Identification of the Pregnancy at Risk
The goal of prenatal care is to ensure optimal outcomes for both baby and mother. Prenatal care involves a series of assessments over time as well as education and counseling that help guide the interventions that may be offered. A significant part of the process involves identifying a pregnancy as high risk. Early and accurate establishment of gestational age, identification of the patient at risk for complications, anticipation of complications, and the timely implementation of screening, diagnosis, and treatment help to achieve these goals. The distinction between a high-risk versus a low-risk pregnancy and/or mother gives the provider the opportunity to potentially intervene prior to the advent of adverse outcomes. This chapter will discuss the identification of the high-risk pregnancy focusing on some of the more commonly encountered fetal and maternal conditions.
Many of the principal determinants of perinatal morbidity and mortality have been delineated. Included among these are maternal age, race, socioeconomic status, nutritional status, past obstetric history, family history, associated medical illness, and current pregnancy problems. Ideally, the process of risk identification is established prior to conception because it is the time when counseling for and against certain behaviors, foods and nutritional supplements, medications, work and environmental risks is likely to have the most beneficial outcome. Preparations can be made for certain medical and obstetrical conditions long before untoward effects have occurred. Therefore, any such assessment should include a detailed history that involves elements of personal and demographic information, personal and family medical, psychiatric and genetic histories, past obstetrical, gynecological, menstrual and surgical histories, current pregnancy history, domestic violence history, and drug and tobacco use history. The care provider should also assess for any barriers to care and whether the patient has any social concerns that would be better evaluated and managed by someone with social services expertise.
Accurate estimation of date of delivery (EDD) is crucial to the timing of interventions, monitoring fetal growth and timing of delivery, as well as for overall management. This is usually calculated from the date of a known last menstrual period (LMP) and can be confirmed by ultrasound if dating is uncertain due to irregular menses or if conception occurred on hormonal contraception. A standard panel of tests is ordered for all pregnant women at their first prenatal visit. This work-up is modified based on the woman’s risk profile. What constitutes optimal prenatal care and performed by whom and how often may still be up for debate. Screening and treatment of asymptomatic bacteriuria, group B beta-hemolytic Streptococcus (GBS), and sexually transmitted diseases for at-risk women to prevent the consequences of horizontal and vertical transmission is indicated. Screening should also be offered for fetal structural and chromosomal abnormalities and women who are Rh (D)-negative should receive anti (D)-immune globulin to prevent alloimmunization and reduce the risk of hemolytic disease of the newborn. Screening for malpresentation of the fetus, as well as development of preeclampsia in the mother, is also likely to have a great impact on pregnancy outcomes.
In the United States, about 12% to 13% of all live births are premature and about 2% are born at less than 32 weeks. Approximately 50% of these births are the result of spontaneous preterm labor, 30% from preterm rupture of membranes, and 20% from induced delivery secondary to maternal or fetal indications. Prematurity remains a significant perinatal problem, because prematurity along with the associated low birth weight is the most significant contributor to infant mortality. Mortality increases with both decreasing gestational age and birth weight. Additional causes of mortality include congenital anomalies, as well as delivering in a hospital with a lower level of resources and experience in providing such complex neonatal care. Improvements in obstetric and neonatal care, including surfactant, antenatal steroids, and maternal transport to an appropriate delivery facility capable of caring for high-risk neonates have decreased the mortality rates except in those at the limit of viability.
The goal remains to identify at-risk women as soon as possible. Careful analysis indicates that determinants of morbidity and mortality are composed of historical factors existing before pregnancy as well as factors and events associated directly with pregnancy. Historically, an attempt was made to put these together into some type of assessment technique capable of distinguishing most of the high-risk patients from the low-risk patients before delivery ( Table 2-1 ). Unfortunately, when these scoring systems have been applied to a large population base, they have not resulted in significant changes in the prematurity rates. Still, the grouping of risk factors may be of some use to the obstetrical provider because it allows for the identification of the woman who might need additional surveillance, counseling, referral, and resources.
|Socioeconomic Status||Past History||Daily Habits|
|1||Two children at home |
Low socioeconomic status
|One abortion <1 year since last birth||Works outside home|
|2||<20 years |
|Two abortions||>10 cigarettes/day|
|3||Very low socioeconomic status |
Height <150 cm
Weight <45 kg
|Three abortions||Heavy work |
Long, tiring trip
|5||Uterine anomaly |
|10||Premature delivery |
Repeated second-trimester abortion
Birth Defects and Congenital Disorders
Birth defects affect approximately 2% to 4% of liveborn infants. Contributing factors include genetic and environmental influences such as maternal age, illness, industrial agents, intrauterine environment, infection, and drug exposure. The frequency of the various etiologies of birth defects can be broken down as follows: unknown and multifactorial origin, about 65% to 75%; genetic origin, about 25%; and environmental exposures, about 10% ( Table 2-2 ).
