Polyhydramnios - Polyhydramnios

Polyhydramnios is a condition in which the pregnant uterus contains too much amniotic fluid [A pathologic accumulation of amniotic fluid volumes greater than 2,000 mL] .

The definition of "too much" is generally considered to be more than 2 liters; the average amount is about 1 liter.

Most cases of polyhydramnios are mild and involve less than 3 liters of amniotic fluid.

So, in many cases, a diagnosis of polyhydramnios means that you're on the high side of normal for amount of amniotic fluid and presents only minor secondary concerns.

In general, the causes of polyhydramnios are due to either excessive production of fluid or inadequate utilization or removal of fluid. Interestingly, greater than 65 percent of cases of polyhydramnios are due to unknown causes. However, it is important to look for causes via ultrasound.

 

 

high risk for preterm labor, preterm premature rupture of the membranes (PPROM), and increased perinatal morbidity.

Polyhydramnios occurs in about 1 pregnancy out of 100; 95% of those are considered mild to moderate.

There are essentially two major causes of polyhydramnios; reduced fetal swallowing or absorption of amniotic fluid and increased fetal urination.

 Reduced fetal swallowing may be due to

·        craniospinal defects (such as anencephaly),

·         facial tumours,

·        gastrointestinal obstruction (such as esophageal atresia,

·         duodenal atresia and small bowel obstruction),

·        compressive pulmonary disorders (such as pleural effusions, diaphragmatic hernia or cystic adenomatoid malformation of the lungs),

·        narrow thoracic cage (due to skeletal dysplasias),

·        and fetal akinesia deformation sequence (due neuromascular impairement of fetal swallowing).

·         Increased fetal urination is observed in maternal diabetes mellitus and maternal uremia (increased glucose and urea cause osmotic diuresis),

·        hyperdynamic fetal circulation due to fetal anemia (due to red cell isoimmunization or congenital infection)

·        or fetal and placental tumours or cutaneous arteriovenous malformations (such as sacrococcygeal teratoma, placental chorioangioma),

·         twin-to twin transfusion syndrome.

 Diagnosis:

The diagnosis of polyhydramnios is usually made subjectively.

Quantitatively, polyhydramnios is defined an amniotic fluid index (the sum of the vertical measurements of the largest pockets of amniotic fluid in the four quadrants of the uterus) of 20 cm or more. Alternatively, the vertical measurement of the largest single pocket of amniotic fluid free of fetal parts is used to classify polyhydramnios into mild (8-11 cm), moderate (12-15 cm) and severe (16 cm or more).

 Although 80% of cases with mild polyhydramnios are considered to be idiopathic, in the majority of cases with moderate or severe polyhydramnios there are maternal or fetal disorders.

In most cases polyhydramnios develops late in the second or in the third trimester of pregnancy.

Acute polyhydramnios at 18-24 weeks is mainly seen in association with twin-twin transfusion syndrome.

Testing for maternal diabetes, detailed sonographic examination for anomalies, and fetal karyotyping should constitute the cornerstones of the diagnostic protocol in the investigation of these cases.

 

Moderate polyhydramnios

Polyhydramnios - Diaphragmatic Hernia

Some background on amniotic fluid: As with many issues in human biology, mechanisms of regulating the amount of amniotic fluid are not well understood. It is believed that amniotic fluid is manufactured by the amnion, which "weeps" to add fluid. In addition, babies urinate and sweat, also adding to the fluid. Fluid is removed from the amniotic sac when the baby swallows and the fluid is taken into the bloodstream and transferred to the mother's bloodstream via the placenta.

Maternal diabetes, which is associated with a macrosomic (enlarged) fetus, is a common cause.

The medication lithium, used to treat depression, can also increase amniotic fluid levels.

Twin gestations are prone to polyhydramnios. Infections passed from mother to fetus such as rubella, cytomegalovirus, and toxoplasmosis, can also result in damage to the fetus and elevated amniotic fluid levels.

Fetal abnormalities, including many that are life-threatening or lead to a significant impairment in the quality of life, are found in up to a quarter of all patients.

For this reason, the initial finding of excess amniotic fluid should be followed by thorough diagnostic studies to determine the cause and the prognosis.

Because fetal swallowing is a major factor in amniotic fluid removal, fetal abnormalities that prevent fluid uptake should be investigated.

