Amniotic Fluid - 4 - Consequences of Decreased Amniotic Fluid

In the last three posts, we have reviewed basic aspects of amniotic fluid production and measurement and common causes of decreased amniotic fluid, or oligohydramnios. Now let’s look at reasons decreased amniotic fluid increases the risk for fetal (and newborn) complications and death. Complications related to decreased amniotic fluid depend on the underlying cause, the degree of the decrease, the timing during pregnancy, and the longevity during fetal development. First, let’s look at the worst case scenario – the baby that has no fluid (anhydramnios) from very early in the pregnancy on…

As mentioned in our last post, the most common conditions that lead to anhydramnios include absence of the fetal kidneys (bilateral renal agenesis), nonfunctional kidneys secondary to bilateral renal dysplasia (polycystic and multicystic kidneys), and complete bladder outlet obstruction (posterior urethral valves, or other anomalies associated with maldevelopment of the fetal bladder or urethra). In rare circumstances, complete bilateral obstruction of the ureters (ureteropelvic or ureterovesical junction obstruction) can also be found. Under these conditions, where the baby has essentially no amniotic fluid from late first trimester on, the outcome is uniformly LETHAL.

Interestingly, it is not the absence of kidney function that kills these babies – it is the fact that in the absence of amniotic fluid, the fetal lungs do not develop sufficiently to support breathing once they are actually born! Any of these conditions associated with early and sustained anhydramnios result in the same outcome secondary to pulmonary hypoplasia and insufficiency, and this has been labeled ‘Potter’s syndrome (or sequence)’ after the physician who first described it. Although, it is not known why the absence of fluid results in Potter’s syndrome, it is thought that the constant compression of the thorax contributes, that the production of fluid by the fetal lungs is suppressed, and even that some movement of amniotic fluid (fetal urine) into the lungs is essential for normal development of functional alveoli. Most babies who are born with Potter’s syndrome cannot even make any kind of respiratory effort at birth, and those that do, cannot get sufficient oxygen into their bodies to allow survival.

If you notice, I did not include premature and prolonged rupture of membranes (PPROM) in this category of inevitable lethal outcome. It is true that if PPROM occurs prior to 20-22 weeks, the baby is at risk for the full consequences of Potter’s syndrome, and the earlier the PPROM and the more severe the oligohydramnios, the greater the likelihood is that this will occur. Indeed, during my training, we were taught simply to offer such women induction of labor, not only because the fetal outcome was expected to be dismal but also because the risk of infection to the mother was so high. (Of course, when I trained, it was the rare baby born before 27 weeks that had any chance of survival anyway). But, I must admit, many patients I have had over the years have proven that old teaching to be incorrect, or at least not a certain death sentence for their babies. Some of these women will carry their babies to a point where there is potential viability (today, 23 weeks and beyond) and, though they are at risk for pulmonary hypoplasia, the degree of this is very difficult to predict and it may not be lethal. However, these babies may also be at increased risk for fetal deformations (particularly of the skeleton, thorax, and head) secondary to compression during development and in its most severe form, a condition termed the fetal akinesia/hypokinesia deformation sequence in which there are not only compression malformations but poor development of muscle, tendons, and enervation secondary to the lack of fetal movement in utero.

Although the above conditions are very serious, they are also all the least common complications related to oligohydramnios. Indeed, most babies will not develop decreased amniotic fluid until beyond 24 weeks gestation, so the issues related to pulmonary hypoplasia and major deformations are, fortunately, rare. The most common reasons for oligohydramnios in the latter part of pregnancy are PROM and placental insufficiency. In the case of the former, this can lead to the acute (sudden) decrease in amniotic fluid and in the latter, a more gradual reduction. Leaving infection out of the equation (as a common cause of PROM and associated with its own morbidity and mortality), the primary cause of fetal complications under these circumstances are related to umbilical cord compromise, and in the case of placental insufficiency, decreased fetal oxygenation (ultimately the cause with its own consequences, not the effect, of decreased amniotic fluid).

Normally, I tell patients that the umbilical cord is a lot like a fire hose. It is a ‘closed system’ and the blood contained within it is under some pressure. In other words, just because it is wrapped around the baby’s neck, or other body parts, or even tied into a knot, does not mean the baby is going to necessarily die as the result – in fact most don’t. At least one-third of all babies are born with the cord looped around the neck (nuchal cord) and most do just fine. However, the blood in the umbilical cord vessels is under differential ‘pressures’ depending on whether it is the poorly oxygenated arterial blood (higher pressure) coming from the baby to the placenta or the well-oxygenated venous blood (low pressure) coming back to the baby from the placenta. Obviously, when there is compression on the umbilical cord, the venous blood flow is much more likely to be impeded than the arterial blood flow.