|Birth Defect||Estimated Incidence (births)|
|Heart and circulation||1 in 115|
|Muscles and skeleton||1 in 130|
|Genital and urinary tract||1 in 135|
|Nervous system and eye||1 in 235|
|Chromosomal syndromes||1 in 600|
|Club foot||1 in 735|
|Down syndrome (trisomy 21)||1 in 900|
|Respiratory tract||1 in 900|
|Cleft lip/palate||1 in 930|
|Spina bifida||1 in 2000|
|Metabolic disorders||1 in 3500|
|Anencephaly||1 in 8000|
|Phenylketonuria (PKU)||1 in 12,000|
|Congenital syphilis||1 in 2000|
|Congenital HIV infection||1 in 2700|
|Congenital rubella syndrome||1 in 100,000|
|Rh disease||1 in 1400|
|Fetal alcohol syndrome||1 in 1000|
The terminology used to describe these anomalies is based on their underlying cause: malformation, deformation, disruption, and dysplasia. Dysmorphology is the study of individuals with abnormal features, and increased scholarship in this area has led to specialists who study birth defects and establish patterns. The result has been a better understanding of many conditions, which has improved the quality of counseling for families including possible recurrence rates in future pregnancies.
Malformations are considered major if they have medical or social implications and many times they require surgical repair. Defects are considered to be minor if they have only cosmetic relevance. They can arise from genetic or environmental factors. Deformations are defects in the position of body parts arising from some intrauterine mechanical force that interferes with the normal formation of the organ or structure. Such uterine forces could include oligohydramnios, uterine malformations or tumors, and fetal crowding from multiple gestations. Disruptions refer to defects that result from the destruction of or interference with normal development. These are typically single events that may involve infection, vascular compromise, or mechanical factors. Amniotic band syndrome is the most common example of a disruption and the timing occurs from 28 days’ postconception to 18 weeks’ gestation. Dysplasias are defects that result from the abnormal organization of cells into tissues. There are recognizable patterns in many congenital defects. The terminology to describe these patterns includes syndrome, sequence, association, and developmental field defect.
The study of congenital malformations caused by environmental or drug exposure is called teratology. An agent that causes an abnormality in the function or structure of a fetus is called a teratogen ( Table 2-3 ). About 4% to 6% of birth defects are caused by teratogens and include maternal illnesses, infectious agents, physical agents and drugs, and chemical agents. Timing of exposure to the agent plays a great role in the resulting malformation. Exposure during the first 10 to 14 days postconception can result in cell death and spontaneous miscarriage. The all-or-none theory refers to the possibility that if only a few cells are damaged, then the other cells may compensate for their loss and result in no abnormality. Most effects are seen after fertilization, but exposure prior to conception can cause genetic mutations. Mechanisms of teratogenesis are varied and include cell death, altered cell growth, proliferation, migration, and interaction. The embryo is most vulnerable during the period of organogenesis and this occurs up to the eighth week postconception, but certain organ systems including the eye, central nervous system (CNS), genitalia, and hematopoietic systems continue to develop through the fetal stage and remain susceptible.
|Type of Teratogen||Agent||Defect|
|Chemical||Retinoic Acid||Hydrocephalus, CNS migrations|
|Valproic acid||Neural tube defects|
|Phenytoin||Heart defects, nail hypoplasia, dysmorphic features|
|ACE inhibitors||Renal and skull defects|
|Misoprostol||Fetal death, vascular disruptions|
|DES (diethylstilbestrol)||Cervical cancer in daughters, genital anomalies in males and females|
|Physical||Ionizing radiation||Fetal death, growth restriction, leukemia|
|Hyperthermia||Microcephaly, mental retardation, seizures|
|Biological||Cytomegalovirus||Microcephaly, mental retardation, deafness|
|Toxoplasmosis||Hydrocephalus, mental retardation, chorioretinitis|
|Maternal||Diabetes||Congenital heart anomalies, neural tube defects, sacral anomalies|
|Phenylketonuria (PKU)||Microcephaly, mental retardation|
Maternal illness that can present a teratogenic risk involves conditions in which a metabolite or antibody travels across the placenta and affects the fetus. Maternal illness can include pregestational diabetes, phenylketonuria, androgen-producing tumors, maternal obesity, and systemic lupus erythematosus. The mother may be infected but asymptomatic. Ultrasonic findings suggestive of fetal infection include microcephaly, cerebral and/or hepatic calcifications, intrauterine growth restriction, hepatosplenomegaly, cardiac malformations, limb hypoplasia, hydrocephalus, and hydrops. Maternal fever or hyperthermia has also been associated with teratogenesis when it occurs in the first trimester and may be associated with miscarriage and/or neural tube defects ( Table 2-4 ).
