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  1. Define hemolytic disease of the newborn (HDN) and explain how it is diagnosed.

  2. Define gestational diabetes mellitus (GDM) and its consequences for the mother and fetus.

  3. Explain how ACOG recommends that GDM be diagnosed and discuss the different criteria for screening and diagnosing GDM.

  4. Describe the screening methods for fetal aneuploidies during the first and second trimesters.

  5. Define the role of cell-free fetal DNA testing in screening for fetal aneuploidies.

  6. List the changes in thyroid function tests during pregnancy.

  7. Summarize the utility of acid-base and blood gas measurements in umbilical cord blood.

  8. Discuss fetal lung maturity testing and the available methods.


Normal physiological changes during pregnancy are reflected in both fetal and maternal hematologic and biochemical parameters. These normal changes can make the diagnosis of disease during pregnancy difficult. This chapter is intended to review the recent clinical and laboratory updates in maternal-fetal screening and diagnosis of hemolytic disease of the newborn (HDN), gestational diabetes mellitus (GDM), fetal aneuploidies, thyroid disease, and other related topics.


Hemolytic disease of the newborn (HDN) is a hemolytic disorder characterized by the destruction of fetal red blood cells by maternal antibodies. These antibodies appear in the maternal circulation due to blood group incompatibility between the mother and fetus, such as when an Rh(D) negative mother is pregnant with an Rh(D) positive fetus.1 Other terms used to describe this condition include isoimmunization disease, Rh isoimmune disease, Rh disease, or D isoimmunization. As this process involves the production of antibodies in one individual (mother) and cell destruction in another (fetus), in vivo HDN is considered the most complex of the three common forms of IgG-mediated red blood cell destruction, that is, HDN, autoimmune hemolytic anemia, and hemolytic transfusion reactions.

The production of maternal antibodies against fetal red blood cell antigens is called sensitization, and it often occurs in a pregnancy in which the fetus' blood cell antigens are foreign to the mother.2,3 It is widely assumed that fetal and maternal blood compartments are separate during pregnancy; nevertheless, a few fetal red blood cells manage to enter the maternal circulation continuously. This seemingly harmless antigenic challenge is adequate to provoke an antibody response in some women. Significantly larger antigenic loads may occur with any fetomaternal hemorrhage, such as that seen in (1) spontaneous or induced abortions, (2) ectopic pregnancies, or (3) delivery of an infant.4 Naturally, the larger the fetomaternal hemorrhage, the higher the possibility that the mother will respond by producing more antibodies. Alloimmunization usually affects the fetus of the second pregnancy because the exposure to these antibodies typically occurs late during pregnancy or at delivery; thus, the fetus of the first pregnancy is rarely affected.

Maternal IgG antibodies can be actively transported across the placental to the ...

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