Antenatal and Intrapartum Care of the High-Risk Infant

Prenatal Genetic Testing for Trisomy 21

Caring for a child or adult with special needs has a significant impact on a couple and family. Down syndrome is the most common chromosomal abnormality causing mental disability in the United States. In addition to cognitive deficits, these children are also at risk for congenital heart disease, duodenal atresia, urinary tract malformations, epilepsy, and leukemia. Prenatal testing for chromosomal abnormalities is a matter of weighing the risks of the genetic condition in question with the ultimate risks of the tests available to identify that abnormality. This should include the risks of a false-negative result in an affected pregnancy and the false-positive result in the unaffected pregnancy and the possible riskier diagnostic tests that may follow. Since the late 2000s, the ability to more effectively and safely diagnose Down syndrome has improved.

Prenatal testing for Down syndrome has moved away from the traditional invasive diagnostic testing based on age alone. Presently, a combination of maternal blood tests and US screening provides women with choices beyond routine chorionic villus sampling (CVS) or amniocentesis. Optimally, this prenatal screening should minimize the number of women identified as screen positive while maximizing the overall detection rate. These screening tests therefore require a high sensitivity and a low false-positive rate. The improvements in testing have achieved this and ultimately reduced the number of invasive tests performed and, in turn, decreased the rate of procedure-related losses. Historically, the first screening tests used maternal age as a cutoff for risk assessment because the prevalence of trisomy 21 rises with age. Women aged 35 and above were eligible for screening based on a cost-benefit analysis and an attempt to match the risk of an affected fetus with a procedure-related loss. Screening based on this parameter of advanced maternal age (AMA) alone had a detection rate of about 30%, with a false-positive rate of 5% when implemented in the 1970s.

From 1974 to 2002, the mean age of women giving birth in the United States increased from 24.4 to 27.4 years, and the percentage of women aged 35 years and older at birth increased from 4.7% to 13.8%. Using AMA as the main parameter became less efficacious. In 1984, the association between aneuploidy and low levels of maternal serum alpha-fetoprotein (MS-AFP) was reported. In 1987, the association between high maternal serum human chorionic gonadotropin (hCG) value and a low conjugated estriol level in Down syndrome pregnancies was reported. In 1988, this information was first integrated and called the “triple screen test.” Combining MS-AFP, hCG, and unconjugated estriol values with maternal age risk and performing it between 15 and 22 weeks’ gestation doubled the age-related detection rate to 60% and maintained the false-positive rate at 5%. The test is considered positive when the result, stated as an estimate of risk, is above the set cutoff range. This is usually about 1:270 and based on the second-trimester age-related risk of a 35-year-old woman. In 1996, the “quad screen” was created when the level of inhibin-A was added to the triple screen. This test has a detection rate of 76% and a false-positive rate that remains at 5%.

Since the 1980s, the addition of ultrasonography to the practice of obstetrics has allowed for the detection of significant fetal abnormalities prior to delivery ( Fig. 2.1 ). About 20% to 27% of second-trimester fetuses with Down syndrome have a major anatomic abnormality. Over time, sonographic markers were identified that, when present, increase the likelihood that a chromosomal abnormality may exist. The risk increases as the number of markers increases. Sonographic markers are seen in 50% to 80% of fetuses with Down syndrome. The most common markers are cardiac defects, increased nuchal fold thickness, hyperechoic bowel, shortened extremities, and renal pyelectasis. When a second-trimester US is performed to search for these markers, it is called a “genetic sonogram.” The overall sensitivity of this US is 70% to 85%.

Nuchal translucency is a standard US technique and is most accurately measured in skilled hands between 10 to 14 weeks’ gestation ( Figs. 2.2 and 2.3 ). There is a direct correlation between an increased measurement and a risk for Down syndrome, other aneuploidy, and major structural malformations. In fact, a very large nuchal translucency suggests a very high risk for aneuploidy. Down syndrome, trisomy 18, and Turner syndrome are the most likely chromosomal abnormalities, and cardiac defects are the most likely malformations.