|Agent||Observed Effects||Exposure Risk|
|Cytomegalovirus (CMV)||Birth defects, low birth weight, developmental disorders||Health care workers, childcare workers|
|Hepatitis B virus||Low birth weight||Health care workers, household members, sexual activity|
|Human immunodeficiency virus (HIV)||Low birth weight, childhood cancers, lifelong disease||Health care workers, sexual partners|
|Human parvovirus B19||Miscarriage, fetal heart failure||Health care workers, childcare workers|
|Rubella (German measles)||Birth defects, low birth weight||Health care workers, childcare workers|
|Toxoplasmosis||Miscarriage, birth defects, developmental disorders||Animal care workers, veterinarians|
|Varicella-zoster virus (chicken pox)||Birth defects, low birth weight||Health care workers, childcare workers|
|Herpes simplex virus||Late transmission, skin lesions, convulsions, systemic disease||Sexual activity|
Maternal ingestion of certain drugs can cause birth defects or adverse fetal outcomes. It is important that nonpregnant women are counseled about the need for contraception when using a medication that is classified as category X by the U.S. Food and Drug Administration. Maternal exposure to numerous physical and environmental agents has also been implicated as a cause of birth defects. High plasma levels of lead, mercury, and other heavy metals have been associated with central nervous system damage and negative neurobehavioral effects in infants and children. More controversial are the recent concerns over maternal exposure to so-called endocrine disruptors, bisphenol A (BPA), and phthalates, and airborne polycyclic aromatic hydrocarbons. These entities are chemicals that mimic the action of naturally occurring hormones such as estrogen. These chemicals can be found in pesticides, leaching from plastics found in water and infant bottles, medical devices, personal care products, tobacco smoke, and other materials. Exposure to them is widespread, and a large portion of the population has measurable levels. The chemicals have been associated with adverse changes in behavior, the brain, male and female reproductive systems, and mammary glands.
Our knowledge of the effects of ionizing radiation on the fetus has been based on case reports and extrapolation of data from survivors of atomic bombs and nuclear reactor accidents. Radiation exposure during pregnancy is a clinical issue when diagnostic imaging in a pregnant woman is required. Possible hazards of radiation exposure include: pregnancy loss, congenital malformation, disturbances of growth and/or development, and carcinogenic effects. The U.S. Nuclear Regulatory Commission recommends that occupational radiation exposure of pregnant women not exceed 5 mGy (500 mrad) to the fetus during the entire pregnancy. Diagnostic procedures typically expose the fetus to less than 0.05 Gy (5 rad) and there is no evidence of an increased risk of fetal anomalies or adverse neurologic outcome.
Diagnostic x-rays of the head, neck, chest, and limbs do not result in any measurable exposure to the embryo/fetus, but it is advised that the pregnant woman wear a shield for such studies. Fetal exposure from nonabdominal pelvic computed tomography (CT) scans is minimal, but again, the pregnant woman should have her abdomen shielded. Ultrasound (US) imaging has demonstrated no untoward biologic effects on the fetus or mother because the acoustic output does not generate harmful levels of heat. US has been used extensively over the last 3 decades. Magnetic resonance imaging (MRI) also has not demonstrated any negative effects.
Chromosomal abnormalities affect about 1 of 140 live births. In addition, approximately 50% of spontaneous abortions have an abnormal chromosomal pattern. More than 90% of fetuses with chromosomal abnormalities do not survive to term. In fetuses with congenital anomalies, the prevalence of chromosomal abnormalities ranges from 2% to 35%. A comprehensive, three-generation family history and ethnic origin assessment should be taken, whether evaluating preconceptionally or after birth. Congenital anomalies of a genetic origin can be sporadic or heritable and have a number of etiologies. They can involve nondisjunction, nonallelic homologous recombination, inversions, deletions and duplications, and translocations. Infants are also at a risk for having birth defects if their parents are carriers of genetic mutations. This single gene transmission pattern in humans follows three typical patterns: autosomal dominant, autosomal recessive, and x-linked conditions. These typically follow traditional mendelian genetics. Nonmendelian patterns of transmission include unstable DNA and fragile X syndrome, imprinting, mitochondrial inheritance, germline or gonadal mosaicism, and multifactorial inheritance. The most common genetic disorders for which prenatal screening may be offered are trisomy 21, trisomy 18, hemoglobinopathies (such as hemoglobin C disease, hemoglobin S-C disease, sickle cell anemia, thalassemia), cystic fibrosis, fragile X syndrome, and a variety of disorders seen most commonly in the Ashkenazi Jewish population.
Prenatal Genetic Testing for Trisomy 21
Caring for a special needs child or adult 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. Over the last 2 to 3 decades, 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 ultrasound screening provide women with choices beyond routine chorionic villus sampling 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 cut-off for risk assessment because the prevalence of trisomy 21 rises with age. Women age 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 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 has 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 advanced maternal age (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, 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 cut-off 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%.