These include gastrointestinal obstructions such as

 esophageal atresia and

 duodenal atresia,

 as well as neurological conditions that affect swallowing including anencephaly.

Certain cardiac abnormalities,

kidney disorders,

 and genetic conditions such as myotonic dystrophy and alpha-thalassemia can also cause polyhydramnios.

Fetal chromosome abnormalities are frequently associated with elevated amniotic fluid levels.

 The more severe the polyhydramnios the more likely it is that fetal abnormalities will be present.

 In addition, there are other, infrequent causes, and in a number of cases, no cause can be found. Polyhydramnios can lead to maternal abdominal discomfort and respiratory difficulties as well as preterm labor. When polyhydramnios is associated with fetal abnormalities, perinatal mortality is significantly increased.

 

The cause is rarely known for certain, but a diagnosis of polyhydramnios will usually result in a search to find the cause, typically through ultrasound. The ultrasound may or may not reveal the likely cause in the form of a fetal abnormality.

 

Common Causes:
  • esophageal atresia
  • duodenal atresia
  • anencephaly
  • hydrops fetalis
  • achondroplasia
  • Beckwith-Wiedemann syndrome
  • diaphragmatic hernia
  • hydrops fetalis
  • gastroschisis
  • multifetal gestations

 

Three potential mechanisms are thought to cause excess amniotic fluid in cases where fetal anomalies are associated with polyhydramnios.

Impaired fetal swallowing. Upper GI tract obstruction, neck masses (goiter or teratoma, for example), skeletal system anomalies that are associated with a narrow thorax, CNS anomalies, space-occupying lesions of the thorax (diaphragmatic hernia, pleural effusions, or congenital cystic adenomatoid malformation), and neurological deficits (for example, myotonic dystrophia) can cause impaired fetal swallowing.

Transudation of fluid across membranous lesion. Although almost all anencephalic fetuses do not swallow, only 67% develop polyhydramnios.12 This suggests that other factors, such as meningeal transudation or vasopressin (ADH) deficiency, can contribute to increased fluid in some of these cases.

Congestive heart failure caused by congenital heart disease, severe anemia, or mass lesions. The latter can either cause venous obstruction, such as congenital cystic adenomatoid malformation
of the lung, or lead to high-output failure, such as sacrococcygeal teratoma.

Acute polyhydramnios--as opposed to its chronic form--is a severe condition in which amniotic fluid rapidly increases in volume over a short period of time. Most cases occur before 24 weeks. Acute polyhydramnios is most commonly seen in twin-to-twin transfusion syndrome (TTTS), or is associated with fetal anomalies. However, cases of idiopathic acute polyhydramnios have been reported in singleton pregnancies with anatomically normal fetuses.13

Advances in maternal-fetal medicine have reduced the prevalence of polyhydramnios. The universal use of Rh immunoglobulin has significantly lowered the incidence of Rh sensitization. Widely offered diabetes screening and tight control of maternal blood sugars have led to the successful control, in many cases, of hyperglycemia. This, in turn, may have led to a decline of polyhydramnios related to that disorder

 

Oligohydramnios is most commonly associated with abnormalities of the fetal kidneys.

Since fetal urine is the main source of amniotic fluid in the latter two-thirds of pregnancy, any condition that interferes with fetal urine production can lead to oligohydramnios.

Renal agenesis, cystic kidneys, and bladder outlet obstructions are common.

Meckel-Gruber syndrome, a lethal autosomal recessive genetic disorder featuring brain and kidney abnormalities and extra digits is one specific cause.

Placental insufficiency and fetal growh retardation can also result in oligohydramnios.

 Premature rupture of membranes, especially between 16 and 24 weeks is another cause and, because amniotic fluid is important in lung growth, it can lead to underdevelopment of the lungs (pulmonary hypoplasia).

In general, regardless of the cause, oligohydramnios that arises early in a pregnancy, can cause hypoplastic lungs.

It can also result in space limitations within the amniotic sac that cause fetal compression and orthopedic abnormalities such as clubbed feet in the newborn.

 In general, oligohydramnios that begins near the time of delivery is associated with a better outcome than cases than have an onset earlier in pregnancy.

Oligohydramnios means reduced amniotic fluid and anhydramnios means absence of amniotic fluid.