Even if the blood in the umbilical cord is under pressure, in the presence of decreased or absent amniotic fluid it is possible for the baby to trap the cord in a position where blood flow is significantly reduced and the baby can be damaged or even die as the result of too little oxygen. I always worry about this most when there is sudden rupture of the membranes, or if the cord falls (prolapses) through the cervix, and, particularly, in women who are very heavy. It is also one of the causes of fetal morbidity and mortality in placental insufficiency sequences (accompanied by intrauterine growth restriction) because oftentimes in these circumstances, not only is the placenta poorly developed (and has less ‘reserve’), but the cord is often thinner and smaller and not endowed with adequate cushioning due to a reduction in the amount of Wharton’s jelly surrounding the blood vessels (normally two arteries and one vein) in the umbilical cord and, therefore, more likely to be significantly compromised when compressed.

Intermittent (and incomplete) umbilical cord compression can often be identified by distinct abnormalities of the fetal heart rate (FHR) tracing (most commonly, ‘variable decelerations’). These are quite common in labor, particularly after the membranes have ruptured either spontaneously or as the result of the provider’s intervention (artificial rupture of membranes, or AROM). FHR monitoring is, therefore, one means of identifying the baby ‘at risk’ for umbilical cord compromise. Most babies that have decreased fluid and normal placental function tolerate this type of FHR deceleration quite well, although they are still at increased risk for cesarean delivery if the FHR tracing begins to develop signs of ‘nonreassurance’ and spontaneous vaginal delivery is still remote. Since we seem to have spent a fair amount of time on this topic today, I will reserve further discussion on the evaluation and management of pregnancies with oligohydramnios to our next post…

Labels: amniotic fluid; AFV, anhydramnios, oligohydramnios, Potter's syndrome

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Amniotic Fluid - 3 - Oligohydramnios: Causes of Too Little Amniotic Fluid

Having discussed where amniotic fluid comes from and how we assess amniotic fluid volume, let’s address the most common amniotic fluid abnormality – too little fluid or oligohydramnios. There are 3 primary reasons why there is too little amniotic fluid: 1) rupture of membranes; 2) fetal abnormalities; 3) placental abnormalities.

Spontaneous rupture of membranes (SROM) can occur at any time in pregnancy. Most of the time, the membranes remain intact until the onset of labor, or just before labor, after the cervix has begun to change (efface and dilate). If membranes rupture prior to the onset of uterine contractions, it is called premature rupture of membranes or PROM, and if they are ruptured for more than 24 hours, prolonged premature rupture of membranes or PPROM. There are lots of things that can lead to rupture of membranes, but the ones we worry about most are infection, fetal anomalies that result in too much fluid (polyhydramnios or hydrammnios) and uterine overdistention, and cervical incompetence. The earlier in pregnancy that the membranes rupture, the greater the likelihood that it is associated with infection (with or without cervical incompetence) and this is usually infection with organisms that the mother carries in her body that get inside the uterus by ascending vaginal, blood-borne, or lymphatic transmission. However, the focus of this discussion is not to discuss SROM, but to remind readers that it is a very common cause of decreased amniotic fluid and when it occurs, the baby and the mother need to be evaluated carefully to look for causes. Since infection is often associated with PROM, that is usually what constitutes the greatest risk to the baby.

The least common, but often most serious, causes of decreased amniotic fluid are fetal abnormalities. If you recall in our first post on this subject, most of the amniotic fluid from early midtrimester on is fetal urine. Abnormalities of the fetal kidneys and urinary tract can lead to decreased urine output or the complete absence of amniotic fluid (anhydramnios) in the most severe cases. Babies can have the complete absence of both kidneys (bilateral renal agenesis), nonfunctioning kidneys associated with polycystic or multicystic renal dysplasia, or obstructive uropathies where there is blockage of urine at the urethra (usually the result of ‘posterior urethral valves’ in male children), or blockage of the ureters at various levels between the kidneys and the bladder (e.g., ureteropelvic junction (UPJ) or ureterovesical junction (UVJ)obstructions). An important point to note here is that if the baby only has ONE nonfunctioning kidney, or a blockage that affects only ONE side, the amniotic fluid is usually normal and the consequences of too little fluid for too long do not develop. However, if both kidneys are affected, this can lead to the complete absence of amniotic fluid and a condition that has been named “Potter’s sequence” which will be detailed in our next post on this subject.