Over the last 3 decades, 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 ultrasound is performed to search for these markers, it is called a “genetic sonogram.” The overall sensitivity of this ultrasound is 70% to 85%.
Nuchal translucency is a standard ultrasound technique and is most accurately measured in skilled hands between 10 to 14 weeks ( 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 a priori 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 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 ultrasound 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 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 a 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, 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 American College of Obstetricians and Gynecologists (ACOG) recommends that all women be offered screening before 20 weeks 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 chorionic villus sampling 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.
Trisomy 18 is also called Edwards syndrome and is the second most common autosomal trisomy, occurring in 1 in 8000 births. Many fetuses with trisomy 18 die in utero and so the prevalence of this abnormality is three to five times higher in the first and second trimesters than at birth. Prenatal screening for trisomy 18 is included with screening for Down syndrome. The analyte pattern of the first trimester test is a very low beta-hCG and a very low PAPP-A with an increased nuchal translucency. Advanced maternal age increases the risk of having a pregnancy affected with trisomy 18. These fetuses have an extensive clinical spectrum disorder and many organ systems can be affected. Fifty percent of these infants die within the first week of life and only 5% to 10% survive the first year of life. The combined and integrated tests are especially effective at detecting these affected pregnancies. The earliest detection provides for the most comprehensive counseling and earliest intervention, if desired.
Prenatal Screening for Neural Tube Defects
The incidence of neural tube defects (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 being seen 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.
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 more often seen in females versus 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 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 folic acid-deficient women preconceptually.
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 specific 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 multiples of the median (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 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 have 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 because 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.
Ultrasound can potentially detect more NTDs than MS-AFP. Detection rates depend on the type of anomaly and the trimester during which it is used. Anencephaly and encephalocele have detection rates between 80% and 90% in the first trimester, whereas detection rates of >90% for spina bifida are not seen until the second trimester. Although the vast majority of NTDs can be seen on ultrasound and the sensitivity of the ultrasound 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 ultrasound 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 ultrasound that does not explain the abnormal MS-AFP. Elevations in both amniotic fluid AFP and amniotic fluid acetylcholinesterase (AChE) suggests an open NTD with almost 96% accuracy. There is some conflict today regarding the use of amniocentesis, and some experts believe that ultrasound alone should be used given its high detection rate, absent procedure loss rate, and cost savings advantage. After reviewing the data, ACOG still recommends that the most sensitive approach to prenatal diagnosis of NTDs is the MS-AFP screening followed by ultrasound examination when elevated, and then amniocentesis if there are discrepant findings or the patient desires more information to help formulate a management decision. Magnetic resonance imaging (MRI) of the fetus can also be used when there is some factor that is interfering with ultrasound 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 recently compared 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.
Multiple gestation has been increasing in the United States. In the most recent data for 2008, the twin birth rate rose 1% to 32.6 per 1000 births. This rate has now remained essentially stable between 2004 and 2008 after rising almost 80% between 1980 and 2004. The natural occurring rate of twins and triplets in the Unites States is 1 in 80 and 1 in 8000, respectively. The likely reason for the increasing numbers of multiple births has to do with the increasing maternal age at childbirth and the use of assisted reproductive technology (ART). Maternal age, ART, parity, race, geographic origin, family history, maternal weight and height have all been associated with an increased risk of twins.
Zygosity is an important concept for multiple gestation. Twins are most commonly referred to as either di- or monozygotic. Dizygotic twins result from ovulation and fertilization of two separate oocytes. Monozygotic twins result from the ovulation and fertilization of one oocyte then followed by division of the zygote. The timing of the egg division determines placentation. Diamniotic, dichorionic (DA/DC) placentation occurs with division prior to the morula stage. Diamniotic, monochorionic (DA/MC) placentation occurs with division between days 4 and 8 postfertilization. Monoamniotic, monochorionic (MA/MC) placentation occurs with division between days 8 and 12 postfertilization. Division after day 12 results in conjoined twins. Placentation is typically dichorionic for dizygotic twins and can be mono- or dichorionic for monozygotic twins. Sixty-nine percent of naturally occurring twins are dizygotic, whereas 31% are monozygotic. Dizygotic twins are also more common with ART pregnancies and account for 95% of all twins conceived with ART.
Chorionicity is also an important concept because the presence of monochorionicity places those monzygotic twins at an increased risk for complications: twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion sequence (TRAP), and selective intrauterine growth restriction. The risk of neurologic morbidity and perinatal mortality in these twins is higher than that of dichorionic twins.
Early ultrasound assessment is a reliable way to not only diagnose multiple gestation, but to also establish amnionicity and chorionicity. It provides accurate assessment of gestational age, which can be of vital importance given the risk of preterm birth and intrauterine growth abnormalities in multiple gestation. The optimal time for this ultrasound would be in the first and early second trimester. Offering early ultrasound can also include screening for Down syndrome because each fetus is at the same risk for having a chromosomal abnormality based on maternal age and family history and all women should be offered options for risk assessment. Maternal serum analyte interpretation can be difficult in multiple gestation because all fetuses, living or not, contribute to the concentration. Measurement of the nuchal translucency can improve the detection rate by helping to identify the affected fetus. The first trimester combined test can be offered to the woman carrying multiples when chorionic villus sampling is available.