Serum genetic screening and genetic sonography evolved into a combined testing approach. With this method, the sensitivity of Down syndrome screening increased, whereas the false-positive rate decreased. The rationale involves modifying the prior maternal age risk up or down. If the pattern seen is similar to the pattern in a Down syndrome pregnancy, then the risk is increased; if it is the opposite, then it is decreased. The magnitude of this difference is expressed in multiples of the median (MoM), and it determines how much the risk is modified. For sonographic markers, the magnitude of these differences is measured by a likelihood ratio (LR = sensitivity/false-positive rate) that is then multiplied by the a priori risk.

This next phase of screening became the “first-trimester screening” protocol. The US component involves the sonographic measurement of the nuchal translucency. If this measurement is increased for the gestational age, it can indicate an affected fetus. This is an operator-dependent measurement, but it has demonstrated a 62% to 92% detection rate. The serum markers that are measured are maternal serum beta-hCG and maternal serum pregnancy-associated plasma protein A (PAPP-A). In the first trimester, pregnancies in which the fetus has Down syndrome have higher levels of hCG and lower levels of PAPP-A than do unaffected pregnancies. This combination of maternal age, nuchal translucency, hCG, and PAPP-A is now the standard first-trimester screening and is called the “first-trimester combined test.” It has a detection rate of 85% and a false-positive rate of 5%. This is better than the quadruple screen detection rate of 80% and false-positive rate of 5%, and therefore it became the recommended screen for women who presented early in pregnancy.

It makes sense to offer Down syndrome screening as early in pregnancy as possible. Performed between 11 and 13 weeks’ gestation, the first-trimester screening combined test provides for as early an evaluation and diagnosis as possible for fetal abnormalities. It also provides for maximum decision-making time and adjustment, privacy, and safer termination options if desired. One of the issues with such sophisticated screening protocols is the timing and availability of such methods. The ACOG recommends that all women be offered screening before 20 weeks’ gestation, and all women should have an option of invasive testing regardless of age. They also recommend that prenatal fetal karyotyping should be offered to women of any age with a history of another pregnancy with trisomy 21 or other aneuploidy, at least one major or two minor anomalies in the present pregnancy, or a personal or partner history of translocation, inversion, or aneuploidy.

The impact of prenatal screening is significant. During this age of first-trimester screening, the number of amniocentesis and CVS procedures performed has dropped. In areas where Down syndrome screening tests have been implemented, there has been an increase in the detection of affected fetuses and a drop in the number of live births with Down syndrome.

Major advances in aneuploidy screening have been made. Noninvasive prenatal screening (NIPS) evaluates cell-free DNA from maternal blood to screen for a variety of fetal conditions. The fetal component of cell-free DNA in maternal blood is mainly from apoptotic placental cells. Not only does cell-free DNA screen for aneuploidies, but it also can determine fetal sex, an Rh-positive fetus, and some genetic abnormalities. The test is done as early as 10 weeks’ gestation and has the highest detection rate for Down syndrome at 98%. Advantages of NIPS are the ease and accuracy of the test. The main disadvantage is that it is still a screening test, and many women may choose to have it done over more invasive testing, leading to a delay in diagnosis and management of fetal aneuploidy.

Prenatal Screening for Neural Tube Defects

The incidence of NTDs in the United States is considered to be highly variable because it depends on geographic factors and ethnic background. Typically seen in 1 in 1000 pregnancies, they are considered to be the second most prevalent congenital anomaly in the United States, with only cardiac anomalies occurring more often. It has been recommended by ACOG that screening for NTDs should be offered to all pregnant women. The American College of Medical Genetics also recommends screening using the MS-AFP and/or ultrasonography between 15 and 20 weeks’ gestation.