Other causes of decreased fluid that may be transient (and therefore less serious) and/or reversible are congenital viral infections, such as cytomegalovirus (CMV) which has a predilection for the fetal kidneys, or conditions that affect maternal hydration. With regard to the latter, as we pointed out previously, if the mother becomes very dehydrated, or if she has a condition that severely decreases her plasma volume, the fluid around the baby, which depends so much on passive distribution from the mother across the placenta, can acutely decrease. Common conditions in which this is seen include: hyperemesis (too much vomiting), diarrhea, maternal sepsis, hemorrhage, placental abruption or previa, diabetic ketoacidosis, excessive fluid loss during fever or heat exposure, and severe preeclampsia. Oligohydramnios resulting from many of these conditions can be reversed or improved with expansion of the maternal plasma volume.

The last conditions I would like to discuss that lead to decreased amniotic fluid are those that result in decreased perfusion (blood flow) to the fetal kidneys. When it comes right down to it, the kidneys are ‘nonessential organs’ with regard to survival of the baby while it is inside its mother. For example, babies that have bilateral renal agenesis (no kidneys at all) can go all the way to term because the placenta and the mother serve as the means of removing ‘waste products’ from the baby. (They cannot survive after delivery for the reasons I will detail in my next post). Production of urine by the baby requires blood flow through the kidneys. When babies become dehydrated, or when they have to, preferentially, send blood to ‘essential organs’ such as the brain and the heart because they are not receiving enough oxygen and nutrients to support their whole bodies’ needs, their regulatory mechanisms of survival shut down blood flow to the kidneys, thereby, curtailing the production of urine.

This can occur as the result of primary fetal problems such as severe anemia associated with isoimmunization or parvovirus infections, or cardiac malformations or dysfunction from a variety of different causes. More commonly, however, this occurs as the result of abnormalities of placentation (small placentas and/or placentas that have not had normal invasion of the maternal spiral arterioles in the placental bed), wherein the babies have outgrown the capacity of the placenta to provide sufficient oxygen and/or nutrients. When ‘placental insufficiency’ occurs it is usually accompanied by intrauterine fetal growth restriction (IUGR). This usually means the baby is small for its gestational age, but there are occasions when this can occur in large babies, such as those seen in uncontrolled diabetic mothers, whose size also exceeds the capacity of the placenta to maintain their metabolic demands. When the amniotic fluid starts to go down in circumstances of placental insufficiency, this is also usually the result of ‘fetal blood flow redistribution’ away from the kidneys and to the essential organs necessary for survival.

Having discussed some of the more common causes of oligohydramnios, in our next installment of this series, we will address the evaluation, management, and consequences decreased amniotic fluid in pregnancy ….

Labels: amniotic fluid; AFV, IUGR, oligohydramnios, premature rupture of membranes

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Amniotic Fluid - 2 - Assessment of Amniotic Fluid Volume

We closed our last post with the comment that BOTH too much fluid (polyhydramnios, otherwise termed hydramnios) or too little fluid (oligohydramnios) are associated with fetal abnormalities and/or poor perinatal outcome. In fact, the greater the amniotic fluid abnormality, one way or the other, the greater the likelihood is of fetal complications or loss and, for that matter, maternal complications as well. The maternal complications are (usually) not related to the fluid abnormalities themselves (except in cases of severe polyhydramnios), but to the reasons the amniotic fluid volumes are abnormal to start with. That will become clearer as we proceed with these posts.

With the widespread use of ultrasound, we have come to use ‘semi-objective’ measures of amniotic fluid volume (AFV). Although what is “abnormal” has gone through various permutations over time, most practitioners assess AFV by one of two methods. The first method is to simply measure the depth of the single largest vertical pocket of fluid (free of umbilical cord and body parts) with the ultrasound transducer oriented perpendicular to the uterus and not just perpendicular to the abdominal wall and with a minimum of pressure on the transducer itself. If the single largest pocket is < 2 cm, the AFV is considered to be ‘decreased’ at anytime from midtrimester until term. If the single largest pocket is > 8 cm, the AFV is considered to be ‘increased’.

