Pregnancy: Preconception

There are hundreds of diseases that are related to changes in our genetic code, but most of them are extremely rare. Mutations or alterations in specific genes may prevent the genes from creating vital proteins or cause alterations in the proteins that they produce. These changes can affect the way that the body functions and cause specific diseases. Some of the disease-related gene mutations are recessive, while others are dominant. Some are X-linked or sex-linked, associated with the X or Y chromosome that determines our sex, and are found only in males. Some mutations have arisen and been passed down in specific families, and some are more prevalent in individuals of certain ethnic descent.

Genetic testing is a personal choice. Blood tests for some of the more common genetic diseases may be performed on a woman and her partner before a pregnancy if they wish to know if they are carriers. Many times, genetic testing is done first on the woman and only done on the partner if the woman is a carrier. Couples should talk to a genetic counselor about their ethnicity and family medical history to determine which tests are the most appropriate and to help them make an informed decision. For more information on genetics and genetic testing, see The Universe of Genetic Testing.

Individuals of Ashkinazi (East European) Jewish descent, for example, are at increased risk of carrying the genes for Tay-Sachs, Gaucher, Canavan disease, and familial dysautonomia. These genetic diseases can occur when both parents have an abnormal gene and their child inherits two copies of the abnormal gene, one from each parent. In both Tay-Sachs and Canavan diseases, there is a buildup of a substance in the child’s brain that prevents normal development. There is no known cure for either disease. Children with Tay-Sachs rarely live past five years of age; children with Canavan disease may live to early adolescence. There are three types of Gaucher disease, each causing too much fatty substance to be stored in the bone marrow, spleen, and liver. Although one type of Gaucher disease is fatal, the most common type is not. Treatments are available for individuals with Gaucher disease. Familial dysautonomia is caused by incomplete development of nerve fibers in the autonomic and sensory nervous systems. There are a variety of symptoms (which range in severity), the most noticeable of which is the lack of tears during crying.

The following are tests that may be offered to the woman and her partner to evaluate the risk of inherited diseases.

Hemoglobin is a protein that binds and releases oxygen. Found in all red blood cells (RBCs), hemoglobin transports oxygen throughout the body and releases it to the cells and tissues. Each person inherits from their parents the genes that produce hemoglobin. Some individuals inherit abnormal genes that can cause hemoglobin disorders. In diseases called thalassemias, not enough normal hemoglobin is produced to supply the body with sufficient oxygen. Inheriting one or more thalassemia genes from one or both parents can cause mild to severe anemia and the production of smaller RBCs.

In diseases called hemoglobinopathies, the hemoglobin genes make abnormal hemoglobin that may not function like normal hemoglobin. It usually takes two abnormal genes, one from each parent, to cause disease. The best known example is sickle cell disease, a serious hemoglobinopathy that causes anemia, susceptibility to infection, and organ damage in affected infants. Carriers of the sickle cell disease (those who have inherited only one sickle hemoglobin gene) do not get the disease but can pass their abnormal gene on to their children. If a carrier of the disease has a child with another carrier, their child is at risk of inheriting the sickle cell gene from each parent and having the disease.

If a woman or her partner has a strong family history of thalassemia or hemoglobinopathy or is of an ethnicity that has an increased prevalence of one of the diseases, she and her partner may want to talk to a genetic counselor about genetic testing before the pregnancy. For example, sickle cell disease is most common in people of African heritage. Thalassemias are most common in people of Mediterranean, African, or Asian descent.

Even when there is no family history of the disorder, the American College of Obstetricians and Gynecologists (ACOG) recommends that all couples planning a pregnancy or having their first visit for prenatal care be offered a carrier screening test for cystic fibrosis (CF). CF testing is now also recommended for all newborns, and all states include a CF test in their newborn screening panel [See Newborn Screening for more information]. Laboratories use CF gene mutation testing to check for 23 or more common CF gene mutations. Those who have an identified CF gene mutation in their family should be tested specifically for that mutation.

CF is a relatively common recessive genetic disorder that is caused by a mutation in a particular gene. If a person receives an altered gene from one parent and a normal gene from the other parent, he or she will be a CF carrier. Carriers do not have symptoms and are not ill, but they may pass their abnormal copy of the gene on to their children. About 1,000 different CF gene mutations have been identified, but only a few are common. Caucasians from Northern Europe and Ashkenazi Jews have the highest population carrier rates (about 1 in 20 to 25).

If both parents are carriers and both pass the altered genes on to their child (a possibility that is fairly uncommon), then that child will have CF. Those with the disorder have thick, sticky mucus in their lungs and pancreas. This can lead to frequent respiratory infections, obstructed pancreatic and liver ducts, and impaired protein digestion. The majority of males with CF are also infertile due to missing or underdeveloped vas deferens, the tubules that transport sperm from the testes. Most people with CF develop respiratory and pancreatic symptoms very early, although symptom severity varies from person to person, even in those with the exact same mutation.