The majority of NTDs are isolated malformations caused by multiple factors such as folic acid deficiency, drug exposure, excessive vitamin A intake, maternal diabetes mellitus, maternal hyperthermia, and obesity. A genetic origin is also suggested by the fact that a high concordance rate is found in monozygotic twins. NTDs are also more common in first-degree relatives and are seen more often in females than males. Family history also supports a genetic mode of transmission. The recurrence risk for NTDs is about 2% to 4% when there is one affected sibling and as high as 10% when there are two affected siblings. There is also some evidence that NTDs are associated with the genetic variance seen in the homocysteine pathways ( MTHFR gene) and the VANGL1 gene. There is also a high prevalence of other karyotypic abnormalities, and trisomy 18 is typically the most common aneuploidy found.

In the 1970s and through the 1980s, maternal serum screening programs were instituted and combined with preconception supplementation with folic acid. In the 1990s, folic acid food fortification was implemented. During this time, screening protocols were also instituted, and initially they involved just the MS-AFP and amniocentesis for abnormal results and then went on to include sonography. Where these methods were employed, a decrease in the prevalence of NTDs was seen—largely due to the prevention of preconceptual folic acid deficiency in women.

Screening for open NTDs typically involves the MS-AFP, which is most optimally drawn between 16 and 18 weeks’ gestation. It is made by the fetal yolk sac, gastrointestinal tract, and liver, and is a fetal-specific globulin. It is similar to albumin and can be found in the maternal serum, amniotic fluid (from fetal urine), and fetal plasma. It is found in much lower concentrations in the maternal serum than in the amniotic fluid or fetal plasma. The primary intent is to detect open spina bifida and anencephaly, but when concentrations are abnormal, it can also suggest the presence of other nonneural abnormalities such as ventral wall defects.

For each gestational week, these results are expressed as MoM. A value above 2.0 to 2.5 MoM is considered abnormal. Some characteristics can significantly affect the interpretation of the results. A screen performed before 15 weeks and after 20 weeks’ gestation will falsely raise or lower the MoM. Maternal weight affects the results because the AFP is diluted in the larger blood volume of obese women. Women with diabetes mellitus have an increased risk of NTDs, and so their threshold value has to be adjusted to give a more accurate sensitivity. The presence of other fetal anomalies increases the level of the MS-AFP. The MoM level also has to be adjusted in pregnancies with multiple gestations because the MS-AFP level is proportional to the number of fetuses. Race can affect the results of the MS-AFP: African American women have a baseline level that is 10% higher than that of non–African American women. Finally, MS-AFP cannot be interpreted in the face of fetal death; therefore it cannot be used as a screening method when there is a nonviable fetus present in a multiple gestation.

US can potentially detect more NTDs than MS-AFP. Detection rates depend on the type of anomaly and the trimester during which it is used. One large cohort study found that US detected 100% of NTDs and that MS-AFP was not as useful as previously believed. Anencephaly and encephalocele have detection rates between 80% and 90% in the first trimester, whereas detection rates of over 90% for spina bifida are not seen until the second trimester. Although the vast majority of NTDs can be seen on US and the sensitivity of the US evaluation is high, the ultimate diagnosis depends on the position of the fetus, the size and location of the defect, the maternal body habitus, and the skill of the ultrasonographer.

Women who have a screen-positive pregnancy will be counseled to undergo an US to document accurate gestational age, fetal viability, and possible presence of multiple gestation. A detailed anatomic survey of the fetus will also be performed. The use of amniocentesis may also be employed if there is some discrepancy found on US that does not explain the abnormal MS-AFP. Elevations in both amniotic fluid AFP and amniotic fluid acetylcholinesterase suggests an open NTD with almost 96% accuracy. There is some conflict today regarding the use of amniocentesis, and some experts believe that US alone should be used, given its high detection rate, absent procedure loss rate, and cost-savings advantage. ACOG now recommends a second-trimester US between 18–22 weeks’ gestation to screen for anomalies, including NTDs. First-trimester US may detect some NTDs, but the rate of detection is much lower than with second-trimester ultrasonography. MRI of the fetus can also be used when there is some factor that is interfering with US diagnosis of the defect. This additional modality can be of great significance when planning for potential fetal or neonatal surgery, route of delivery, and overall counseling of the parents.