Although twins are not predisposed to any one type of congenital anomaly, monozygotic twins are two to three times more likely to have structural defects than singletons and dizygotic twins. Anencephaly, holoprosencephaly, bladder exstrophy, VATER association ( v ertebral defects, imperforate a nus, t racheo e sophageal fistula, r adial and r enal dysplasia), sacrococcygeal teratoma, and sirenomelia are the anomalies seen with increasing frequency. Most often the co-twin is structurally normal. The diagnosis of an anomalous twin is especially problematic if management might require early delivery or therapy that ultimately affects both twins. In the setting of conjoined twins, this process is even more complicated. The incidence ranges from 1 in 50,000 to 1 in 100,000 live births. Additional causes for concern in monozygotic twins are monochorionic placentas that have vascular connections. The connections occur frequently and can lead to artery-to-artery shunts and, ultimately, the TRAP sequence with reversed arterial perfusion. This results in the fetal malformation, acardiac twins. Acardia is lethal in the affected twin, but also can result in a mortality rate of 50% to 75% in the donor twin. This condition occurs in about 1% of monozygotic twins.
Growth restriction and premature birth are major causes of the higher morbidity and mortality in twins compared to singletons. The growth curve of twins deviates from that of singletons after 32 weeks’ gestation and, 15% to 30% of twin gestations may have growth abnormalities. This is more likely to be seen in monochorionic twins, but discordant growth can be seen in dichorionic twins depending on the placental surface area available to each. Twin growth should be monitored with serial ultrasound, and if there is evidence of discordance, then additional evaluation is needed. Starting in the second trimester, monochorionic pregnancies are followed every 2 to 3 weeks, whereas dichorionic pregnancies are followed every 4 to 6 weeks. There is no consensus on the optimal definition of discordance because a difference of 15% to 40% has been found to be predictive of a poor outcome. Presently, an estimated fetal weight below the tenth percentile using singleton growth curves or a 20% discordance in estimated fetal weight between the twins is the working definition of abnormal growth. Doppler velocimetry of the umbilical artery can be added to the ultrasound evaluation and may improve the detection rate of growth restriction.
The risk of preterm birth is higher for multiple gestations than for singletons and represents the most serious risk to these pregnancies. When compared to singletons, the risk of preterm birth for twins and triplets was five and nine times higher. As the number of fetuses increases, the gestational age at the time of birth decreases. In 2008, the average gestational ages were 35.3, 32, 30.7, and 28.5 weeks for twins, triplets, quadruplets, quintuplets, and higher order multiples, respectively. The rate of preterm birth for twins in the United States in 2008 was 59% before 37 weeks and 12% before 32 weeks. Additionally, 57% of these twins were of low birth weight (<2500 g) and 10% were of very low birth weight (<1500 g). Interestingly, the outcomes after delivery are similar between twins and singletons born prematurely. Preterm premature rupture of membranes is also a cause of preterm birth in multiple gestations and most often occurs in the presenting sac, but can occur in the nonpresenting twin. It seems that multiple gestations have a shorter period of latency before delivery when compared to singleton gestations.
The incidence of natural spontaneous triplet births is about 1 in 8000. Triplet pregnancy has a higher risk of maternal, fetal, and neonatal morbidity than does twin pregnancy. As the number of fetuses increases to that of the higher order multiples, these risks increase even more significantly. Some consequences found more often in these pregnancies include growth restriction, fetal death, preterm labor, premature preterm rupture of membranes, preterm birth, neonatal neurologic impairment, pregnancy-related hypertension, eclampsia, abruption, placenta previa, and cesarean delivery.
Diagnosis of a triplet or higher order multiple gestation is done by ultrasound and most instances are found in the first trimester because the vast majority of these pregnancies are conceived via ART. As with twin pregnancy, chorionicity identification is important. Monozygotic gestations can occur even though most of these pregnancies originate from three or more separate oocytes, especially in those that are spontaneously conceived. Spontaneous loss is common and it occurs in 53% of triplet pregnancies. Given the inherent increased maternal and fetal risks involved with these pregnancies, historically, fetal reduction has been offered in hopes that fewer fetuses would translate into a reduced risk. For triplet gestation, this presumption may be changing.
