Birth Defects and Congenital Anomalies

Most birth defects are caused by genetic or environmental factors or a combination of the two (multifactorial birth defects). In most cases, however, the cause is unknown.

Genetic or inherited causes include:

• Chromosomal defects: caused by too few or too many chromosomes, or problems in the structure of the chromosomes, such as Down syndrome and extra copy of chromosome 21 and sex chromosome abnormalities
• Single gene defects: a mutation in one gene causes the defect
• Dominant inheritance: when one parent (who may or may not have the disease) passes along a single faulty gene, such as achondroplasia and Marfan syndrome
• Recessive inheritance: when both parents, who do not have the disease, pass along the gene for the disease to the child, such as cystic fibrosis and GM2 gangliosidosis (Tay-Sachs disease)

An environmental cause can include drugs, alcohol, or a disease the mother has that can increase the chance for the baby to be born with a birth defect. An agent that can cause a birth defect is known as a teratogen.

Multifactorial birth defects are caused by a combination of genes and environmental exposures. In other words, a person can inherit a gene that increases sensitivity to an environmental trigger. Examples include cleft lip or palate, certain heart defects, and neural tube defects.

There are many steps a woman can take to lower her chances of having a child with a birth defect, including staying healthy before deciding to become pregnant. That's because a woman often does not know she is pregnant in the first few weeks, which can be crucial for the health and development of the baby.

Other steps you can take throughout your pregnancy include:

• Stop smoking: Babies born to mothers who smoke tend to be lower birthweight; in addition exposure to secondhand smoke can harm the fetus.
• Eat a healthy diet: Eating a balanced diet before and during pregnancy is not only good for the mother's overall health, but essential for providing the developing fetus with essential nutrients for proper growth and development.
• Maintain a healthy weight: Women who are overweight may experience medical problems such as high blood pressure and diabetes, and women who are underweight may have babies with low birthweight.
• Medical management of preexisting conditions: Take control of any current or preexisting medical problems, such as diabetes or high blood pressure.
• Folic acid: Taking 400 micrograms of folic acid each day can help lower the risk of neural tube defects, or birth defects of the brain and spinal cord. The vitamin is also found in some green leafy vegetables, nuts, beans, citrus fruits, and fortified breakfast cereals.
• Avoid exposure to alcohol and drugs during pregnancy: Be sure to inform your physician of any medications and herbal supplements you are taking, since they can all have adverse effects on the developing fetus.
• Avoid exposure to harmful substances: These include lead, pesticides, and radiation (i.e., x-rays), which may harm the developing fetus.
• Lower your risk for infection. Pregnant women should avoid eating undercooked meat and raw eggs and avoid all contact and exposure to cat feces and cat litter, which may contain a parasite, toxoplasma gondii, that causes toxoplasmosis. Other sources of infection include insects that have been in contact with cat feces.
• Take a daily vitamin: Begin taking a prenatal vitamin daily, prescribed by your doctor, to make sure your body gets all the necessary nutrients and vitamins needed to nourish a healthy baby.
• Dealing with domestic violence: Women who are abused before pregnancy may be at risk for increased abuse during pregnancy. Your doctor can help you find community, social, and legal resources to help you deal with domestic violence.

Some birth defects can be diagnosed before birth through ultrasound, amniocentesis, or chronic villus sampling (CVS). Most women have blood tests to screen for their risk of having a baby with a specific birth defect, such as Down syndrome and spina bifida. While it does not usually lead to a cure for the baby's birth defect, prenatal diagnosis can prepare the parents emotionally and help them prepare for a child with a birth defect.

In other cases a birth defect is diagnosed after birth through physical examination or a blood test that screens for several disorders in newborns.

A preconception examination, also known as a preconception visit, is one of the best ways to ensure a healthy pregnancy. The goals are to assess your overall health and identify any risk factors that can complicate a pregnancy. A preconception examination can include any of the following:

Family medical history

A doctor will assess the medical history of both of your biological parents to see if any family member has had medical problems such as high blood pressure, diabetes, or mental retardation.

Genetic testing

A doctor will assess any possible genetic disorders that can be passed down to your child; some genetic disorders can be detected by blood tests before pregnancy.

Personal Medical History: to determine if you have any medical conditions that may require special care during pregnancy (anemia, epilepsy, diabetes, high blood pressure); to gather information about previous surgeries; and to obtain information about past pregnancies such as complications, losses, and length of gestation.

Vaccination status

To assess immunity to diseases such as rubella (German measles) that can cause miscarriage or birth defects, a vaccine can be given at least three months prior to conception to provide immunity.

Infection screening

Infection screening determines if a woman has a sexually transmitted infection, a urinary tract infection, or another type of infection that can be harmful to her or to the fetus.

Most birth defects cannot be cured. Treatment focuses on managing the symptoms. In some cases, however, there are ways to treat specific birth defects.

Gene therapy

Gene therapy replaces a gene that is either missing or defective. Severe combined immunodeficiency diseases (SCID) are a group of very rare diseases for which gene therapy has been used.

Enzyme replacement therapy

Enzymes are proteins for which genes code. So when a gene is mutated and does not produce the gene product, an enzyme is missing or defective. One way to treat this type of genetic defect is to replace the enzyme that the gene is not producing. An example of a condition for which enzyme replacement therapy has been developed is Gaucher disease.

Prenatal treatment

Some birth defects can be diagnosed and treated before birth. Prenatal surgery, for instance, can treat babies with urinary tract blockages and rare lung tumors.

The Fetal Care and Surgery Center is one of a handful of comprehensive fetal care centers in the United States, and the only one in New England. The FCSC treats, supports, and manages complicated fetal anomalies. Its doctors were the world's first to perform life-saving cardiac interventions, such as treating heart problems in utero. The center is also advancing treatments for congenital diaphragmatic hernia, a condition in which a baby is born with a hole in the diaphragm or no diaphragm at all.

When pregnant women need medications, there’s often concern about possible effects on the fetus. Although some drugs are clearly recognized to cause birth defects (thalidomide being a notorious example), and others are generally recognized as safe, surprisingly little is known about most drugs' level of risk. Researchers in the Boston Children's Hospital Informatics Program (CHIP) have created a preclinical model for predicting a drug's teratogenicity (tendency to cause fetal malformations) based on characterizing the genes that it targets.

The model used bioinformatics and public databases to profile 619 drugs already assigned to a pregnancy risk class, and whose target genes or proteins — over 7,000 in all — are known. For each drug, CHIP investigators Asher Schachter, MD, MMSc, MS, and Isaac Kohane, MD, PhD, identified the number of targeted genes likely to be involved in fetal development, using telltale search terms like "genesis," "develop," "differentiate," or "growth." The drugs targeting a large proportion of genes associated with fetal development tended to be in the higher risk classes.

Based on the developmental gene profile, the researchers created a model that showed 79 percent accuracy in predicting whether a drug would be in Class A (safest) or Class X (known teratogen). "We can't provide a yes/no answer,” says Schachter, “but we found a pattern that can predict which are riskier."

Schachter and Kohane believe their model may be of interest to drug developers and prescribing physicians, and might provide useful information to incorporate in drug labeling. (Reproductive Toxicology, March 2011)