Non-Invasive Protocol For The Screening, Diagnosis and Treatment Of Hemolytic Perinatal
Authors: Rodriguez Nancy , Noguerol Pilar , García Lutgardo , Macher Hada , Carmona Magdalena , Martín Jesús , Pérez Simon Jose Antonio 
Published: October 2019

Abstract
A protocol-based and multidisciplinary follow-up of the pregnant woman including Primary Care, Hematology Deparment, and Fetal Medicine, is required for the appropriate prophylaxis and treatment of the hemolytic disease of the newborn (HDN). The combined application of new monitoring techniques, such as the study of the fetal D antigen (RhD) by PCR in maternal blood and the determination of the blood flow of the middle cerebral artery (MCA) in the fetus by Doppler ultrasonography allows the child’s prenatal follow up without invasive procedures.

Objectives
To evaluate the results obtained using this strategy of combined monitorization in our institution from 2009. Secondary aims were:
To review all cases of immunized pregnant women and to analyze the outcomes of selective anti D prophylaxis at week 28, according to fetal RHD analyzed by PCR in maternal blood.
Patients and Method s
38,000 pregnant women are included in the analysis. Antibody (Ab) screening is made during the first 3 months of pregnancy, and titer is evaluated using agglutination tests in immunized women with clinically significant (CS) Ab. RhD negative women immunized against RhD undergo fetal RHD and SRY determination using a new multiplex RT-PCR assay for fetal cell-free DNA in maternal plasma as soon as possible.
In addition, in patients with CS-Ab and previous obstetric complications or antibody titer >1/32 or rising, MCA Doppler is performed to assess the degree of fetal anemia and evaluate the need for intrauterine transfusion (IUT), or to advance childbirth to week 34.
On the other hand, non-immunized RhD negative, women are controlled again in the 28th week to re-assess the presence of antibodies and well as fetal RHD and SRY determination and only those with RHD positive fetuses receive anti D gammaglobulin.

Results
Ab were found in 290 pregnant women. 116 were not clinically significant and did not require further control. 174 women had CS-Ab against Rh, Kell, Jk, Fy, and Lu antigen systems.
Out of them, 29 RhD negative women were immunized against anti D (all of them due to previous incomplete or no prophylaxis). The study of fetal RHD revealed that 9 of these 29 women had RHD- fetuses and were released from hospital. The remaining 20 RhD- patients together with those 145 women with other CS-Ab underwent obstetric history assessment as wellas antibody titers assay, and MCA Doppler, according to the criteria mentioned above. Remarkably, after these assessments only 11 IUTs were required in 6 pregnant women, all of them were performed without any complications. Involved antibodies in these 6 patients were: Rh, Kell and Jk.
Fetal RHD testing in 4,064 RhD negative women at the 28thweek detected 1,423 who had RHD- fetuses which did not require prophylaxis. There were no false negatives among the newborns.

Conclusions
1. A combined monitorization strategy of the pregnant woman avoids unnecessary controls and invasive procedures.
2. Anti D prophylaxis has 100% efficacy in all pregnant women requiring it.
3. Those women immunized against RhD, who had RHD- fetuses, can have a quiet gestation since week 12 without further immunohematologic assessments.

Disclosures:
No relevant conflicts of interest to declare.