Oligohydramnios sequence

Definition

Oligohydramnios sequence occurs as a result of having very little or no fluid (called amniotic fluid) surrounding a developing fetus during a pregnancy. "Oligohydramnios" means that there is less amniotic fluid present around the fetus than normal. A "sequence" is a chain of events that occurs as a result of a single abnormality or problem. Oligohydramnios sequence is therefore used to describe the features that a fetus develops as a result of very low or absent amount of amniotic fluid. In 1946, Dr. Potter first described the physical features seen in oligohydramnios sequence. Because of his description, oligohydramnios sequence has also been known as Potter syndrome or Potter sequence.

Description

During a pregnancy, the amount of amniotic fluid typically increases through the seventh month and then slightly decreases during the eighth and ninth months. During the first 16 weeks of the pregnancy, the mother's body produces the amniotic fluid. At approximately 16 weeks, the fetal kidneys begin to function, producing the majority of the amniotic fluid from that point until the end of the pregnancy. The amount of amniotic fluid, as it increases, causes the space around the fetus (amniotic cavity) to expand, allowing enough room for the fetus to grow and develop normally.

Oligohydramnios typically is diagnosed during the second and/or third trimester of a pregnancy. When the oligohydramnios is severe enough and is present for an extended period of time, oligohydramnios sequence tends to develop. There are several problems that can cause oligohydramnios to occur. Severe oligohydramnios can develop when there are abnormalities with the fetal renal system or when there is a constant leakage of amniotic fluid. Sometimes, the cause of the severe oligohydramnios is unknown.

Approximately 50% of the time, fetal renal system abnormalities cause severe oligohydramnios, resulting in the fetus developing oligohydramnios sequence. This is because if there is a problem with the fetal renal system, there is the possibility that not enough amniotic fluid is being produced. Renal system abnormalities that have been associated with the development of oligohydramnios sequence include, the absence of both kidneys (renal agenesis ), bilateral cystic kidneys, absence of one kidney with the other kidney being cystic, and obstructions that blocks the urine from exiting the renal system. In a fetus affected with oligohydramnios sequence, sometimes the renal system abnormality is the only abnormality the fetus has. However, approximately 54% of fetuses with oligohydramnios sequence due to a renal system abnormality will have other birth defects or differences with their growth and development. Sometimes the presence of other abnormalities indicates that the fetus may be affected with a syndrome or condition in which a renal system problem can be a feature. Renal system abnormalities in a fetus can also be associated with certain maternal illnesses, such as insulin dependant diabetes mellitus, or the use of certain medications during a pregnancy.

Severe oligohydramnios can also develop even when the fetal renal system appears normal. In this situation, often the oligohydramnios occurs as the result of chronic leakage of amniotic fluid. Chronic leakage of amniotic fluid can result from an infection or prolonged premature rupture of the membranes that surround the fetus (PROM). In chronic leakage of amniotic fluid, the fetus still produces enough amniotic fluid, however, there is an opening in the membrane surrounding the fetus, causing the amniotic fluid to leak out from the amniotic cavity.

Genetic profile

The chance for oligohydramnios sequence to occur again in a future pregnancy or in a family member's pregnancy is dependant on the underlying problem or syndrome that caused the oligohydramnios sequence to develop. There have been many fetuses affected with oligohydramnios sequence where the underlying cause of the severe oligohydramnios has been a genetic abnormality. However, not all causes of severe oligohydramnios that result in the development of oligohydramnios sequence have a genetic basis. The genetic abnormalities that have caused oligohydramnios developing during a pregnancy include a single gene change, a missing gene, or a chromosome anomaly.

Although some fetuses with oligohydramnios sequence have been found to have a chromosome anomaly, the likelihood that a chromosome anomaly is the underlying cause of the renal system anomaly or other problem resulting in the severe oligohydramnios is low. A chromosome anomaly can be a difference in the total number of chromosomes a fetus has (such as having an extra or missing chromosome), a missing piece of a chromosome, an extra piece of a chromosome, or a rearrangement of the chromosomal material. Some of the chromosome anomalies can occur for the first time at the conception of the fetus (sporadic), while other chromosome anomalies can be inherited from a parent. Both sporadic and inherited chromosome anomalies have been seen in fetuses with oligohydramnios sequence. The chance for a chromosome anomaly to occur again in a family is dependent on the specific chromosome anomaly. When the chromosome anomaly is considered to be sporadic, the chance for chromosome anomaly to occur again in a pregnancy is 1% added to the mother's age-related risk to have a baby with a chromosome anomaly. If the chromosome anomaly (typically a rearrangement of chromosomal material) was inherited from a parent, the recurrence risk would be based on the specific chromosome arrangement involved. However, even if a chromosome anomaly were to recur in a future pregnancy, it does not necessarily mean that the fetus would develop oligohydramnios that could cause the development of oligohydramnios sequence.

