a function of gestational age (from 18 to 40 weeks of gestation) have been established using fetal blood sampling (Table 1).1
The severity of fetal anemia can be categorized based on hemoglobin
What are the causes of fetal anemia?
Fetal anemia can result from a large number of pathologic processes (Table 2). The most common causes in the United States are maternal alloimmunization and parvovirus infection. Other causes include inherited conditions such as alpha-thalassemia and genetic metabolic disorders as well as acquired conditions, such as fetal blood loss and infection. Fetal anemia can occur in association with Down syndrome, because of transient abnormal myelopoeisis, a leukemic condition that occurs in
What is the appropriate management for the patient at risk for fetal anemia?
Women with pregnancies with the conditions listed in Table 2, most commonly red blood cell alloimmunization and parvovirus infection, are considered at risk for fetal anemia. The management of such patients is based on the suspected etiology. In women with red cell alloimmunization, parental assessment and testing are key initial steps to determine the potential fetal antigen status (Figure 2). This can be done through parental zygosity testing, direct genotyping of the fetus with
How is the diagnosis of fetal anemia made?
An algorithm for the screening and diagnosis of fetal anemia is presented in Figure 2. The definitive diagnosis of fetal anemia is generally made by fetal blood sampling, whereas screening is performed with MCA Doppler.
What are optimal techniques for performing a measurement of the MCA-PSV?
Operators should be trained to measure the MCA-PSV using the proper technique.51 A step-by-step video tutorial is available at SMFM.org/AJOG.org (Video). The steps for correct measurement of the MCA-PSV are the following:
- 1.
Obtain an axial section of the fetal head at the level of the sphenoid bones during a period of fetal rest.
- 2.
Image the circle of Willis with color Doppler.
- 3.
Select the area of the MCA close to the transducer.
- 4.
The entire length of the MCA should be visualized.
- 5.
Zoom the area of the
After anemia is detected, what is the management?
An algorithm for the diagnosis of fetal anemia in the pregnancy complicated by red cell alloimmunization is depicted in Figure 2.
If the fetus is deemed at a significant risk for severe anemia based on the MCA Doppler, fetal blood sampling should be offered after counseling the parents.35 It is important to have a coordinated team effort among individuals familiar with fetal blood sampling and intrauterine fetal transfusion. Referral to a center with expertise in invasive fetal therapy is
What is the appropriate timing of delivery for the fetus at risk for anemia?
Unfortunately, there are no high-quality data regarding the optimal timing of delivery in the fetus at risk for anemia or in the fetus receiving in utero therapy because of anemia. Expert opinion suggests planning delivery at 37–38 weeks of gestation based on balancing the risk of stillbirth, the consequences of fetal anemia, and the risks of another fetal blood sampling procedure/intrauterine transfusion, against the risks of prematurity and the additional morbidity of anemia and
Short-term neonatal outcomes after treatment
With the use of intrauterine transfusions (IUTs), overall perinatal mortality in severe fetal anemia has decreased to less than 10%. Postnatal management of hemolytic disease of the newborn is primarily centered on the treatment of hyperbilirubinemia with phototherapy and exchange transfusions to prevent kernicterus. Other short-term complications include neonatal anemia, thrombocytopenia, cholestasis, and respiratory disease. Neonates who have undergone multiple intrauterine transfusions are
Maternal
The mainstay of treatment for severe fetal anemia is intrauterine blood transfusion. Unfortunately, this therapy is associated with a risk of immunization to additional antigens, despite the relatively small amount of blood transfused. In one large cohort, 25% of women formed additional antibodies after IUT, and more than 70% had multiple red blood cell antibodies postpartum.61 The risk is highest when the IUT requires transplacental passage of the needle. The presence of multiple antibodies
Acknowledgment
We recognize and thank Dr Ken Moise for his editorial review and input into the document.
References (78)
- et al.
Fetal haemoglobin measurement in the assessment of red cell isoimmunisation (Level II-3)
Lancet
(1988) - et al.
Incidence of parvovirus B19 infection among an unselected population of pregnant women in The Netherlands: a prospective study (Level II-1)
Eur J Obstet Gynecol Reprod Biol
(2006) - et al.