Fetal surgery for myelomeningocele was studied in a randomized trial comparing outcomes of in utero repair to standard postnatal repair. The trial was stopped early because of the improvements seen with prenatal surgery. A composite outcome of fetal or neonatal death or the need for placement of cerebrospinal fluid shunt by the age of 12 months was seen in 98% of the postnatal surgery group versus 68% of the infants in the prenatal surgery group. Prenatal surgery, however, was associated with more preterm delivery as well as uterine dehiscence at delivery.

Formal Maternal Monitoring of Fetal Activity

Fetal movement perception is routinely taught in obstetrical practice as an expression of fetal well-being in utero, and its counting is purported to be a simple method of fetal oxygenation monitoring. With a goal of decreasing the stillbirth rate near term, there has been an increased tendency to use fetal movements as an indicator of fetal well-being. It is monitored by maternal recording of perceived activity or using pressure-sensitive electromechanical devices and real-time US. A diagnosis of decreased fetal movement is a qualitative maternal perception of reduced normally perceived fetal movement. There is no consensus regarding a perfect definition, nor is there consensus regarding the most accurate method for counting. Whereas evidence of an active or vigorous fetus is reassuring, an inactive fetus is not necessarily an ominous finding and may merely reflect fetal state (fetal activity is reduced during quiet sleep, by certain drugs including alcohol and barbiturates, and by cigarette smoking). Three commonly used methods for fetal kick counts include perception of at least 10 fetal movements during 12 hours of normal maternal activity, perception of at least 10 fetal movements over 2 hours when the mother is at rest and concentrating on counting, and perception of at least four fetal movements in 1 hour when the mother is at rest and focused on counting. Fetal movement does decrease with hypoxemia, but there are conflicting data regarding its use to prevent stillbirth. Nonetheless, maternal perceived fetal inactivity requires prompt reassessment, including real-time US or electronic FHR monitoring.

Antepartum Fetal Heart Rate Monitoring

Antepartum electronic monitoring of the FHR has provided a useful approach to fetal evaluation ( Table 2.5 ). It essentially involves the identification of two FHR patterns: nonreassuring (associated with adverse outcomes) and reassuring (associated with fetal well-being). These patterns are interpreted in the context of gestational age, maternal conditions, and fetal conditions, and compared to any prior evaluations. Electronic fetal monitors use a small Doppler US device that is placed on the maternal abdomen. It focuses a small beam on the fetal heart, and the monitor interprets these signals of the heartbeat wave and reflects its peak in a continuously recording graphic form. This pattern is then evaluated for the presence and absence of certain components that help identify fetal well-being.

Antepartum testing is performed to observe pregnancies with an increased risk of fetal death or neurologic consequences ( Box 2.2 ). The NST is the most commonly used method. It is performed at daily or weekly intervals, but there are no high-quality data regarding the optimal interval of testing. Frequency is based on clinical judgment, and the presence of a reassuring test only indicates that there is no fetal hypoxemia at that time. It is commonly understood that a reactive NST assures fetal well-being for 7 days, but this is not proven. The management of a nonreactive NST depends on the gestational age and clinical context. The false-positive rate of an NST may be as high as 50% to 60%, so additional testing such as vibroacoustic stimulation, BPP, and possibly CST are useful adjuncts.