Prevalence:

Oligohydramnios in the second trimester is found in about 1 per 500 pregnancies.

Etiology:

Oligohydramnios in the second trimester is usually the result of

·         preterm premature rupture of the membranes,

·         uteroplacental insufficiency

·          and urinary tract malformations (bilateral renal agenesis, multicystic or polycystic kidneys, or urethral obstruction).

Diagnosis:

The diagnosis of oligohydramnios is usually made subjectively.
Quantitative criteria include:
(a) the largest single pocket of amniotic fluid being 1 cm or less, or
(b) amniotic fluid index (the sum of the vertical measurements of the largest pockets of amniotic fluid in the four quadrants of the uterus) of 5 cm.

Anecoic areas simulating pockets of amniotic fluid

Color Doppler energy at the umbilical cord

 

 

In about 60% of cases of polyhydramnios, there is a mild to moderate amount of excess fluid caused by more-than-adequate generation of fluid by the amniotic sac.

 The mother and baby are completely normal, and the only concerns are the mechanical issues relating to the large amount of fluid at labor and delivery.

This type of polyhydramnios tends to appear after about the 30th week, when there is a gradual increase in the amount of fluid.

 It is detected by higher-than-average growth of the uterus, difficulty in feeling the outline of the baby because of the generous amount of fluid, difficulty in hearing the baby's heart because of the amount of fluid, and the ability to create waves in the fluid.

 It tends to stabilize in volume or increase very gradually and is simply a variation on normal.

This is generally an indication that there are no serious congenital problems, and the only remaining concerns are the mechanical issues around labor and birth related to a large amount of amniotic fluid. (This is called "chronic hydramnios.")

Prenatal therapy of polyhydramnios:

The aim is to reduce the risk of very premature delivery and the maternal discomfort that often accompanies severe polyhydramnios. Treatment will obviously depend on the diagnosis, and will include better glycemic control of maternal diabetes mellitus, antiarrhythmic medication for fetal hydrops due to dysrrhythmias, thoraco-amniotic shunting for fetal pulmonary cysts or pleural effusions. For the other cases, polyhydramnios may be treated by repeated amniocenteses every few days and drainage of large volumes of amniotic fluid. However, the procedure itself may precipitate premature labour. An alternative and effective method of treatment is maternal administration of indomethacin; however, this drug may cause fetal ductul constriction and close monitoring by serial fetal echocardiographic studies is necessary. In twin-twin transfusion syndrome, presenting with acute polyhydramnios at 18-22 weeks of gestation endocopic laser occlusion of placental anastomoses or serial amniodrainage may be carried out.

Prostaglandin (PG) synthetase inhibitors may be effective in treating those women with polyhydramniosis in whom etiology is related to increased fetal urine output. For patients whose polyhydramniosis is related to poor fetal swallowing, however, no benefit can be expected. Base your therapeutic approach to women with polyhydramnios on an understanding of the pathophysiology of the underlying cause. PG synthetase inhibitors can be very effective in therapy for women with polyhydramnios and diabetes mellitus, and in some idiopathic cases, but avoid giving them to patients with TTTS, as they may further diminish the blood flow to an already hypoperfused donor fetus.

How critical is the time frame for a response to treatment?

Often this factor heavily influences selection of a particular treatment option. On one hand, an amnioreduction performed on a symptomatic patient with severe polyhydramnios may relieve the problem immediately. PG synthetase inhibitors, on the other hand, will take at least 24 hours to manifest their desired effect. In persistent or recurrent cases, adding PG synthetase inhibitors after amnioreduction can stabilize the AFV and avoid the necessity for serial taps. Patients with moderate polyhydramnios might be better served by being treated primarily with PG synthetase inhibitors, rather than undergoing amnioreduction. In any case, PG synthetase inhibitors should always be used cautiously and restricted to the conditions

 

 

Prognosis:

This depends on the cause of polyhydramnios

In another 20% of cases, there is a problem on the maternal side, either diabetes or a blood incompatibility with the fetus.

 These cases require close monitoring by a specialist because the cause of the polyhydramnios could represent a serious problem for the baby.

 

In another 20% of cases, there is a problem with the baby - either the baby is adding unusual amounts of fluid or is swallowing less than usual.