The second method that has gained perhaps the most popularity over time is the “amniotic fluid index (AFI).” This technique involves dividing the uterus into four ‘quadrants’ by imagining perpendicular lines running through the umbilicus of the mother, and then simply measuring the single deepest pocket of fluid in each quadrant and adding up the 4 results. At term, the mean AFI is 11.5 cm with 5th and 95th percentiles of 6.8 and 19.6 cm, respectively, and quite frankly, there is not much variation in those values from late midtrimester on. Oligohydramnios is then defined as an AFI < 5th percentile and polyhydramnios as > 95th percentile.

Either approach can be performed quickly and though the AFI technique would intuitively seem to give you a better total picture of AFV, in reality, there probably is no real difference in the reliability of the methods. Indeed, in experienced hands, subjective assessment of amniotic fluid by simply looking is probably just as good (may the lord of evidence-based medicine please not strike me down)! If there are only very small pockets of free fluid, the baby appears crowded, or in the most extreme cases, there is absolutely no fluid (severe oligohydramnios or anhydramnios) and the baby has gross pressure deformations of the head or extremities, or overlapping of the ribs, the diagnosis of too little fluid is readily apparent. In a similar vein, if the baby appears to be freely floating or turning and has no restriction of extremity extension, there is probably too much fluid. With all that said and done, since not everyone has ‘experienced hands’ and there is some beauty to numbers, we use the 4-quadrant AFI as our routine approach to the assessment of AFV.

In the next post in this series we will discuss specific conditions and complications associated with decreased amniotic fluid….

Labels: amniotic fluid; AFV, anhydramnios, hydramnios, oligohydramnios, polyhydramnios

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Amniotic Fluid - 1 - The Basics

We have readers with a wide range of backgrounds and medical sophistication. One of the things I have tried to do on this site is to provide information which appeals to readers across this spectrum. In some instances, we have discussed very basic information related to pregnancy and pregnancy complications, in others we have provided in depth analysis of subjects that may have more general interest, and in still others, we have focused on very narrow topics or even indulged in the arena of hypothesis.

While reviewing some of the subjects we have covered over the past 20 months to get some ideas for new posts, it dawned on me that we had never written about one of the most basic topics related to pregnancy that arises as a subject of discussion almost every day in my work for one reason or another - amniotic fluid. In today’s post, we will simply provide the basic background related to amniotic fluid production and clearance and in the posts that follow, we will discuss the significance (causes and effects) of abnormalities of amniotic fluid volume – too much and too little.

Most patients have no clue what amniotic fluid is and just take for granted that it is “just the bag of waters around the baby” that makes it easier to take pretty ultrasound pictures and gets “ruptured” by my doctor to help me labor faster at delivery. Indeed, when there is a clinical reason to discuss amniotic fluid, and I have the opportunity to tell them what it is and where it goes, they are often appalled or simply grossed out. Production and egress of amniotic fluid is a very dynamic process. It isn’t “just there.” Indeed it is estimated that more than 95% of amniotic fluid turns over on daily basis.

Very early in pregnancy, the fluid around the baby is the result of active transport of sodium and chloride across the fetal membranes juxtaposed to maternal tissues. As the salt moves, water follows passively. By the end of first trimester (between 8 and 11 weeks), however, an increasing proportion of amniotic fluid is the result of fetal urine production and later on production and expulsion from the fetal lungs. At the same time the fetal kidneys become the major source of amniotic fluid production, fetal swallowing and the lower gastrointestinal tract become the major means of removing that fluid from around the baby. In other words, the baby pees, then swallows it, then reabsorbs the fluid and passes it back (and forth) across the placenta to the mother. (It is this thought that tends to gross out the parents, so thank goodness the baby usually doesn’t poop much in utero). There are other sources of both fluid production and egress, but for the sake of simplicity, let’s begin our discussion with these basics. The amniotic fluid volume, then, is the sum of the inflows and outflows of the fluid in amniotic space around the baby.

At 16 weeks the amniotic fluid volume (AFV) is about 200 mL; AFV peaks at about 700 to 900 mL at 32-35 weeks in most normal pregnancies and then begins to gradually diminish. By term, the average baby produces about 700 to 900 mL/day of urine and 300 to 400 mL/day of fluid from the lungs. In many pregnancies, there is a dramatic drop in the amniotic fluid volume once the pregnancy gets beyond 42 weeks, corresponding to the time when, even in a ‘normal’ pregnancy, there is an increased risk of ‘unexplained’ fetal death in utero if a woman does not go into spontaneous labor.