Couples planning a pregnancy can talk to their healthcare provider and a genetic counselor about this test and other genetic testing. A genetic counselor can provide additional information and help to make an educated decision about the risk of having a child born with CF. If both parents are carriers, the pregnant woman can have amniocentesis or chorionic villus sampling to help diagnose or rule out CF in the fetus.

Rubella is caused by a virus that is passed from person to person by coughs or sneezes. Any contact with the nasal or throat secretions of an infected person can spread the virus. Women who have either had a rubella infection or have received the vaccination will have an antibody in their blood that will usually prevent them from getting the infection a second time. This antibody also protects the unborn baby against the virus; this protection is called immunity.

Rubella infections during childhood usually cause mild symptoms. However, if a woman becomes infected with rubella during the first 3 months of her pregnancy and does not have immunity to the virus, the baby is at risk of having serious birth defects.

All women considering a first-time pregnancy or those who are pregnant for the first time should be tested to see if they have this immunity. A blood specimen is tested to see if a sufficient amount of antibody is present in the blood to protect the pregnant woman and the fetus. If a woman does not have enough antibodies and is not currently pregnant, she may be given a rubella vaccination. She should then wait at least 28 days before becoming pregnant.

The rubella vaccine is a weakened form of a live virus and should not be given to a woman who is currently pregnant. If a pregnant woman does not have sufficient antibody to protect her and her baby, she will be advised by her healthcare practitioner to avoid contact with anyone who has symptoms of rubella throughout the rest of her pregnancy. She should consult with her healthcare provider about the best time to get vaccinated after her baby is born and follow through with getting a rubella vaccination so that her next baby will be protected.

Testing for human immunodeficiency virus (HIV) infection has become routine prenatal care in the United States. Some states even require that all pregnant women and/or their newborns be tested. Treatment begun during pregnancy can prevent the disease in the child and improve the mother's health as well. Even so, not all women receive routine prenatal care or are offered the test during pregnancy, acknowledges the U.S. Centers for Disease Control and Prevention (CDC), and some women do not agree to have the test. Ideally, the woman will have the blood test as part of her pre-conception care or early in the pregnancy. This best protects the mother and baby.

• Screening the mother: All pregnant women in the United States should be counseled about HIV early in their pregnancy and receive voluntary HIV testing to protect the child’s health. This is the recommendation of many groups, including the U.S. Public Health Service, American Academy of Pediatrics, American College of Obstetricians and Gynecologists, and U.S. Preventive Services Task Force. Repeating the test in the third trimester is of value to those at high risk for HIV infection.
• Screening the baby: In the United States, if the mother’s HIV status is not determined before or during pregnancy or during labor and delivery, healthcare practitioners recommend that the newborn be given an HIV test within 24 hours of the birth (in a few states, this is a requirement; see Newborn Screening). Treatment begun within 48 hours of birth helps prevent a baby who was exposed to the virus from becoming infected.

HIV is the virus that causes AIDS (acquired immunodeficiency syndrome). If a pregnant woman is infected with HIV, the virus can be passed to and infect her baby.

The screening tests detect HIV antigen (p24) and/or HIV antibodies in the blood. The combination HIV antibody and antigen test is the recommended screening test for HIV. It is available only as a blood test. By detecting both antibody and antigen, the combination test increases the likelihood that an infection is detected soon after exposure. Some screening tests detect only HIV antibody. These tests are available as blood tests or tests of oral fluid.

If the screening test is positive, it must be followed by a second antibody test that is different than the first test. If the second test does not agree with the first test, then a third test is performed that detects the genetic material (RNA) of the virus.

If a woman's confirmatory tests indicate an HIV infection, she will want to consult with her healthcare provider before becoming pregnant about the risks of infecting a baby and the effects of the pregnancy on her health. Treatment of HIV-infected mothers during pregnancy, precautions at birth, and avoiding breast-feeding can minimize the risk of passing the infection from mother to child. Giving the antiretroviral drug zidovudine intravenously during labor and delivery and also to the newborn twice a day by mouth for 6 weeks reduces the rate of transmission from 25-33% to about 1-2%. A combination of antiretroviral therapies is most effective at reducing the risk of HIV transmission to the baby.

A negative test for the antibody to HIV may mean that there is no infection or that a sufficient amount of the antibody has not yet been produced to be detected. If a woman participates in high-risk activities that may transmit HIV, such as unprotected sexual contact or intravenous drug use, she should be retested one or more additional times during the pregnancy.

