Birth defects

• Birth defects can cause disabilities and even death.
• Alcohol and drug use while pregnant can cause birth defects.
• Ask your provider what you can do to prevent birth defects.

• Kidneys, a pair of organs that filter wastes from the blood and form urine
• Ureters, two tubes, each one leading from the kidney to the bladder
• Bladder, the sac that holds urine
• Urethra, the tube that drains urine out of the body from the bladder
• Male genitals, including the penis, prostate gland and testes
• Female genitals, including the vagina, uterus, fallopian tubes and ovaries

Abnormalities of the genitals and urinary tract are among the most common birth defects. Some of these abnormalities are minor and may cause no symptoms (example: having two ureters leading from one kidney to the bladder). Such minor defects often go undiagnosed unless the child has an X-ray, ultrasound examination or surgery for a related or unrelated problem. Other abnormalities can cause problems such as urinary tract infections, blockages, pain, and kidney damage or failure.

What is the cause of genital and urinary tract defects?
A few genital and urinary tract defects are inherited from parents who have the disorder or carry the gene for it. However, specific causes of most of these conditions are unknown. Both genetic and environmental factors may contribute to these defects. A family with an affected child should consult a genetic counselor, geneticist or a physician who is familiar with genetic disorders. These experts can discuss what is known about the cause of the specific defect and what the risks may be that the defect or disorder will occur again in subsequent offspring.

How are urinary tract defects diagnosed?
Many urinary tract defects can be diagnosed before birth with an ultrasound examination. Ultrasound uses sound waves to examine the internal organs of the fetus. After birth, ultrasound and/or a number of other tests may be recommended to provide more information on how well the kidneys and other urinary tract structures are functioning.

What are the most common urinary tract defects?
Some of the most common urinary tract defects include: renal agenesis, hydronephrosis, polycystic kidney disease, multicystic kidneys, bladder exstrophy and epispadias, hypospadias and ambiguous genitals.

What is renal agenesis?
Renal agenesis is the absence of one or both kidneys. About 1 in 6,000 babies is born with neither kidney (bilateral renal agenesis) (1). Babies with no kidneys cannot survive. More than one-third of these babies are stillborn, and the rest die in the first days of life (1).

Babies with bilateral renal agenesis often have birth defects affecting other organs, such as the heart and lungs. A fetus that has no kidneys cannot produce urine, a major part of the amniotic fluid. Because an adequate amount of amniotic fluid is crucial for normal fetal lung development, most of these babies die due to underdeveloped lungs. Lack of amniotic fluid also contributes to abnormal facial features and limb defects seen in these babies.

Between 1 in 500 and 1 in 1,000 babies are born with a single kidney (unilateral renal agenesis) (1). In most cases, children with one kidney have no symptoms and grow and develop normally. Because some children with one kidney have other urinary tract defects, tests may be recommended to see if there any other problems requiring treatment.

What is hydronephrosis?
Hydronephrosis is swelling of one or both kidneys. It occurs when a blockage somewhere in the urinary tract causes urine to back up into the kidneys. This is one of the most common fetal problems seen during a prenatal ultrasound examination, affecting about 1 in 300 pregnancies (2). Most fetal hydronephrosis resolves without lasting problems (2). However, in serious cases, the urine blockage can damage the developing kidneys or threaten the life ot the fetus.

A number of defects in the urinary tract can cause blockages and hydronephrosis. Some common ones include:

• Posterior urethral valves: An abnormal flap of tissue in the urethra prevents urine from flowing normally out of the bladder. In severe cases, the fetus's bladder becomes swollen with urine, and the urine backs up and may damage or destroy the kidneys.
• Vesicoureteral reflux: Valves located where the ureter(s) attach to the bladder fail to close properly, allowing urine to back up from the bladder into the kidneys.
• Pelvic junction obstruction: Various defects can cause a blockage where the ureter connects to the kidney.

When hydronephrosis is diagnosed before birth, the doctor will monitor the fetus with repeated ultrasound examinations to see if the condition resolves or is worsening. In most cases, no treatment is necessary until after the baby is born. After birth, many mild cases of hydronephrosis resolve themselves without treatment. If the obstruction does not resolve, surgery often is recommended in the first year or two of life to prevent further kidney damage, urinary tract infections and pain.