The oxytocin challenge test, or CST, records the responsiveness of the FHR to the stress of induced uterine contractions and thereby attempts to assess the functional reserve of the placenta. A negative CST (no FHR decelerations in response to adequate uterine contractions) gives reassurance that the fetus is not in immediate jeopardy. The CST evaluates uteroplacental function and was traditionally performed by initiating uterine contractions with oxytocin (pitocin). Because continuous supervision and an electronic pump is required for regulated oxytocin infusion and because of the invasiveness of intravenous infusion, attempts have been made to induce uterine contractions with nipple stimulation either by automanipulation or with warm compresses. Nipple stimulation has a variable success rate and, because of inability to regulate the contractions, as well as concerns raised by the observation of uterine hyperstimulation accompanied by FHR decelerations, it has not gained wide acceptance. Nonetheless, breast stimulation provides an alternative, cheap technique for initiating uterine contractions and evaluating placental reserve. Similar information may be obtained by evaluating the response of the FHR to spontaneous uterine contractions and perhaps also from the resting heart rate patterns without contractions. Because the CST requires the presence of contractions and has the major drawback of a high false-positive rate, its use has diminished with the better understanding of the NST and the use of the BPP and Doppler velocimetry.

As understanding of the NST evolved, it was noted that the absence of accelerations on the FHR tracing was associated with poor fetal outcomes, and the presence of two or more accelerations on a CST was associated with a negative CST. Although the false-negative and false-positive rates are higher for an NST than a CST, it is more easily used and therefore is the initial method of choice for first-line antenatal testing.

The modified NST has become the initial testing scheme of choice. The modified NST comprises vibroacoustic stimulation, initiated if no acceleration is noted within 5 minutes during the standard NST. Because reactivity is defined by two accelerations within 10 minutes, the sound is repeated if 9 minutes have elapsed since the first acceleration. Vibroacoustic stimulation, using devices emitting sound levels of approximately 80 dB at a frequency of 80 Hz, results in FHR acceleration and reduces the rate of falsely worrisome NSTs. Thus, the specificity of the NST may be improved by adding sound stimulation.

Amniotic Fluid Volume

The amniotic fluid volume (AFV) is measured via US using the value of the amniotic fluid index (AFI). This is the sum of the measured vertical amniotic fluid pockets in each quadrant of the uterus that does not contain the umbilical cord. The value can be associated with a number of potential complications depending on whether it is too high (polyhydramnios) or too low (oligohydramnios), although set recommendations for monitoring are not established. When found, alterations in AFV can suggest the presence of premature rupture of membranes, fetal congenital and chromosomal anomalies, fetal growth restriction, and the potential for adverse perinatal outcomes such as intrauterine fetal demise. Pregnancies that are at risk for AFV abnormalities where surveillance may be indicated include those with such conditions as preterm premature rupture of membranes (PPROM), hypertension, certain fetal congenital abnormalities, maternal infection conditions, diabetes, IUGR, and postterm pregnancies.

Fetal Biophysical Profile

Five components—the NST, fetal movements of flexion and extension, fetal breathing movements, fetal tone, and AFV—constitute the fetal BPP ( Table 2.6 ). It is performed over a 30-minute period, and the presence of each component is assigned a score of 2 points for a maximum of 10 of 10. A normal score is considered to be 8 of 10 with a nonreactive NST or 8 of 8 without the NST. Equivocal is 6 of 10, and abnormal is ≤4 of 10. This test assesses the presence of acute hypoxia (changes in the NST, fetal breathing, body movements) and chronic hypoxia (decreased AFV). A modified BPP refers to an NST and an AFI. The risk of developing fetal asphyxia within the next 7 days is about 1 in 1000 with a score of 8 to 10 of 10 (when the AFI is normal). The false-negative rate is 0.4 to 0.6 per 1000. A normal fetal BPP appears to indicate intact CNS mechanisms, whereas factors depressing the fetal CNS reduce or abolish fetal activities. Thus, hypoxemia decreases fetal breathing and, with acidemia, reduces body movements. The BPP offers a broader approach to fetal well-being than does the NST but still allows for a noninvasive, easily learned and performed method for predicting fetal jeopardy. Guidelines for implementation parallel that for other antenatal fetal assessment techniques, and so the BPP is usually initiated at 32 to 34 weeks’ gestation for most pregnancies at risk for stillbirth.