Gonorrhea, chlamydia, and syphilis are three common sexually transmitted diseases (STDs) caused by bacterial infections. In a pregnant woman, these diseases can lead to a miscarriage or infect the baby before or during delivery. The baby may then have serious health issues such as infections of the eye, joints, or blood; blindness; or breathing problems. Some of these problems are life-threatening. The woman's health is also endangered by an STD. The best approach is for the woman to receive antibiotics to cure the bacterial infection before the pregnancy or before delivery.

All women in the United States should be tested for these STDs before planning a pregnancy and early in their prenatal care, such as during their first prenatal visit. If a woman is younger than 25 years old, engages in high-risk activities during her pregnancy such as unprotected sexual contact, or is otherwise at risk, retesting for STDs later in the pregnancy is advised.

Chlamydia and gonorrhea tests detect the presence of bacteria in the sample. Some tests use a urine sample or cervical swab. If the test is positive, the person has a current STD infection that requires treatment.

The syphilis test is a blood test. It detects an antibody produced by the body in response to the infection. The test does not distinguish between a current or past infection and, if it is positive, confirmatory testing will be required. A negative test result usually means that the woman is not currently infected; however, it is possible that an infection is too new to detect. Some states require all women to be screened for syphilis during delivery.

Many women and men do not know when they have an STD, and some healthcare practitioners do not routinely screen for STDs, the U.S. Centers for Disease Control and Prevention (CDC) acknowledges. Tests for some STDs should be offered routinely during prenatal care because early treatment lowers the chance that the baby also will contract the disease. Other STDS of concern during pregnancy are trichomoniasis, herpes, hepatitis B and hepatitis C and human immunodeficiency virus (HIV). Screening for each of these should also be part of the first prenatal visit as early in the pregnancy as possible, say the 2010 guidelines published by the CDC.

Be sure to ask when planning a pregnancy, at an early prenatal visit, and again in the third trimester about the STD tests appropriate for you and your sexual partner at that time.

A Pap test is used to screen a woman's cervix (the opening to the uterus) for cancer, pre-cancerous changes, inflammation, and some sexually transmitted diseases. HPV testing detects the high-risk types of the human papillomavirus, which increase a woman's risk of cervical cancer. Several health professional organizations recommend the following:

• Screening with Pap tests should begin no earlier than age 21.
• Women between the ages of 21 and 30 should have a Pap test every 3 years.
• Women between the ages of 30 and 65 should have both a Pap test and an HPV test every 5 years (preferable); a Pap test alone every 3 years is also acceptable.

In most cases, if a woman has a negative HPV test and/or normal Pap test within the recommended interval, she will not require the tests when she becomes pregnant. If it has been more than the recommended time interval since the last cervical cancer screen, or if there are any questions about the status of the cervix, the healthcare practitioner may suggest screening pre-conception or at the beginning of the pregnancy.

Early detection of high-risk types of HPV, abnormal cervical cells, and infections and early treatment, if necessary, offer the best chance to prevent any problems from progressing and potentially affecting the health of the baby and the success of the pregnancy.

Infection with hepatitis viruses causes inflammation of the liver. People with acute hepatitis B or hepatitis C may have symptoms such as fatigue, nausea, and jaundice. Most people will get better without any intervention, but some may develop a chronicinfection. Some of those chronically infected will have progressive liver damage that can lead to liver cancer and death.

Hepatitis B: the hepatitis B screening test is called hepatitis B surface antigen. It detects a protein produced by the virus and can detect a hepatitis B infection even before it causes symptoms. If a woman who is considering getting pregnant tests positive for hepatitis B, she should talk to her healthcare practitioner about how long she should wait to allow the infection to resolve before becoming pregnant.

It is important to detect active hepatitis B infections in pregnant women because newborns are especially vulnerable to developing chronic infection; up to 90% of those who become infected with hepatitis B in utero will become carriers. If a hepatitis infection is detected in a pregnant woman, she can be monitored and the baby can receive treatment at birth to minimize the risk of it developing hepatitis B.

A negative test for the virus means either that there is no current infection or there is not yet a sufficient amount of the antigen to be detected. If a woman participates in high-risk activities that may transmit the hepatitis B virus (such as unprotected sexual contact or intravenous drug use), retesting later in the pregnancy is generally advised.

Hepatitis C: though not common, hepatitis C can be passed from a mother to her baby. Screening of pregnant women is not routine but may be done if the mother is at risk of infection. Risk factors for hepatitis C include abusing intravenous drugs or having a sexual partner who abuses intravenous drugs, having a history of multiple sexually transmitted diseases, and being infected with hepatitis B.

Antibody tests are used to screen for the infection. Since the antibody test can remain positive in most people even if they have cleared the infection, a positive antibody test is followed by a hepatitis C RNA test, which detects genetic material of the virus. A positive result on the RNA test means the virus is present, the infection has not resolved, and the person may require treatment. The hepatitis C genotype test determines which type of virus is present to help guide treatment.