 A blockage of the esophagus that prevents swallowing is usually easily remedied by postpartum surgery.

 Excess amounts of fluid are thought to be caused by increased fluid coming from the exposed spinal cord or by excess urination caused by overstimulation of the exposed spinal cord, as in anencephaly or spina bifida.

It is generally accepted that polyhydramnios is associated with an increased frequency of maternal and fetal complications. Maternal problems associated with severe polyhydramnios include abdominal discomfort, respiratory embarrassment, renal failure, and uterine irritability.15-17

Uterine overdistension associated with increased intrauterine pressure may lead to PPROM and preterm labor.

The preterm delivery rate for patients with polyhydramnios and an anomalous fetus can be as high as 39%.

 Although no significant relationship has been found between the severity of polyhydramnios and preterm delivery, this may be due to the small number of patients with severe polyhydramniosis in the study groups, and to the way the authors define polyhydramnios.

 On the other hand, investigators have found that the underlying cause of polyhydramnios is related to the incidence of preterm delivery. In one study, preterm deliveries occurred in 28% of patients with polyhydramnios and insulin-dependent diabetes mellitus and in 14% of those with idiopathic polyhydramnios.

 The preterm delivery rate for patients with idiopathic polyhydramnios and gestational diabetes was not significantly higher than normal.19

Apart from preterm delivery and problems related to congenital abnormalities, other factors contributing to an adverse perinatal outcome in patients with polyhydramnios include placental abruption, cord prolapse, and uteroplacental insufficiency.

 The most important parameters that influence fetal survival are gestational age at delivery, associated congenital abnormalities, and the severity of the polyhydramnios.

 Perinatal mortality rates rise significantly when congenital abnormalities and TTTS are present.

 The above findings, however, cannot explain every case of perinatal mortality.

 Uteroplacental compromise directly caused by polyhydramnios has been reported, and the increased intra-amniotic hydrostatic pressure related to severe polyhydramnios can adversely affect umbilical cord pH and Po2.

 

Again, none of these mechanisms is understood thoroughly; there is simply evidence correlating some of these conditions. Severe cases of polyhydramnios tend to be associated more with fetal abnormalities and tend to have a worse outcome. In most mild to moderate cases, a cause is never identified and the outcomes are completely normal.

 

Severe polyhydramnios tends to appear at about the 20th week of pregnancy and tends to have a sudden onset, i.e. the uterus will have grown 8 cm in 4 weeks rather than the expected 4.

 This type of polyhydramnios is more likely a symptom of a serious congenital problem. In addition, the amount of amniotic fluid tends to increase, often to the point that the amniotic sac ruptures or premature labor begins. In many of these cases, premature delivery of an immature infant results in the death of the fetus.

 

Polyhydramnios as it Relates to Labor and Birth

 

Having a large amount of amniotic fluid can cause mechanical problems having to do with the baby's presentation, and the possibility of cord prolapse, placental abruption and postpartum hemorrhage. Let's look at each of these in turn, and consider why there's a risk and what can be done to minimize the risk.

 

THE BABY'S PRESENTATION: A baby normally settles into a nice, head down position as the growing body crowds the uterus and finds that it is best accommodated with the bulkier bottom in the roomier top of the uterus. With a lot of amniotic fluid, this will happen later in the pregnancy than usual. Occasionally, even a fullterm baby may have room to turn freely. Thus, the presentation (i.e. head down, breech or an unfavorable transverse lie) continues to change until the amount of fluid is reduced, typically when the membranes rupture. Because this can be a sudden event, the baby may be caught in an awkward transverse lie, which is impossible to birth vaginally. In addition, many practitioners are not trained in safe, vaginal delivery of breeches and consider a breech presentation an indication for a cesarean section.

 

Thus, the baby's presentation at the time the amniotic sac ruptures is a major factor in the subsequent course of the delivery. So, it is essential that some intelligence be brought to the situation. Ideally, the baby is encouraged to assume an ideal, head down position, and the membranes are ruptured very slowly, i.e. with a small pinprick to allow the waters to begin to leak out. Then the baby may be held in position until enough fluid has leaked out that the baby can no longer turn.

 

Because of the possibility of cord prolapse, this should be done by a caregiver trained in this technique. Also because of the possibility of placental abruption, it is essential that there be ready access to an emergency cesarean.