In first trimester, the osmolality of amniotic fluid is comparable to that of blood (280 mOsm). However, from early on in pregnancy, the fetal kidneys are capable of retaining salt and other solutes, resulting in the production of urine that is ‘hypotonic’ (60-140 mOsm). This eventually results in a drop in the overall osmolality of the amniotic fluid as the pregnancy progresses. There is a tendency for the baby to lose salt across body surfaces exposed to the amniotic fluid, but usually the baby compensates for this much better than we do when we sit in a bathtub for a little too long and come out looking like a raisin! Fluid exchange between mother and baby occurs freely across the placenta. For this reason, acute changes in maternal hydration (reflected in her plasma osmolality) readily alter fetal hydration. Conditions during pregnancy that can affect maternal plasma volume (low and high), therefore, may be one of the factors that also influences amniotic fluid volume on a short- or long-term basis.

So, that is the basics of amniotic fluid production and overall volume. We actually understand very little about ‘regulation’ of amniotic fluid volume. What we do know, however, is that BOTH too much fluid (polyhydramnios or hydramnios) AND too little fluid (oligohydramnios) are associated with fetal abnormalities and/or poor perinatal outcome, and that’s where we will take this discussion in our next posts….

Labels: amniotic fluid; AFV

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Low PAPP-A in Presence of Low Risk for Fetal Aneuploidy

Below are comments from a woman aged 44 who is carrying a pregnancy conceived by in vitro fertilization (IVF) using a ‘donor egg’ from a 21 year old woman. She had combined first trimester screening done with composite results that were very reassuring with regard to risks for having a baby with trisomy 21 or trisomies 18 or 13, however she is concerned that the PAPP-A level in the screen was only 0.269 MoM (at about the 2.5 percentile). She is 44 years old, and that alone increases her risk for pregnancy complications related to abnormalities of placental growth and complications related to that during pregnancy and, indeed, low PAPP-A levels may reflect those abnormalities. However, I want to remind our readers at the outset that the ‘positive predictive value’ for low PAPP-A is not very good and means the chance of one of these events is higher with a low PAPP-A but does not mean that she will inevitably develop complications during her pregnancy…

• At Mon Apr 28, 02:45:00 AM 2008, Anonymous said…

Hi Dr T,
I am having trouble getting anyone to take my numbers seriously. The NT scan showed up a low PAPP-A result and the sonographer told me to ask my GP to watch this and to make sure my OB consultant knew about it. My GP wrote to the OB consultant and she has just told me this morning that "Don't worry - they are not concerned as the PAPP-A result is low which is good!" Even I know that this does not make sense. Can you please help me by giving your opinion as most info I have read on this amazing site seems to point towards a possible problem:

CRL:57.9mm
NT: 1.6mm
Placenta:posterior high
Free B-hcg: 0.956 MoM
PAPP-A: 0.269 MoM
Egg was IVF donor egg -maternal age 21 yrs.
I was 11weeks and 6 days when the scan was done.

I look forward to hearing from you.
Many thanks,
Jackie

• At Wed Apr 30, 05:05:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Jackie Apr 28: I wish I knew how old you are, what sort of medical problems you have, what was the cause of your infertility, and have you ever had any pregnancies (successful or not)? Barring that, it would be helpful to know what the calculated risk assessment result was for Down syndrome and trisomies 18/13 based on your test results.

Regardless, the low PAPP-A may not be good, but it may not be bad either! If you have read the posts I have written on this subject, and some of the comments from our readers and my responses, you will better appreciate why I seem to be talking out of both sides of my mouth. The reassuring components of your screen are the normal NT (nuchal translucency) and hCG measurements. With a "21 year old egg", I doubt your calculated risk for aneuploidy was very high. You are probably at modest risk for a small baby and the things that might go along with that, such as preterm labor, early delivery, preeclampsia, and cesarean section, but there might be other factors you have not told me about (or are not aware of) that might also put you at risk for these. My bet right now is that you will do fairly well with the pregnancy and nothing is wrong with your baby! Let us know how things turn out.
Dr T

• At Thu May 01, 03:16:00 AM 2008, Anonymous said…

Hi again Dr T,
I am so grateful for your reply and apologies for omitting some of the info. I am 44 years old with no medical problems except a fibroid which has appeared with this pregnancy. The infertility was unexplained, save for mild endometriosis. I had one pregnancy last year (natural) which ended after just 6 weeks with no explanation. I have had 2 previous rounds of IVF - the first produced 4 follicles and 2 embryos were implanted but did not take. The second produced no follicles.

