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Rh Incompatibility in Pregnancy

 

The most common type of Rh incompatibility occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery .

 

Rh incompatibility can also occur when an Rh-negative female recei

ves an Rh-positive blood transfusion.

 

An Rh-negative woman become alloimmunized to the D antigen present on fetal red blood cells (RBCs) during the first Rh-incompatible pregnancy. The first pregnancy is rarely affected because the number of Rh antibodies produced by the mother during primary immunization is low and the antibodies are usually IgM in nature . IgM can’t cross placental barrier.

 

When the mother is exposed to D-positive fetal RBCs during a subsequent Rh-incompatible pregnancy, the mother mounts an anamnestic, or secondary, immune response to the fetus’ RBCs. A large number of IgG-class Rh antibodies are produced. The IgG antibodies cross the placenta and make fetal red cells susceptible to destruction. The fetal RBCs are then destroyed by the fetal immune system. Anemia develops in the fetus with a concomitant increase in unconjugated bilirubin. The anemia and unconjugated bilirubin levels can lead to a number of conditions.

 

Treatment with Rh IgG (RhoGAM)

 

The current recommendation is that every Rh-negative nonimmunized woman who presents to the ED with antepartum bleeding or potential fetomaternal hemorrhage should receive 300 mcg of Rh IgG IM. For every 30 mL of fetal whole blood exposed to maternal circulation, 300 mcg of Rh IgG should be administered . A lower 50-mcg dose preparation of Rh IgG is available and recommended for Rh-negative females who have termination of pregnancy in the first trimester when fetomaternal hemorrhage is believed to be minimal.

 

Because of its short half-life, Rh IgG routinely is administered once at 28-32 weeks’ gestation and again within 72 hours after birth to all Rh-negative pregnant females as a part of routine prenatal care.

 

Other important points:

 

Determination of Rh blood type is required in every pregnant female.

 Overall, 16% of Rh-negative women will become sensitized after their first pregnancy if not given Rhogam.

 In a pregnant woman with Rh-negative blood type, the Rosette screening test often is the first test performed. The Rosette test can detect alloimmunization caused by very small amounts of fetomaternal hemorrhage.

 Amniotic bilirubin scan (also known as ΔOD450) is a prenatal testing procedure . Results interpreted using a Liley or Queenan chart (Queenan chart is reported to have higher diagnostic accuracy for identifying severe anemia).

The Liley curve is divided into three zones.

 A result in Zone I indicates mild or no disease. Fetuses in zone I are usually followed with amniocentesis every 3 weeks.

 A result in zone II indicates intermediate disease. Fetuses in low Zone II are usually followed by amniocentesis every 1-2 weeks.

 A result above the middle of Zone II may require transfusion or delivery.

Obtaining maternal Rh antibody titers can be helpful for future follow-up care of pregnant females who are known to be Rh negative. Maternal serum antibody Rh titer >15 IU/mL indicates high risk of severe fetal anemia.

Immediately after the birth of any infant with an Rh-negative mother examine blood from the umbilical cord of the infant for ABO blood group and Rh type, measure hematocrit and hemoglobin levels, perform a serum bilirubin analysis, obtain a blood smear, and perform a direct Coombs test.

 A positive direct Coombs test result confirms the diagnosis of antibody-induced hemolytic anemia, which suggests the presence of ABO or Rh incompatibility.

 PRENATAL PERIOD

 • Ovum: 0 to 14 days

 • Embryo: 14 days up to 9 weeks

 • Fetus: 9 weeks to birth.

 

PERINATAL PERIOD

 • 22 weeks (stage of viability) of gestation to 7 days after birth.

 

POSTNATAL PERIOD

 TERM

 • Neonates first 4 weeks of life (28 days)

 • Early neonates till 7 days

 • Late neonates 7 to 28 days

 • LBW birth weight lower then 2.5 kg

 • Very low birth weight less then 1.5 kg

 • Extremely low birth weight less then 1 kg

 • Prematurity < 37 weeks

 • Post Maturity > 42 weeks

Fluid from Pap test used to detect ovarian, endometrial cancers

Using cervical fluid collected from routine Pap smears, U.S. researchers were able to spot genetic changes caused by both ovarian and endometrial cancers, offering promise for a new kind of screening test for these deadly cancers.


Experts say that although the test has tremendous potential, it is still years from widespread use. But if proven effective with more testing, it would fill a significant void.


Currently, there are no tests that can reliably detect either ovarian or endometrial cancer, which affects the uterine lining. Research teams have been trying for several years to find a screening test that could identify these cancers early, when there is a better chance of a cure.


"Pap smears have had a tremendous impact in reducing the rate of cervical cancer in the United States," said Dr. Andrea Myers of Dana-Farber Cancer Institute, a co-author of the commentary on the study published in Science Translational Medicine.


"The lack of an equally effective screening test for women at high risk for endometrial or ovarian cancer has created a great deal of interest in developing tests that could identify these cancers by their genetic ‘signature' - the collection of specific mutations within them," she said.


"This new study is an important step in that direction."