Occasionally, hydronephrosis can become life-threatening before birth. In such cases, a small tube called a shunt may be inserted into the fetus's bladder to drain urine into the amniotic fluid until birth, when the blockage can be repaired. Prenatal treatment of these obstructions has been the most successful form of fetal surgery to date..

What is polycystic kidney disease?
Polycystic kidney disease (PKD) is an inherited disorder that results in the growth of numerous cysts in the kidneys, reduced kidney function and, often, kidney failure. There are two main forms of the disorder: autosomal dominant and autosomal recessive PKD. Besides kidney failure, both forms can cause frequent urinary tract infections, pain, high blood pressure and other problems.

Autosomal dominant PKD is one of the most common genetic disorders, affecting between 1 in 500 and 1 in 1,000 individuals of all ages (3). It most often is inherited from a parent who has the disease, although about 10 percent of cases occur in individuals without a family history of the disease (3). Symptoms usually begin between the ages of 30 and 40, although children can sometimes be affected.

Autosomal recessive PKD is a rare form of the disease that affects children, with cysts sometimes developing before birth. About 1 in 20,000 to 1 in 40,000 babies are born with the disorder (3). Severely affected babies die in the first days of life, while others with a milder version may live into their teens or twenties (4). This form of PKD is inherited when both parents (who are unaffected) pass along the gene for the disorder to their child.

Drug treatment can control PKD-related problems such as high blood pressure and urinary tract infections. If kidney failure develops, the patient is treated regularly with dialysis and sometimes with a kidney transplant.

What is multicystic dysplastic kidney?
Kidney cysts are a feature of certain other disorders. These include multicystic dysplastic kidney, which affects about 1 in 4,000 babies (1). In this disorder, kidney tissue is replaced by cysts, resulting in a kidney that functions poorly or not at all.

Multicystic dysplastic kidney can cause death in the newborn period when both kidneys are affected. It is believed that multicystic dysplastic kidney results from an obstruction in the urinary tract during the early stages of development. Babies with only one affected kidney may have few consequences, such as urinary tract infections. While the affected kidney often does not function (and, in some cases, may need to be removed), an affected child can live a normal life with one healthy kidney.

Kidney cysts also can be a feature of a number of genetic syndromes. In many cases, such cysts cause few or no problems.

What are bladder exstrophy and epispadias?
Bladder exstrophy is a malformation of the bladder in which the bladder is turned inside out and located on the outside of the abdomen. In addition, the skin on the lower abdomen does not form properly, the pelvic bones are widely spaced, and there may be genital abnormalities. Bladder exstrophy occurs in about 1 in 30,000 births, affecting boys slightly more often than girls (5).

Epispadias is a related defect involving the urethra and genitals. It often accompanies bladder exstrophy, but it may occur by itself. In boys, the urethra often is short and split, with an opening on the upper surface of the penis. The penis itself appears short and flat. In girls, the clitoris may be split, and the urinary opening also is abnormally placed. Up to half of children with epispadias have bladder control problems.

Bladder exstrophy and epispadias can be repaired surgically. Many affected children require a number of surgeries over the first several years of life to achieve bladder control and normal-appearing genitals. In children with bladder exstrophy, the first surgery usually is performed within 48 hours of birth to close the bladder and replace it in the pelvis, close the abdominal wall and bring the pelvic bones into their correct position. Genital repair often is done around 6 to 12 months of age (5). Additional surgery to control urine leakage may be done around 4 to 5 years of age (5). Studies show that up to 90 percent of affected children can control their bladders following these surgeries (5).

What is hypospadias?
Hypospadias is a common birth defect of the penis that affects at least 1 in 300 baby boys (5). The urethra does not extend to the tip of the penis; instead, the opening of the urethra is located somewhere along the underside of the penis.

Hypospadias generally is diagnosed during the newborn examination in the hospital nursery. Affected boys should not be circumcised because the foreskin (which is removed by circumcision) may be needed to help surgically repair the defect. Surgery, which extends the urethra to the tip of the penis, usually is performed between the ages of 3 and 18 months (5). Without surgery, most affected boys would have to urinate sitting down and, as adults, would suffer pain during intercourse.