Doppler Velocimetry

Doppler velocimetry has been used to assess the fetoplacental circulation since 1978, but still has a limited role in fetal evaluation. Because the placental bed is characterized by low resistance and high flow, the umbilical artery maintains flow throughout diastole. Diastolic flow steadily increases from 16 weeks’ gestation to term. A decrease in diastolic flow, indicated by an elevated systolic-to-diastolic ratio, reflects an increase in downstream placental resistance. A normal waveform is considered reassuring and presumes normal fetal oxygenation. Elevated systolic-to-diastolic ratios are best interpreted in conjunction with NSTs and the fetal BPP. The information gathered from the study of Doppler waveform patterns depends on the vessel being studied. Measurement of these velocities in the maternal and fetal vessels suggests information about blood flow through the placenta and the fetal response to any negative changes, and so any challenge to the fetoplacental circulation can ultimately result over time in a compromise of the vascular tree. These indices in the umbilical artery will rise when 60% to 70% of the vascular tree has been altered. The ultimate development of absent or reversed diastolic flow (defined as the absence or reversal of end-diastolic frequencies before the next systolic upstroke) in the umbilical artery is regarded as an ominous finding and is associated with fetal hypoxia and fetal acidosis with subsequent adverse perinatal outcome. Umbilical artery Doppler evaluation is most useful in monitoring the pregnancy that is associated with maternal disease (hypertension or diabetes), uteroplacental insufficiency, and fetal IUGR, and it is not supported in the routine surveillance in other settings.

When a fetus is compromised, the systemic blood flow is redistributed to the brain. Doppler assessment of the fetal middle cerebral artery is presently the best tool for evaluating for the presence of fetal anemia in the at-risk pregnancy. It has all but replaced the use of percutaneous fetal umbilical blood sampling (cordocentesis or percutaneous umbilical cord blood sampling [PUBS]) in the evaluation of pregnancies involving Rh isoimmunization and other causes of severe fetal anemia, such as parvovirus-induced hydrops fetalis or hemolytic anemia.

Fetal Blood Sampling

In the past, fetal blood sampling was indicated for rapid karyotyping and diagnosis of the heritable disorders of the fetus, diagnosis of fetal infection, and determination and treatment of fetal Rh(D) disease and severe anemia. Historically, PUBS, or cordocentesis, provided direct access to the fetal circulation for both diagnostic and therapeutic purposes. Presently, the procedures of CVS and amniocentesis allow for the acquisition of the same information at an earlier time and with lower risk to the fetus. Fetal diagnostic tests for karyotype can be performed on the amniocytes or chorionic villi. Fetal involvement in maternal infections, such as parvovirus B19, can also be determined through identification of infection in amniotic fluid, fetal ascites, or pleural fluid, and Doppler of the middle cerebral artery is used to evaluate and follow subsequent fetal anemia. Inherited coagulopathies, hemoglobinopathies, and platelet disorders can also be identified through CVS and amniocentesis, but the immunologic platelet disorders such as idiopathic thrombocytopenia purpura and alloimmune thrombocytopenia may benefit from fetal blood sampling with antepartum PUBS and during labor through fetal scalp sampling. Preparations for and ability to transfuse must be available. Suspected fetal thyroid dysfunction remains an area where fetal blood sampling by PUBS may be necessary and plays a critical role in the diagnosis and management of the disease.

Chorionic Villus Sampling and Amniocentesis

CVS is a method of prenatal diagnosis of genetic abnormalities that can be used during the first trimester of pregnancy. Small samples of placenta are obtained for genetic analysis. It can be performed either transcervically or transabdominally. The major indication for CVS is an increased risk for fetal aneuploidies owing to AMA, family history, and abnormal first-trimester screening for Down syndrome. It can also be used to detect hemoglobinopathies. Amniocentesis is a transabdominal technique by which amniotic fluid is withdrawn so it may be assessed. The most common indications include prenatal genetic analysis and assessment for intrauterine infection and fetal lung maturity. It may also be used to evaluate for other fetal conditions associated with hemoglobinopathies, blood and platelet disorders, NTDs, twin-to-twin transfusion, and polyhydramnios. It is usually performed under US guidance and has a low rate of direct fetal injury from placement of the needle.