The adjusted risk for Downs was 1:1804 and for Trisomy 18+13 was 1:18628. I was advised that no amniocentesis or CVS (chorionic villus sampling) would be necessary. My main concern is the IUGR/stillbirth scenario which seems to go hand in hand with a low PAPP-A result. Do you imagine that my doctors would keep a closer eye on me - in your opinion what should I be pushing for at my 20 week scan? Will the AFP result throw anything in to the mix as I am yet to receive that?
Thank you again.
Jackie

• At Thu May 01, 10:49:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Hello again Jackie. When the PAPP-A is low, the women at greatest risk for complications are those that also have a placenta that is smaller than normal and/or did not have normal growth into the lining of the uterus (specifically into the uterine spiral arterioles). The MSAFP (maternal serum alphafetoprotein test at 16 weeks can sometimes provide an insight to that as a possibility. If the AFP is abnormally high, and there are no apparent abnormalities (such as a neural tube or abdominal wall defect) of the baby to be seen, then that "false positive" result may actually reflect an underlying placental problem (that may not manifest itself as a problem such as fetal growth restriction or maternal preeclampsia until later in the pregnancy).

The other procedure we use that can also anticipate risks down the line is Doppler flow velocimetry. This is an ultrasound technique that can help us to detect degrees of 'resistance' to blood flow. If you and/or the baby are found to have trouble pushing blood through the placenta by virtue of increased resistance in the uterine or umbilical arteries, respectively, this can be another reason to keep a closer eye on the baby's growth, development and overall well-being. None of these will accurately predict outcome, but if they are abnormal, can justify more intensive antepartum fetal surveillance so that chances of delivering a healthy baby, regardless of the gestational age, are improved. So, do not panic at this point! Again, thanks for your questions and let us know how things turn out!
Dr T

COMMENT:
As we have pointed out before, first trimester screening for aneuploidy can have some benefits for detecting potential complications of pregnancy other than certain chromosomal abnormalities. Our reader reports that her ‘composite’ first trimester screening result was reassuring with regard to risk for a chromosomally abnormal baby, but one of the maternal serum markers, PAPP-A (pregnancy-associated plasma protein-A), was “low” at 0.269 MoM (multiples of the median).

PAPP-A is produced by the placental trophoblasts, especially, by the extravillous cytotrophoblasts (Handschuh, et al., Placenta 2006;27 suppl A:S127-34). It is a ‘protease’ for insulin-like growth factor (IGF) binding proteins 4 and 5 (Boldt and Conover. Growth Horm IGF Res. 207;17:10-18). It has the ability to help release IGF from these binding proteins so that it is free to interact with its cell receptor (Laursen, et al., Mol Endocrinol 2007;21:1246-57). IGF is thought to play an important role in trophoblast invasion and hence the early development and vascularization of the placenta and the placental bed. These early events in formation of the placenta are critical to pregnancy outcome and, when abnormal, are associated with miscarriage, intrauterine growth restriction (IUGR) of the baby, pregnancy-induced hypertensive disorders, fetal death in utero, premature delivery, and even cesarean section for indications of fetal or maternal compromise. It has been postulated that low levels of PAPP-A, resulting in less release of IGF, could be a pathway by which placentation abnormalities occur that culminate in these poor pregnancy outcomes.

Several studies confirm the association of ‘pregnancy complications’ with low levels of PAPP-A. In the First and Second Trimester Evaluation of Risk (FASTER) trial, it was found that women with PAPP-A at or below the 5th percentile “were significantly more likely to experience fetal loss at less than or equal to 24 weeks, low birth weight, preeclampsia, gestational hypertension, preterm birth (P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption (P < .02)” (Dugoff, et al., Am J Obstet Gynecol 2004; 191:1446-61). Spencer and colleagues (Ultrasound Obstet Gynecol 2006;28:637-43) evaluated first trimester markers in 54,722 chromosomally normal singleton pregnancies. They found that the odds for fetal loss at anytime in pregnancy was about three-fold that of ‘normals when the PAPP-A levels were at or below the 5th percentile (0.415 MoM).

Labels: aneuploidy screening in first trimester, Doppler flow velocimetry, PAPP-A

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