 

CORD PROLAPSE: Cord prolapse is a situation in which the umbilical cord comes before or alongside the presenting part. This is a problem because the cord may become compressed in the pelvis and blood may not be able to flow freely through it to the baby.

 

Polyhydramnios increases the risk of cord prolapse for several reasons. First, because the baby's presentation is unpredictable, the baby may be in an unfavorable position when the membranes rupture, and the presenting part may not fit into the pelvis well enough to keep the cord from falling out below. Second, because there is so much fluid, there is more pressure on the movable umbilical cord to move it out past the presenting part.

 

This risk can be minimized by managing the rupture of membranes, paying close attention to the baby's presentation. If the membranes are ruptured with a pinprick while the baby's head is held low in the pelvis, the risk of cord prolapse can be minimized.

 

PLACENTAL ABRUPTION: A placental abruption is a premature separation of the placenta from the uterine wall. This is a problem because it interferes with the free flow of blood between the maternal blood supply and the fetal circulatory system. A partial abruption may not be a serious problem, but if a significant portion of the placenta separates, the baby's oxygen supply is compromised so that the baby may begin to suffer severely from oxygen deprivation and may die. A significant placental abruption is a situation that warrants an immediate cesarean section to save the baby.

 

Polyhydramnios increases the risk of placental abruption because of the mechanical forces at work in separating the placenta from the uterus. If you can imagine a filet of tofu (this is a vegetarian explanation) glued to the top of an inflated balloon, this is sort of what a placenta looks like inside the uterus. When the balloon starts to deflate, the amount of inside surface to which the tofu is attached starts to decrease. The tofu will start to buckle and separate in places and then may shear off partially or completely. This is less likely to happen if there is a small amount of deflation, and more likely to happen if there is more deflation. (By the way, this is also the way the placenta normally separates after birth, after the baby has been born. It is only a problem if it happens before the baby's birth.)

 

When there is an unusually generous amount of amniotic fluid, the difference before and after rupture of membranes may be significant, especially if the presenting part does not fit well into the pelvis and seal the remaining fluid in the uterus. This sudden change in uterine size may cause a placental abruption. If there is only a mild to moderate amount of extra amniotic fluid, this may not be a problem. In any case, it is important that the presenting part be fit as snugly into the pelvis as possible so that the continuing production of amniotic fluid may fill the upper part of the uterus and guard against a placental abruption. (And, in a situation of polyhydramnios, this should happen even more readily than otherwise.)

 

However, given the dire consequences of a placental abruption, it is essential that there be ready access to a cesarean section until membranes have ruptured and the amount of amniotic fluid has stabilized.

 

POSTPARTUM HEMORRHAGE: Polyhydramnios increases the risk of postpartum hemorrhage simply because the uterus has been distended more than is usual for a singleton pregnancy. Thus, it can be more difficult for the uterus to contract completely, and it is essential that a diligent watch be kept to ensure that clots do not accumulate, thus making it even harder for the uterus to contract, thus causing more bleeding, more clots, etc. Diligent attention to uterine size and hardness should provide ample warning of impending postpartum hemorrhage. Massaging the uterus or nursing the baby (or otherwise stimulating the nipples) will help to keep the uterus contracted. It may be necessary to augment this with pitocin.

 

Herbals for postpartum hemorrhage: Red raspberry leaf tea can be used during pregnancy to tone the uterus, so that it contracts more effectively to prevent postpartum hemorrhage. Motherwort herb can be used after the delivery of the placenta to prevent postpartum hemorrhage, and shepherd's purse can be used to stop a postpartum hemorrhage.

 

OVERALL APPROACHES TO DELIVERY:

 

 

_Williams Obstetrics_ recommends amniocentesis to relieve maternal distress and hints that it will also lessen risks of cord prolapse and placental abruption. However, there are no other guidelines for standard obstetric management of the delivery. There is a specific guideline *not* to rupture membranes artificially because of the risks involved, but there is no discussion of how to manage the inevitable rupture of membranes intelligently.