The risk of premature delivery or fetal death in utero of one fetus is specific to multiple gestation. The surviving fetus(es) is affected by the chorionicity and the number of fetuses. There is an ethical dilemma not seen in singleton pregnancies because one must weigh the benefits for the affected fetus against the risks of the potential interventions to the remaining fetus(es). Typically, delivery before 26 weeks is not considered because the risk of mortality is significant for all fetuses. After 32 weeks, it is appropriate to move to deliver all if one is at risk because the morbidity is considered low. Between 26 and 32 weeks is a more difficult period and remains a time when parental preference is taken into great consideration after counseling has occurred. Chorionicity helps to guide delivery when fetal death occurs because optimal management is unclear. As with twins, the risk is associated with monochorionicity and mortality is worse when this fetal demise occurs later in pregnancy.
A majority of triplets are born prematurely and 95% of them weigh less than 2500 g (low birth weight) and 35% are less than 1500 g (very low birth weight). The primary cause of these preterm births is premature labor. Multiple protocols have been tried to reduce the risk of preterm birth including decreased activity, bed rest hospitalization, home uterine activity monitoring, and tocolysis. Unfortunately, elective cerclage, progesterone supplementation, and sonographic cervical assessment also do not seem to have reduced the spontaneous preterm birth rate.
Although great strides have been made in the management of the neonate, the goal remains to reduce the risk and numbers of preterm birth or at least uncover a reliable method to predict women at the highest risk of developing preterm labor or premature rupture of membranes. This will be discussed in more detail in a separate section.
Antepartum Assessment of the Fetal Condition
Improved physiologic understanding and multiple technologic advancements provide the obstetrician with tools for objective evaluation of the fetus. In particular, specific information can be sought and obtained relative to maternal health and risk, fetal anatomy, growth, well-being, and functional maturity, and these data are used to provide a rational approach to clinical management of the high-risk infant before birth. It is important to emphasize that no procedure or laboratory result can supplant the data obtained from a careful history and physical examination and these have to be interpreted in light of the true or presumed gestational age of the fetus. The initial prenatal examination and subsequent physical examinations are approached with these facts in mind to ascertain whether the uterine size and growth are consistent with the supposed length of gestation. In the era prior to routine ultrasound dating, the milestones of quickening (16 to 18 weeks) and fetal heart tone auscultation by Doppler ultrasound (12 to 14 weeks) were important and needed to be systematically recorded. Although most of this information is gathered early in pregnancy, the significance may not be appreciated until later in gestation when decisions regarding the appropriateness of fetal size and the timing of delivery are contemplated.
A clear role for antenatal ultrasound has been established in dating pregnancies, diagnosing multiple gestations, monitoring intrauterine growth, and detecting congenital malformations. It is also integral to locating the placental site and documenting any pelvic organ abnormalities. Ultrasound is valuable when performing chorionic villus sampling or amniocentesis. Ultrasound may be used during labor to detect problems related to vaginal bleeding, size or date discrepancies, suspected abnormal presentation, amniotic fluid levels, loss of fetal heart tones, delivery of a twin, attempted version of a breech presentation, and diagnosis of fetal anomalies.
Ultrasound is a technique by which short pulses (2 µsec) of high-frequency (approximately 2.5 MHz), low-intensity sound waves are transmitted from a piezoelectric crystal (transducer) through the maternal abdomen to the uterus and the fetus. The echo signals reflected back from tissue interfaces provide a two-dimensional picture of the uterine wall, placenta, amniotic fluid, and fetus. Some indications for ultrasound are contained in Box 2-1 . In certain instances, ultrasound is performed to comply with the mother’s request only.
Confirmation of pregnancy
Fetal number, chorionicity, presentation
Placental location, placentation
Fetal anatomy (previous malformations)
Fetal well-being (biophysical profile, Doppler measurements of umbilical vessels, middle cerebral artery)
Volume of amniotic fluid (suspected oligohydramnios or polyhydramnios)
Fetal anatomy (abnormal alpha-fetoprotein)
Assist with procedures
CVS, amniocentesis, PUBS, intrauterine transfusion, external version
CVS, chorionic villus sampling; PUBS, percutaneous umbilical blood sampling.
As noted earlier, gestational age is most accurately determined the earlier it is performed during pregnancy. In the first trimester, the gestational age of the fetus is assessed by a crown-to-rump measurement and this is the most accurate means for ultrasound dating. After the thirteenth week of gestation, measurement of the fetal biparietal diameter (BPD) or cephalometry is the most commonly used technique. Before 20 weeks’ gestation, this measurement provides a good estimation of gestational age within a range of plus or minus 10 days. After 20 weeks’ gestation, the predictability of the measurement is less reliable, so an initial examination should be obtained before this time whenever possible. Such early examination also assists in interpretation of prenatal genetic screening as well as in detection of major malformations. Follow-up examinations can then be done to ascertain whether fetal growth in utero is proceeding at a normal rate.
In countries with great access to prenatal care, the problem of attending a delivery with uncertain gestational age occurs much less frequently.
