SMFM clinical guideline
Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: The fetus at risk for anemia–diagnosis and management

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Objective

We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia.

Methods

A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence.

Results and Recommendations

We recommend the following: (1) middle cerebral artery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluid delta OD450 not be used to diagnosis fetal anemia; (3) MCA-PSV assessment be reserved for those patients who are at risk of having an anemic fetus (proper technique for MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus is deemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing the second procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.

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.

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