Procedure-related loss rates for CVS have been identified as 0.2% in a recent metaanalysis. The pregnancy loss rate associated with amniocentesis has been reported to be from 1 in 300 to 1 in 750. Although the safety and efficacy of both procedures has been established, CVS is considered to be the method of choice for first-trimester evaluation because it has a lower risk of pregnancy-related loss than does amniocentesis before 15 weeks’ gestation. Second-trimester amniocentesis is associated with the lowest risk of pregnancy loss.

Assessing Fetal Maturity

Because respiratory distress syndrome (RDS) is a frequent consequence of premature birth, both spontaneous and iatrogenic, and is also a major component of neonatal morbidity and mortality in many high-risk situations, it is critical that an antenatal assessment of pulmonary status be performed when indicated. The main value of fetal lung maturity testing is predicting the absence of RDS. It is not typically performed prior to 32 weeks’ gestation because physiologically the fetus is likely to have not yet matured. Fetal pulmonary maturity should be confirmed in pregnancies scheduled for delivery before 39 weeks’ gestation unless the following criteria can be satisfied: US measurement at less than 20 weeks of gestation that supports gestational age of 39 weeks or greater, FHT by Doppler ultrasonography have been present for 30 weeks, or it has been 36 weeks since a positive serum or urine pregnancy test. If any of these confirm a gestational age of 39 weeks, amniocentesis can be waived for delivery. Lung maturity does not need to be performed when delivery is mandated for fetal or maternal indications.

Historically, the introduction of amniocentesis for study of amniotic fluid and Rh-immunized women paved the way for development of the battery of tests currently available to assess fetal maturity. The initial methods developed were based on amniotic fluid levels of creatinine, bilirubin, and fetal fat cells, and these provided a good correlation with fetal size and gestational age. They were, however, inadequate predictors of fetal pulmonary maturity.

Amniocentesis to assess fetal pulmonary maturity is the currently accepted technique. Fetal lung secretions can be found in amniotic fluid. Evaluation of the amniotic fluid tests either for the components of the fetal pulmonary surfactant (biochemical tests) or for the surface-active effects of these phospholipids (biophysical tests). The lecithin-to-sphingomyelin ratio (L:S) and the presence of phosphatidylglycerol are biochemical tests, whereas the fluorescence polarization or the surfactant-to-albumin ratio (TDx-FLM II) is a biophysical test. Lamellar body counts can also be used. No test has been shown to be more superior to the other at predicting RDS, and each has its own defined level of risk. The predictive values of RDS vary with gestational age and with the population.

The risk of RDS is least when the L:S ratio is greater than 2.0. However, this does not preclude the development of RDS in certain circumstances (e.g., infant of a diabetic mother or erythroblastosis). Given the physiology of fetal lung maturity, the presence of phosphatidylglycerol is a good indication of advanced maturity and therefore a correlated lessened risk of RDS with fewer false-negative results. Phosphatidylglycerol can be measured by rapid tests, is not influenced by blood or vaginal secretion, and can be sampled from a vaginal pool of fluid. The surfactant-to-albumin ratio is a true direct measurement of surfactant concentration. Levels greater than 55 mg of surfactant per gram of albumin correlate well with maturity, whereas those less than 40 mg are considered immature. Lamellar body count, with a size similar to platelets, is a direct measurement of surfactant production by type I pneumocytes. Given their size, a standard hematology counter can be used for their measurement; values of greater than 50,000/μL indicate maturity. The negative predictive value of these tests is high so that when one result is positive, the development of RDS is unlikely.