During normal pregnancy, the female body undergoes physiologic changes in almost every organ system to harbor the growing fetoplacental unit. The hematologic system is no exception to this convention as the maternal blood undergoes changes both in quantity as well as its constitution. The constituents of maternal blood are testable to screen and diagnose a wide variety of conditions relating to both healthy pregnancies as well as diseases associated with pregnancy.
A little before reaching full term, the volume of maternal blood is about 30% above baseline. The excess is likely due to increased levels of estrogen and aldosterone, which cause the kidneys to retain higher amounts of fluid. A higher number of erythrocytes accompanies this excess fluid with a slightly increased mean corpuscular volume in a healthy pregnancy.[1] Therefore, at delivery, there are between 1 to 2 liters of excess blood in the maternal circulatory system.
The prominent hematologic changes are physiologic anemia, expanded plasma volume, mild thrombocytopenia, a mild prothrombotic state, and in some individuals, mild neutrophilia. Other than the above changes, maternal blood also contains a wide number of other antigens, proteins, and hormones of clinical significance.
Certain findings fall outside the parameters of a normal physiologic pregnancy and require additional evaluation.
Maternal blood acts as the medium, which enables provision to the developing fetus of nutrients, gaseous exchange, and waste disposal. The placenta here serves as the gatekeeper of this exchange. Maternal blood floods the intervillous spaces, which is where the transfer takes place via both active and passive transport. Carbon dioxide, urea, uric acid, and creatinine are disposed into the maternal blood from the fetal circulation. Maternal blood contains IgG antibodies which diffuse through the placenta and provide naturally acquired passive immunity to the infant during the crucial first few months of life.
Initial Prenatal Screen
Prenatal care should be established in all women, ideally by ten weeks of pregnancy. Although the initial prenatal visit includes a history, physical examination, imaging studies, and blood work, in this section, we will only discuss the components of the prenatal evaluation that pertain to the maternal blood.
The tests commonly advocated in all patients are as follows:
For special at-risk patients, the following tests may be undertaken:
Serum Human Chorionic Gonadotropin
Human chorionic gonadotropin (hCG) is a hormone produced by the syncytiotrophoblast cells of the placenta after implantation. The primary function of hCG is to maintain the corpus luteum and thus progesterone secretion for the first 8 to 10 weeks of pregnancy, after which the placenta takes over the function of hormone production, and the corpus luteum degenerates. The hCG serves as an important biomarker for the detection of pregnancy, disease states associated with pregnancy, diagnosis of aneuploidies as well as a tumor marker for gestational trophoblastic disease, and germ cell tumors. The detection of the beta subunit hCG serves as the basis of the pregnancy test.
Types of hCG assay:
Conditions with increased levels of hCG
Conditions with decreased levels of hCG
Anemia in Pregnancy
About 30 percent of women in the reproductive age group are anemic [6]. The World Health Organization (WHO) estimates that within the reproductive age group, the prevalence of anemia in pregnant women is even higher at around 40 percent. Given this high prevalence, recommendations for screening for anemia are at the first prenatal visit, with a repeat between 24 and 28 weeks of pregnancy.
As per the American College of Obstetricians and Gynecologists (ACOG) and the World Health Organization (WHO), anemia in pregnancy is defined as [7][8][9]:
Several causes lead to anemia in pregnancy, but chief among them are physiologic (dilutional) anemia of pregnancy and iron deficiency anemia.
Gestational Diabetes
Gestational diabetes has historically been defined as abnormal glucose tolerance with first onset or recognition during pregnancy [10]. Within the United States, the prevalence of gestational diabetes mellitus is roughly 6 percent [11]. Human placental lactogen secreted by the syncytiotrophoblasts of the placenta increases the overall insulin resistance. Since uncontrolled maternal blood glucose levels can result in several adverse outcomes for the mother and fetus, it is necessary to screen and treat gestational diabetes.
The most common method is 2-step testing:
A glucose concentration greater or equal to these values at two or more points is considered a positive test.
RhD Alloimmunization in Pregnancy
When Rh-D negative women deliver an Rh-D positive baby or have any mixing of Rh-D positive blood, the maternal immune system develops an antibody response to the Rh-D antigen. During any subsequent pregnancy, an Rh-D positive fetus or neonate is at risk of suffering from the hemolytic disease of the newborn due to the maternal immune system attacking the fetal red blood cells owing to the prior activation against this antigen. Due to the morbidity and mortality associated with this preventable condition, Rhesus typing and an antibody screen should be performed at the initial prenatal visit and then again at 28 weeks. The standard methods of screening maternal blood include:
The Kleihauer–Betke is a special test performed on maternal blood used to calculate the required dosage of Rh-D immune globulin to inhibit the formation of Rh antibodies in the mother and prevent Rh disease in the future Rh-positive children. It measures the quantity of fetal hemoglobin transferred into the maternal blood and, based on that, gives an estimate of the dose of Rh-D immune globulin required.
Cell-free DNA (cfDNA) Testing
CfDNA is produced by the mother as well as the feto-placental unit. There are two sources of fetal cfDNA in maternal plasma. It can be either from the apoptosis of the syncytiotrophoblasts (placental cells) or the apoptosis of fetal erythroblasts, which generate cfDNA in fetal circulation, after which the fragments cross the placenta into the maternal circulation. These fragments of feto-placental cfDNA can be extracted from maternal blood and analyzed for abnormalities. Fetal cfDNA first appears in maternal blood at five weeks of gestation and is always present at around nine weeks of gestation[12]
Indications:
Applications:
1. Trisomies: cfDNA has the highest sensitivity for detecting aneuploidies such as trisomy 21, 18, and 13. The detection rate (DR) for the aneuploidies is as follows [13][14][15][16]:
2. Sex chromosome aneuploidies: Although based on the same principle, the cfDNA can help to detect sex chromosome aneuploidies, the DR is much lower than for the common autosomal aneuploidies.
3. Fetal sex determination
Maternal Serum Alpha-fetoprotein (MSAFP)
Alpha-fetoprotein is a globulin synthesized in the fetal yolk sac, liver as well as gastrointestinal tract. Although its function is unclear, it may play a role in immunoregulation and act as an intravascular transport protein. AFP is secreted into the fetal urine by the kidneys and then excreted into the amniotic fluid. From here, it finds its way into maternal serum, and this maternal serum alpha-fetoprotein can be measured to screen and diagnose certain conditions. MSAFP is measured at 15 to 20 weeks of gestation (optimally at 16 to 18 weeks) to screen for fetal anomalies.
Increase MSAFP levels:
Decreased MSAFP levels:
Liver Disorders of Pregnancy
There are a few disorders of the hepatobiliary system that are unique to pregnancy and are diagnosable with blood work.
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