 

Since I am a homebirth midwife, I am required to transfer or co-manage care of polyhydramnios. So I don't have a protocol for management of delivery in the presence of polyhydramnios. However, as someone who lives in Earthquake Country, I like to learn as much as possible, just in case. If, in an emergency, I were attending a homebirth delivery of a woman with polyhydramnios, I would probably do the following: Assuming the membranes were not yet ruptured, my first thoughts would be to encourage the baby to get in a head down position through slantboard exercises, homeopathics, visualization, headstands in pool if possible. If a complete version is not possible, I would help the baby at least to get into a longitudinal lie, rather than transverse. (So either head down or breech would be OK.) Once labor is well established and the presenting part engaged, I would have the woman get in a knees-chest position, have an assistant hold the presenting part low in the pelvis and put a pinprick hole in the bag of waters. Then, very slowly, while listening to the baby's heart rate, I would help the woman to assume an upright position as the waters slowly leaked out. Assuming all is well and the presenting part well engaged in the pelvis, we are then past the problems of presentation, cord prolapse and greatest danger of placental abruption. All that remains is to keep a watchful eye on things and be prepared to prevent and/or treat a postpartum hemorrhage.

 

 

BRIEF DISCUSSION OF POLYHYDRAMNIOS

 

Polyhydramnios simply means that there is more amniotic fluid than is usual. In most cases, it is just a variation on normal, appearing gradually late in the pregnancy and posing some minor additional challenges for the labor and delivery. In about 5% of cases, the condition is severe and usually correlated with a severe fetal abnormality; these cases tend to develop suddenly at about 4 or 5 months. In severe cases, a continuing increase in the amount of amniotic fluid threatens the pregnancy, which may end in premature delivery.

 

In most cases, no cause is identified; the only reason it is of any significance is that the increased amount of fluid must be dealt with intelligently in order to avoid problems in labor and delivery. Particular attention must be paid to assisting the baby in getting into a favorable position for the birth. The amniotic sac must not be allowed to rupture so that there is a sudden loss of amniotic fluid; this could cause a cold prolapse or a placental abruption. The birth attendants must be alert to prevent and treat possible postpartum hemorrhage.

 

 

Dr. Lembet is a Fellow, Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Mount Sinai Medical Center, New York, N.Y.; Dr. Berkowitz is Director, Division of Maternal-Fetal Medicine, and Chairman, Department of Ob/Gyn, Mount Sinai Medical Center, New York, N.Y.

Series Editors are Dr. Berkowitz and Mary E. D'Alton, MD, Professor of Ob/Gyn and Director of Obstetrics and Maternal-Fetal Medicine, Columbia University College of Physicians and Surgeons, New York, N.Y.

REFERENCES

1. Brace RA, Wolf EJ. Normal amniotic fluid volume changes throughout the pregnancy. Am J Obstet Gynecol. 1989;161:382-388.

2. Manning FA, Platt LD. Qualitative assessment of amniotic fluid volume. A rapid screen for detecting the small-for-gestational-age fetus. Presented at the 26th Annual Meeting of the Society for Gynecologic Investigation. San Diego, Calif. March 1,1979.

3. Chamberlain MB, Manning FA, Morrison I, et al. Ultrasound evaluation of amniotic fluid. II. The relationship of increased amniotic fluid volume to perinatal outcome. Am J Obstet Gynecol. 1984;150:250-225.

4. Phelan JP, Ahn MO, Smith CV, et al. Amniotic fluid index measurements during pregnancy. J Reprod Med. 1987;32:601-604.

5. Moore TR, Cayle JE. The amniotic fluid index in normal human pregnancy. Am J Obstet Gynecol. 1990;162:1168-1173.

6. Moore TR. Superiority of the four quadrant sum over the single deepest pocket technique in ultrasonographic identification of abnormal amniotic fluid volumes. Am J Obstet Gynecol. 1990;163:762-767.

7. Chamberlain PF, Manning FA, Morrison I, et al. Ultrasound evaluation of amniotic fluid volume. I. The relationship of marginal decreased amniotic fluid volume to perinatal outcome. Am J Obstet Gynecol. 1984;150:245-249.

8. Magann EF, Nolan TE, Hess LW, et al. Measurement of amniotic fluid volume: accuracy of ultrasonography techniques. Am J Obstet Gynecol. 1992;167:1533-1537.

9. Chauhan SP, Magann EF, Morrison JC, et al. Ultrasonographic assessment of amniotic fluid does not reflect actual amniotic fluid volume. Am J Obstet Gynecol. 1997;177:291-297.