Many of the genetic conditions that can cause oligohydramnios sequence are inherited in an autosomal recessive manner. An autosomal recessive condition is caused by a difference in a gene. Like chromosomes, the genes also come in pairs. An autosomal recessive condition occurs when both genes in a pair don't function properly. Typically, genes don't function properly because there is a change within the gene causing it not to work or because the gene is missing. An individual has an autosomal recessive condition when they inherit one non-working gene from their mother and the same non-working gene from their father. These parents are called "carriers" for that condition. Carriers of a condition typically do not exhibit any symptoms of that condition. With autosomal recessive inheritance , when two carriers for the same condition have a baby, there is a 25% chance for that baby to inherit the condition. There are several autosomal recessive conditions that can cause fetal renal abnormalities potentially resulting in the fetus to develop oligohydramnios sequence.

Oligohydramnios sequence has also been seen in some fetuses with an autosomal dominant conditions. An autosomal dominant condition occurs when only one gene in a pair does not function properly or is missing. This non-working gene can either be inherited from a parent or occur for the first time at conception. There are many autosomal dominant conditions where affected family members have different features and severity of the same condition. If a fetus is felt to have had oligohydramnios sequence that has been associated with an autosomal dominant condition, it would have to be determined if the condition was inherited from a parent or occurred for the first time. If the condition was inherited from a parent, that parent would have a 50% chance of passing the condition on with each future pregnancy.

Sometimes the fetus with oligohydramnios sequence has a condition or syndrome that is known to occur sporadically. Sporadic conditions are conditions that tend to occur once in a family and the pattern of inheritance is unknown. Since there are some families where a sporadic condition has occurred more than one time, a recurrence risk of approximately 1% or less is often given to families where only one pregnancy has been affected with a sporadic condition.

Sometimes examinations of family members of an affected pregnancy can help determine the exact diagnosis and pattern of inheritance. It is estimated that approximately 9% of first-degree relatives (parent, brother, or sister) of a fetus who developed oligohydramnios sequence as a result of a renal abnormality, will also have renal abnormalities that do not cause any problems

or symptoms. It is important to remember that if a pregnancy inherits a condition that is associated with oligohydramnios sequence, it does not necessarily mean that the pregnancy will develop oligohydramnios sequence. Therefore, for each subsequent pregnancy, the risk is related to inheriting the condition or syndrome, not necessarily to develop oligohydramnios sequence.

Demographics

There is no one group of individuals or one particular sex that have a higher risk to develop oligohydramnios sequence. Although, some of the inherited conditions that have been associated with oligohydramnios sequence may be more common in certain regions of the world or in certain ethnic groups.

Signs and symptoms

With severe oligohydramnios, because of the lack of amniotic fluid, the amniotic cavity remains small, thereby constricting the fetus. As the fetus grows, the amniotic cavity tightens around the fetus, inhibiting normal growth and development. This typically results in the formation of certain facial features, overall small size, wrinkled skin, and prevents the arms and legs from moving.

The facial features seen in oligohydramnios sequence include a flattened face, wide-set eyes, a flattened, beaked nose, ears set lower on the head than expected (low-set ears), and a small, receding chin (micrognathia).

Because the movement of the arms and legs are restricted, a variety of limb deformities can occur, including bilateral clubfoot (both feet turned to the side), dislocated hips, broad flat hands and joint contractures (inability for the joints to fully extend). Contractures tend to be seen more often in fetuses where the oligohydramnios occurred during the second trimester. Broad, flat hands tend to be seen more often in fetuses where the oligohydramnios began during the third trimester.