When fetal growth is restricted, however, brain sparing may result in an abnormal ratio of growth between the head and the rest of the body. Because the BPD may then be within normal limits, other measurements are needed to detect the true restriction of growth. The measurement of the ratio between the circumferences of head and abdomen is particularly valuable under these circumstances.
Femur length (FL), which may be less affected by alterations in growth than the head or abdomen, is used to aid in determining gestational age and to identify the fetus with abnormal growth. Serial assessment of growth and deviations from normal, including both macrosomia and growth restriction, helps to identify the fetus at risk during the perinatal period. Calculation of estimated fetal weight (EFW) based on various fetal biometric parameters (BPD, head circumference [HC], abdominal circumference [AC], and FL) plotted against gestational age using various sonographic nomograms is an extremely useful method for serial assessment of fetal growth. Sophisticated computer software to serially plot EFW and provide percentile ranking of a given fetus is commonly used.
Three-dimensional and four-dimensional ultrasonography have added technological advancement to the imaging possibilities. Using these modalities, the volume of the targeted anatomic area can be acquired and displayed. When the vectors have been formatted, the anatomy can be demonstrated topographically. This has been a promising technique for delineating malformations of the fetal face, neural tube, and skeletal systems, but proof of clinical advantage over two-dimensional sonography is still lacking.
Early identification of any risk for neurologic injury or fetal death is the primary goal of any fetal assessment technique. The process of antenatal assessment was introduced to help pursue this underlying risk of fetal jeopardy and thereby prevent adverse outcomes. It is based on the rationale that fetal hypoxia and acidosis create the final common pathway to fetal injury and death and that prior to their development, there is a sequence of events that can be identified.
There is a general pattern of fetal response to an intrauterine challenge or chronic stress. The most widely used tests to evaluate the function and reserve of the fetoplacental unit and the well-being of the fetus before labor are maternal monitoring of fetal activity, contraction stress test (CST) and nonstress test (NST) monitoring of the fetal heart rate (FHR), fetal biophysical profile (BPP), and Doppler velocimetry.
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 ultrasound. 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 4 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 ultrasound or electronic FHR monitoring.
Just as pediatricians are taught to “listen to the parents,” prudent obstetricians pay attention when a pregnant woman thinks something is different about the pregnancy.
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 fetal heart rate 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 ultrasound 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 heart beat 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 to identify fetal well-being.
|Reactive NST||Two fetal heart rate (FHR) accelerations of at least 15 beats per minute (bpm), lasting a total of 15 sec, in 10-min period|
|Nonreactive NST||No 10-min window containing two acceptable (as defined by reactive NST) accelerations for maximum of 40 min|
|Reactive AST||Two FHR accelerations of at least 15 bpm, lasting a total of 15 sec, within 5 min after application of acoustic stimulus or one acceleration of at least 15 bpm above baseline lasting 120 sec|
|Nonreactive AST||After three applications of acoustic stimulation at 5-min intervals, no acceptable accelerations (as defined by reactive AST) for 5 min after third stimulus|
Antepartum testing is performed to observe pregnancies with an increased risk of fetal death or neurologic consequences ( Box 2-2 ). The nonstress test (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.
Maternal antiphospholipid syndrome
Poorly controlled hyperthyroidism
Cyanotic heart diseases
Systemic lupus erythematosus
Chronic renal disease
Type 1 diabetes mellitus
Decreased fetal movement
Intrauterine growth restriction
Previous unexplained fetal demise
The oxytocin challenge test or contraction stress test (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 fetal heart rate 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, 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 ultrasound 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 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 amniotic fluid volume 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, hypertension, certain fetal congenital abnormalities, maternal infection conditions, diabetes, intrauterine growth restriction, and postterm pregnancies.
Fetal Biophysical Profile
Five components—the NST, fetal movements of flexion and extension, fetal breathing movements, fetal tone, and amniotic fluid volume—constitute the fetal biophysical profile ( 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 biophysical profile 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 amniotic fluid index is normal). The false-negative rate is 0.4 to 0.6 per 1000. A normal fetal biophysical profile appears to indicate intact central nervous system (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 biophysical profile 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.