10. Hill LM, Breckle R, Thomas ML, et al. Polyhydramnios ultrasonically detected prevalence and neonatal outcome. Obstet Gynecol. 1987;69:21-25.

11. Ben-Cherit A, Hochner-Celnikier D, Ron M, et al. Hydramnios in the third trimester of pregnancy: a change in the accompanying fetal anomalies as a result of early ultrasonographic diagnosis. Am J Obstet Gynecol. 1990;162:1344-1345.

12. Nichols J, Schrepfer R. Polyhydramnios in anencephaly. JAMA. 1966:197:549-551.

13. Queenan JT, Gadow EC. Polyhdramnios: chronic versus acute. Am J Obstet Gynecol. 1970:108:349-355.

14. Davies A, Nicholls JC. Reversal of diabetic related accelerated fetal growth by maternal glycemic control. Eur J Obstet Gynecol Reprod Biol. 1993;50:251-254.

15. Vintzileos AM, Turner GW, Campbell WA, et al. Polyhydramnios and obstructive renal failure. Am J Obstet Gynecol. 1985;152:883-885.

16. Cardwell MS. Polyhydramnios: a review. Obstet Gynecol Surv. 1987:42:612-617.

17. Kyle PM, Fisk NM. Oligohydramnios and polyhydramnios. In: Fisk NM, Moise KJ, eds. Fetal Therapy. UK: Cambridge University; 1997:203-226.

18. Many A, Hill LM, Lazebnik N, et al. The association between polyhydramnios and preterm delivery. Obstet Gynecol. 1995;86:389-391.

19. Many A, Lazebnik N, Hill LM. The underlying cause of polyhydramnios determines prematurity. Prenat Diagn. 1996;16:55-57.

20. Fisk NM, Vaughan J, Talbert D. Impaired fetal blood gas status in polyhydramnios and its relation to raised amniotic pressure. Fetal Diagn Ther. 1994; 9:7-13.

21. Milunsky JM, Skare JC, Milunsky A. Presymptomatic and prenatal diagnosis of myotonic muscular dystrophy with linked DNA probes. Am J Med Sci. 1991;301:231-237.

22. Brady K, Polzin WJ, Kopelman JN, et al. Risk of chromosomal abnormalities in patient's with idiopathic polyhydramnios. Obstet Gynecol. 1992;79:234-239.

23. Barnhardt Y, Bar-Hava I, Divon MY. Is polyhydramnios in an ultrasonographically normal fetus an indication for genetic evaluation? Am J Obstet Gynecol. 1995; 173:1523-1527.

24. Elliott JP, Urig MA, Clewell WH. Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion syndrome. Obstet Gynecol. 1991;77:537-540.

25. Fisk NM, Talbert DG, Nicolini U, et al. Amniotic pressure in disorders of amniotic fluid volume. Obstet Gynecol.1990;76:210-214.

26. Moise KJ Jr. Polyhydramnios. Clin Obstet Gynecol. 1997;40:266-279.

27. Mari G, Moise KJ Jr, Deter RL, et al. Doppler assessment of the renal blood flow velocity waveform during indomethacin therapy for preterm labor and polyhydramnios. Obstet Gynecol. 1990;75:199-201.

28. Moise KJ Jr. Indomethacin as treatment for symptomatic polyhydramnios. Contemporary OB/GYN. 1995; 5:53-60.

29. Respondek M, Weil SR, Huhta JC. Fetal echocardiography during indomethacin treatment. Ultrasound Obstet Gynecol. 1995;5:86-89.

30. Norton ME, Merrill J, Cooper BA, et al. Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med. 1993;329:1602-1607.

31. Jones JM, Sbarra AJ, Dilillo L, et al. Indomethacin in severe twin-to-twin transfusion. Am J Perinatol. 1993; 10:24-26.

32. Kramer WB, Saade G, Ou CN , et al. Placental transfer of sulindac and its active sulfide metabolite in humans. Am J Obstet Gynecol. 1995;172:886-890.

33. Lampela ES, Nuutinen LH, Ala-Kokko TI, et al. Placental transfer of sulindac, sulindac sulfide, and indomethacin in a human placental perfusion model. Am J Obstet Gynecol. 1999;180:174-180.