The new approach, developed by a team at Johns Hopkins Kimmel Cancer Center in Baltimore, piggybacks on routine Papanicolaou or Pap testing, which is already done routinely to detect cervical cancer.


The idea is to take fluid collected from the cervix for Pap tests and use gene sequencing technology to look for genetic changes that would only be found in endometrial and ovarian tumors.


Since Pap tests occasionally contain cells shed from the ovaries or the lining of the uterus, cancer cells from these organs could be present in the fluid as well.


The team tested for mutations in 24 endometrial and 22 ovarian cancers.


'EXCITING FIRST STEP'


"We could detect 100 percent of endometrial cancers and 40 percent of ovarian cancers, even at the earliest stages of their disease, and we can do it without any false positives," said Dr. Luis Diaz, associate professor of oncology at Johns Hopkins, who worked on the study published on Wednesday in Science Translational Medicine.


Diaz called the study "an exciting first step."


"We're seeing high sensitivity in endometrial cancer. We're seeing moderate sensitivity in ovarian cancer, and we're seeing no false positives," he said.


That offered enough rationale to start tests on 100 ovarian cancers of different stages and 100 endometrial cancers, as well as a large number of samples from healthy women.


The team hopes to complete that testing by the end of the year.


Dr. Shannon Westin, an expert in gynecologic cancers at the University of Texas MD Anderson Cancer Center, said the need for a screening test for these two cancers is great.


In the United States, the two cancers combined are diagnosed in 70,000 women each year, and about 23,500 women will die from these cancers.


Westin, who co-wrote a commentary on the study, said the paper is "very compelling and very interesting" that you could find evidence of these cancers in a screening test using fluid from Pap tests.


But the test must still be validated and shown to be effective in a large populations of women, a process that could take 10 to 15 years.


"It's a great first step. It is a proof of principle that this can be done. Patients are used to getting the Pap smear. They understand it," she said. That might mean women would ultimately be comfortable getting this type of test.


Dr. David Chelmow, a professor of obstetrics and gynecology at Virginia Commonwealth University Medical Center, who was not involved with the research, said it would be "fantastic" to have a test that would reliably detect cancers.


"It's an innovative idea. It's neat. But the question is really going to be what happens when this gets more thoroughly tested," he said.


Diaz said currently there are no tests to screen for these cancers early. The experimental test would cost about $100, but with the falling cost of sequencing technology, he estimates it will be half or even a tenth of that cost within the next year.


 

 What is Perinatal Asphyxia?

 

Perinatal asphyxia, or birth asphyxia, results from an inadequate intake of oxygen by the baby during the birth process - before, during, or just after birth. Decreased oxygen intake can result in chemical changes in the baby's body that include hypoxemia, or low levels of oxygen in the blood, and acidosis, in which too much acid builds up in the blood.

Symptoms

 

Symptoms of birth asphyxia may not be obvious, but the most common symptoms include:

Before birth, abnormal fetal heart rate and low pH levels, indicating too much acid

At birth, poor skin color, low heart rate, weak muscle tone, gasping or weak breathing, and meconium stained amniotic fluid

Cervical fluid of patients with gynecologic cancer carries normal cellular DNA mixed together with DNA from cancer cells, according to the investigators. Their task was to use genomic sequencing to distinguish cancerous from normal DNA.

The scientists had to determine the most common genetic changes in ovarian and endometrial cancers to prioritize which genomic regions to include in their test. They searched publicly-available genome-wide studies of ovarian cancer, including those done by other Johns Hopkins investigators, to find ovarian-cancer specific mutations. Such genome-wide studies were not available for the most common type of endometrial cancer, so they conducted genome-wide sequencing studies on 22 such cancers.

From the ovarian and endometrial cancer genome data, the researchers identified 12 of the most frequently mutated genes in both cancers and developed the PapGene test with this insight in mind.

The investigators then applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital in Baltimore, Memorial Sloan-Kettering Cancer Center in New York City, the University of Sao Paulo in Brazil and ILSBio, a tissue bank. The new test detected both early- and late-stage disease in the endometrial and ovarian cancers tested. No healthy women in the control group were misclassified as having cancer.

The investigators’ next steps include applying PapGene on more samples and working to increase the test’s sensitivity in detecting ovarian cancer. "Performing the test at different times during the menstrual cycle, inserting the cervical brush deeper into the cervical canal and assessing more regions of the genome may boost the sensitivity," said Chetan Bettegowda, MD, PhD, assistant professor of neurosurgery at Johns Hopkins.

Together, ovarian and endometrial cancers are diagnosed in nearly 70,000 women in the United States each year, and about a third will die from their disease.

Info: Non-stress Test

 

The Fetal Non-Stress test is a simple, non-invasive test performed in pregnancies over 28 weeks gestation. The test is named “non-stress” because no stress is placed on the fetus during the test

 At term fetus weighs around 6-7times the placental weight. A relative heavy or light placenta often indicates an abnormal pregnancy.

 

Large placentae are seen in Rh incompatibility, chronic intrauterine infections and maternal diabetes.

 

Small placentae are seen in toxemia of pregnancy, hypertension, multiple congenital anomalies, intrauterine growth retardation and severe diabetes.