|Biophysical Variable||Normal (score = 2)||Abnormal (score = 0)|
|Fetal breathing movements||At least one episode of at least 30 sec in 30-min observation||Absent or no episode of ≥30 sec in 30 min|
|Gross body movement||At least three discrete body/limb movements in 30 min (episodes of active continuous movement considered as single movement)||Two or fewer episodes of body/limb movements in 30 min|
|Fetal tone||At least one episode of active extension with return to flexion of fetal limb(s) or trunk; opening and closing of hand considered normal tone||Either slow extension with return to partial flexion or movement of limb in full extension or absent fetal movement|
|Reactive fetal heart rate||At least two episodes of acceleration of ≥15 beats per minute (bpm) and at least 15 sec associated with fetal movement in 30 min||Less than two accelerations or accelerations <15 bpm in 30 min|
|Qualitative amniotic fluid volume||At least one pocket of amniotic fluid that measures at least 1 cm in two perpendicular planes||Either no amniotic fluid pockets or a pocket <1 cm in two perpendicular planes|
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 biophysical profile. 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 intrauterine growth restriction, 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 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 chorionic villus sampling 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 chorionic villus sampling and amniocentesis, but the immunologic platelet disorders such as idiopathic thrombocytopenia purpura (ITP) 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
Chorionic villus sampling (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 chorionic villus sampling is an increased risk for fetal aneuploidies owing to advanced maternal age, 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, neural tube defects, twin-to-twin transfusion, and polyhydramnios. It is usually performed under ultrasound 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 0.7% and 1.3% within 14 and 30 days, respectively, after a transabdominal procedure. It has been found that the loss rate may be higher with a transcervical approach. The pregnancy loss rate associated with amniocentesis has been reported to be 1 in 300 to 1 in 500. 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. 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 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 unless the following criteria can be satisfied: ultrasound measurement at less than 20 weeks of gestation that supports gestational age of 39 weeks or greater; fetal heart tones (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 either tests for the components of the fetal pulmonary surfactant (biochemical tests) or the surface-active effects of these phospholipids (biophysical tests). The lecithin to sphingomyelin ratio, 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 respiratory distress syndrome is least when the ratio of lecithin to sphingomyelin (L:S) 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 and 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.
Intrapartum Fetal Surveillance
The ultimate goal of fetal heart rate (FHR) monitoring is to identify the fetus that may suffer neurologic injury or death, and to intervene prior to the development of these events. The rationale behind this goal is that FHR patterns reflect states of hypoxemia and subsequent acidosis. It is the relationship between the condition of the mother, fetus, placenta, and labor course that can result in a poor neonatal outcome. Although one can identify risk factors such as maternal hypertension and diabetes, fetal growth restriction, and preterm birth, these conditions account for only a small number of the neonates with asphyxia at birth.
The two most common approaches are intermittent auscultation and continuous electronic FHR monitoring. There are no studies comparing the efficacy of electronic fetal monitoring (EFM) to no fetal monitoring to decrease complications such as neonatal seizures, cerebral palsy, or intrapartum fetal death. A recent metaanalysis compared intermittent auscultation to continuous EFM found as follows: the use of EFM increased the risk of both operative vaginal delivery and cesarean delivery, did not reduce cerebral palsy or perinatal mortality, and did not change Apgar scores or neonatal unit admission rates, although it did reduce the risk of neonatal seizures. The reason for this is unknown, although it is suspected that 70% of cases of cerebral palsy occur before the onset of labor. Also, the use of EFM instead of intermittent auscultation has not resulted in a decrease of the overall risk of perinatal death. Given these findings, the American College of Obstetricians and Gynecologists stated that high-risk pregnancies should be monitored continuously during labor and that either EFM or intermittent auscultation is acceptable in uncomplicated patients.
At present, continuous EFM is the preferred method of identifying the FHR pattern. This is typically performed externally through a Doppler ultrasound device belted to the maternal abdomen. The device plots the continuous FHR while another pressure transducer attached to the maternal abdomen simultaneously plots the frequency and duration of uterine contractions. These patterns can also be obtained from internal measurement of the FHR and uterine tone by a fetal scalp electrode and intrauterine pressure catheter. The scalp electrode yields a fetal electrocardiogram (ECG) and calculates the FHR based on the interval between the R waves. External monitoring is usually as reliable as internal and is the preferred method as long as it remains interpretable. A fetal scalp pH can be measured when the FHR record is difficult to interpret or in the presence of decelerations. Complications of fetal scalp blood sampling and fetal scalp electrode monitoring may include significant fetal blood loss and infections in the newborn, although these occur rarely. Fetal scalp pH sampling has largely been abandoned due to its problematic collection and poor sensitivity and positive predictive value. An alternative to fetal scalp pH determination is digital stimulation of the fetal scalp in the absence of uterine contractions and when the FHR is at the baseline. A positive test (i.e., an acceleration [15 bpm for 15 seconds] response to such stimulation) is considered fairly reliable evidence of the absence of fetal acidosis and a pH of 7.2 or greater, and clinical investigation supports its use.
Principles Related to FHR Monitoring
Despite the frequency of its use, the EFM has poor inter- and intraobserver reproducibility and a high false-positive rate. Almost 99% of nonreassuring FHR abnormalities are not associated with the development of cerebral palsy. For this reason, in 2008, the National Institutes of Child Health and Human Development convened a workshop with experts from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine to try to reach a consensus on the definitions of FHR patterns. This is a standard that has been adopted and endorsed by ACOG ( Table 2-7 ). Two major assumptions that have been made is that these definitions are primarily for visual interpretation of FHR patterns, and that they should be applied to intrapartum patterns, but are applicable to antepartum testing as well.