What are ambiguous genitals?
Babies who are born with ambiguous genitals have external genital organs that do not appear clearly male or female, or have features of both. For example, a girl may be born with a large clitoris that resembles a penis, or a boy may have testicles with female-like external genitals. An estimated 1 in 4.500 babies are affected. There are many causes of ambiguous genitals, including genetic disorders, hormonal disturbances, enzyme deficiencies, and gene-environment interactions.

The most common cause of ambiguous genitals is an inherited disorder called congenital adrenal hyperplasia (CAH) (5). CAH involves an enzyme deficiency that causes the adrenal glands to produce excess amounts of male hormones (androgens). The excess androgens cause the clitoris of a girl with CAH to grow too large, resembling a penis. A severe form of the disorder can affect kidney function and may cause death. Individuals with CAH require lifelong treatment with the missing hormones. Affected girls may require surgery to correct the appearance of their genitals.

(Women who have had a baby with CAH can have a prenatal test called chorionic villus sampling in subsequent pregnancies. This test can diagnose CAH early in pregnancy, allowing for prenatal drug treatment that sometimes can prevent genital defects.)

Another common cause of ambiguous genitals is androgen insensitivity syndrome. Affected babies have male chromosomes (XY) but, due to genetic defects, their cells do not respond or respond incompletely to androgens (male hormones). Babies with complete androgen insensitivity have testes (which usually remain inside the abdomen) and female external genitals, although they do not have a uterus or ovaries. These children are generally raised as girls and have a completely normal female appearance. Babies with partial androgen sensitivity have cells that partially respond to androgens, and often have ambiguous external genitals. Some of these children may be raised as males, and others as females, depending on their individual situation. These children generally need hormone treatment to undergo pubertal changes.

A number of chromosomal abnormalities can cause ambiguous genitals. These include gonadal dysgenesis, in which the baby has normal male chromosomes (XY), but does not develop normal testes. Children with complete gonadal dysgenesis have female external genital organs and underdeveloped female internal organs. with either female internal and external genital organs, or ambiguous external genitals and some combination of male and female internal organs. They are generally raised as girls and are treated with female hormones at puberty. Children with partial gonadal dysgenesis have some testicular tissue, some female internal sex organs and ambiguous external genitals. Depending on their individual situation, some of these children are raised as females and others as males. They should receive treatment with the appropriate hormones at puberty.

When a child is born with ambiguous genitals, health care providers do a number of diagnostic tests to help determine the baby's gender. These include physical examination, blood tests (including chromosomal analysis and measurement of the levels of various hormones), a pelvic ultrasound examination and, sometimes, surgery to look at the internal organs. A team of medical specialists use these tests to help determine whether the baby is developing more like a male or female, and they may recommend assigning a gender for the baby.

At some point, reconstructive surgery may be performed to give the genitals a more normal appearance. However, each patient is different, and the timing of surgery must be individualized. Decisions about surgery should be collaborative, involving physicians, the family and the child (when developmentally appropriate). (Surgery for health reasons should not be postponed. For example, certain internal organs not appropriate for the child’s gender may be more likely to develop cancer, so they are often removed.) Having ambiguous genitals can be extremely difficult for the child and family, so ongoing psychological counseling is strongly recommended.

For more information

• National Kidney and Urologic Diseases Information Clearinghouse 
• American Urological Association

References

1. Norwood, V.F. and Chevalier, R.L. Renal Developmental Disorders of the Fetus and Newborn, in: Rudolph C.D., and Rudolph, A.M.(eds.), Rudolph’s Pediatrics, 21st edition. New York, NY, McGraw-Hill, 2003, pages 1638-1642.
2. Small, M.J., and Copel, J.A. Practical Guidelines for Diagnosing and Treating Fetal Hydronephrosis. Contemporary Ob/Gyn, February 2004, pages 59-77.
3. National Institutes of Health. Genetics Home Reference: Polycystic Kidney Disease. June 2006.
4. National Institutes of Health. Polycystic Kidney Disease. National Kidney and Urologic Diseases Clearinghouse, June 2007.
5. American Urological Association. Accessed 9/10/07.
6. Hughes, I.A., et al. Consensus Statement on Management of Intersex Disorders. Archives of Disease in Childhood, volume 91, 2006, pages 554-563.

November 2007