Fetuses with oligohydramnios sequence also tend to have pulmonary hypoplasia (underdevelopment of the lungs). The pulmonary hypoplasia is felt to occur as a result of the compression of the fetal chest (thorax), although it has been suggested that pulmonary hypoplasia may develop before 16 weeks of pregnancy in some cases. Therefore, regardless of the cause of the severe oligohydramnios, the physical features that develop and are seen in oligohydramnios sequence tend to be the same.

Diagnosis

An ultrasound examination during the second and/or third trimester of a pregnancy is a good tool to help detect the presence of oligohydramnios. Since oligohydramnios can occur later in a pregnancy, an ultrasound examination performed during the second trimester may not detect the presence of oligohydramnios. In pregnancies affected with oligohydramnios, an ultrasound examination can be difficult to perform because there is less amniotic fluid around the fetus. Therefore, an ultrasound examination may not be able to detect the underlying cause of the oligohydramnios.

In some situations, an amnioinfusion (injection of fluid into the amniotic cavity) is performed. This can sometimes help determine if the cause of the oligohydramnios was leakage of the amniotic fluid. Amnioinfusions may also be used to help visualize the fetus on ultrasound in attempts to detect any fetal abnormalities.

Additionally, maternal serum screening may detect the presence of oligohydramnios in a pregnancy. Maternal serum screening is a blood test offered to pregnant women to help determine the chance that their baby may have Down syndrome , Trisomy 18 , and spina bifida . This test is typically performed between the fifteenth and twentieth week of a pregnancy. The test works by measuring amount of certain substances in the maternal circulation.

Alpha-fetoprotein (AFP) is a protein produced mainly by the fetal liver and is one of the substances measured in the mother's blood. The level of AFP in the mother's blood has been used to help find pregnancies at higher risk to have spina bifida. An elevated AFP in the mother's blood, which is greater than 2.5 multiples of the median (MoM), has also been associated with several conditions, including the presence of oligohydramnios in a pregnancy. Since oligohydramnios is just one of several explanations for an elevated AFP level, an ultrasound examination is recommended when there is an elevated AFP level. However, not all pregnancies affected with oligohydramnios will have an elevated AFP level, some pregnancies with oligohydramnios will have the AFP level within the normal range.

Because fetuses with oligohydramnios sequence can have other anomalies, a detailed examination of the fetus should be performed. Knowing all the abnormalities a fetus has is important in making an accurate diagnosis. Knowing the cause of the oligohydramnios and if it is related to a syndrome or genetic condition is essential in predicting the chance for the condition to occur again in a future pregnancy. Sometimes the fetal abnormalities can be detected on a prenatal ultrasound examination or on an external examination of the fetus after delivery. However, several studies have shown that an external examination of the fetus can miss some fetal abnormalities and have stressed the importance of performing an autopsy to make an accurate diagnosis.

Treatment and management

There is currently no treatment or prevention for oligohydramnios sequence. Amnioinfusions, which can assist in determining the cause of the oligohydramnios in a pregnancy, is not recommended as a treatment for oligohydramnios sequence.

Prognosis

Pregnancies affected with oligohydramnios sequence can result in miscarriages, stillbirths, or death shortly after birth. This condition is almost always fatal because the lungs do not develop completely (pulmonary hypoplasia).

Resources

BOOKS

Larsen, William J. Human Embryology. Churchill Livingstone, Inc. 1993.

PERIODICALS

Christianson, C., et al. "Limb Deformations in Oligohydramnios Sequence." American Journal of Medical Genetics 86 (1999): 430-433.

Curry, C. J. R., et al. "The Potter Sequence: A Clinical Analysis of 80 Cases." American Journal of Medical Genetics 19 (1984): 679-702.

Locatelli, Anna, et al. "Role of amnioinfusion in the management of premature rupture of the membranes at less than 26 weeks' gestation." American Journal of Obstetrics and Gynecology 183, no. 4 (October 2000): 878-882.

Newbould, M. J., et al. "Oligohydramnios Sequence: The Spectrum of Renal Malformation." British Journal of Obstetrics and Gynaecology 101 (1994): 598-604.

Scott, R. J., and S. F. Goodburn. "Potter's Syndrome in the Second Trimester-Prenatal Screening and Pathological Findings in 60 cases of Oligohydramnios Sequence." Prenatal Diagnosis 15 (1995): 519-525.

Sharon A. Aufox, MS, CGC