Management and outcomes of pregnancies complicated by human B19 parvovirus infection: a prospective study (Level II-2)
Am J Obstet Gynecol
(1990) - et al.
Toxoplasmosis, parvovirus, and cytomegalovirus in pregnancy (Level III)
Clin Lab Med
(2010) - et al.
Fetomaternal haemorrhage discovered after trauma and treated by fetal intravascular transfusion (Level III)
Eur J Obstet Gynecol Reprod Biol
(1997) - et al.
clinical guideling #7: non-immune hydrops fetalis (Level III)
Am J Obstet Gynecol
(2015) - et al.
Fetal blood sampling (Level III)
Am J Obstet Gynecol
(2013) - et al.
Have Liley charts outlived their usefulness (Level II-3)?
Am J Obstet Gynecol
(1986) - et al.
Does midtrimester delta OD450 of amniotic fluid reflect severity of Rh disease (Level II-3)?
Am J Obstet Gynecol
(1989) - et al.
Midtrimester amniotic fluid delta optical density at 450 nm in normal pregnancies (Level III)
Am J Obstet Gynecol
(1986)
Accurate prediction of fetal hemoglobin by Doppler ultrasonography (Level III)
Obstet Gynecol
Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome (Level II-2)
Am J Obstet Gynecol
Angle correction can be used to measure peak systolic velocity in the fetal middle cerebral artery (Level III)
Am J Obstet Gynecol
Porencephalic cyst: a complication of fetal intravascular transfusion (Level III)
Am J Obstet Gynecol
Changes in hemorheology with fetal intravascular transfusion (Level II-2)
Am J Obstet Gynecol
Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization (Level II-3)
Am J Obstet Gynecol
Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study (Level II-2)
Am J Obstet Gynecol
Intrauterine transfusion for parvovirus B19 infection: long-term neurodevelopmental outcome (Level II-2)
Am J Obstet Gynecol
Neurodevelopmental outcome after intrauterine red cell transfusion for parvovirus B19-induced fetal hydrops (Level II-2)
BJOG
Observational study of effect of intrauterine transfusions on outcome of fetal hydrops after parvovirus B19 infection (Level II-3)
Lancet
Fetal anemia due to non-Rhesus-D red-cell alloimmunization (Level III)
Semin Fetal Neonatal Med
Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism (Level II-2)
Pediatrics
Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease (Level II-3)
Am J Obstet Gynecol
Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6 years (Level II-2)
Obstet Gynecol
Long-term neurodevelopmental outcome and brain volume after treatment for hydrops fetalis by in utero intravascular transfusion (Level II-2)
Am J Obstet Gynecol
Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses (Level II-1)
N Engl J Med
Management of rhesus alloimmunization in pregnancy (Level III)
Obstet Gynecol
Fetal hydrops and hepatosplenomegaly in the second half of pregnancy: a sign of myeloproliferative disorder in fetuses with trisomy 21 (Level III)
Ultrasound Obstet Gynecol
Trisomy 21, fetal hydrops, and anemia: prenatal diagnosis of transient myeloproliferative disorder (Level III)?
Obstet Gynecol
Management and outcome in prenatally diagnosed sacrococcygeal teratomas (Level III)
Pediatr Int
Diffuse neonatal haemangiomatosis with intra-uterine haemorrhage and hydrops fetalis: a case report (Level III)
Eur J Pediatr
Society of Obstetricians and Gynaecologists of Canada. Parvovirus B19 infection in pregnancy (Level III)
Obstet Gynaecol Can
Immediate and long term outcome of human parvovirus B19 infection in pregnancy (Level II-2)
Br J Obstet Gynaecol
Risks associated with human parvovirus B19 infection (Level III)
MMWR Morb Mortal Wkly Rep
Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy (Level II-2)
Singapore Med J
TAPS and TOPS: two distinct forms of feto-fetal transfusion in monochorionic twins (Level III)
Z Geburtshilfe Neonatol
Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence (Level II-2)
Obstet Gynecol
Fetal intraperitoneal transfusion for iatrogenic twin anemia-polycythemia sequence after laser therapy (Level III)
Ultrasound Obstet Gynecol
Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, and clinical effects (Level III)
Transfusion
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