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Pregnancy Risks
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INTRODUCTION
The fetal environment includes all of the maternal environment and the unique
environment of the womb. Preconception and postconception risks exist for both mother
and child, and the mother's medical conditions affect her fetus. Recently, certain fetal
and maternal conditions have been shown to have environmental and genetic
components. Multivariable global effects are caused by psychosocial risks, such as
polysubstance abuse and smoking.
This course covers the following 7 topics:
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Radiation exposure
Chemical exposure
Prescription drugs
Nutrition
Drugs of abuse
Other psychosocial conditions
Medical conditions with environmental components
This article provides a summary of many psychosocial and environmental risks during
pregnancy. The complex interplay of (1) genetic, (2) environmental, and (3) social
factors requires sophisticated and thoughtful intervention efforts on the part of health
care providers. The complete health care professional must be able to deal with issues
in all 3 spheres.
RADIATION EXPOSURE
The most feared mutagen and teratogen in current times is radiation exposure. In a
broad sense, any energy-carrying waveform must be considered a kind of radiation. The
5 types of radiation considered, based on current research on exposure risks during
pregnancy, are (1) ionizing rays (x-rays), (2) cosmic rays, (3) microwaves, (4)
ultrasound, and (5) electromagnetic fields.
Ionizing rays
X-rays are the most frequent iatrogenic exposure besides prescription medications.
During their careers, all obstetricians and gynecologists are asked about the effects of
radiation exposure on a pregnancy, and they are expected to be able to judge the need
for diagnostic or therapeutic radiation. The effects of radiation are well studied, but as
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cohort age and long-term effects become clear, information continues to evolve in this
ever-changing field. Knowledge about exposures also changes rapidly.
The primary exposures are diagnostic x-rays, radiopharmaceuticals, workplace
exposures, and environmental exposures such as those that occurred after the Three
Mile Island and Chernobyl nuclear reactor accidents. Documented effects include
intrauterine lethality, organ malformation, mental impairment, and later-onset leukemia
and solid tumors.
X-rays are measured in several types of units, the most important of which are the
radiation absorbed dose (rad), which is a US measure, and the gray (Gy), which is an
international measure. Both rads and grays typically refer to single-time exposures (eg,
diagnostic procedures). The roentgen equivalent man (rem) unit of measure and sievert
(Sv) unit are used to quantify radiation exposure over time (eg, environmental releases).
Conversion factors for these measurements are 1 Gy equals 100 rad and 1 Sv equals
100 rem.
X-rays have both deterministic effects and stochastic effects. Deterministic effects are
usually intrauterine, often postconceptual, effects involving damage to growing and
pattern-forming cell populations. If the exposure occurs when cell numbers are few,
such as during the blastocyst or preimplantation stage, very early abortion or
implantation failure occurs. These effects demonstrate both a dose-response curve and
a threshold below which no effects are observed. As with other teratogens, the
embryonic stage is crucial because windows exist for the appearance of effects. The
fetal dose is also critical, and a simple application of a maternal calculated dose should
not be substituted.
The damage threshold begins at 0.1-0.15 Gy, which causes abortion at preimplantation,
and extends to 1 Gy, which is associated with fetal death in utero at term.
Organogenesis represents a window of sensitivity for the fetus during gestational weeks
3-7. The threshold is thought to be 0.05-0.5 Gy. Skeletal defects have been noted in
humans, most particularly reduced head circumference. Animal data point to more
frequent defects of the genitourinary system and eye in addition to skeletal effects.
Severe mental retardation is another human effect noted at this threshold (0.05-0.5 Gy).
The window for these effects is gestational weeks 8-25. Mental retardation has been
noted at maternal doses of 1.5 Gy. Fetuses exposed during weeks 8-25 also
demonstrate an onset of effects secondary to radiation. These effects include mental
retardation, a downward shift in intelligence quotient (IQ) of 30 IQ units/Gy, lower school
performance, and unprovoked seizure. All effects are more severe if the exposure
occurs during gestational weeks 8-15. Importantly, note that while infants of normal
intelligence remain within 1 standard deviation of normal following exposure, borderline
infants are rendered mentally retarded at relatively low exposures.
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Stochastic effects do not show a threshold, and they occur in the later years of the
exposed individual?s life. Fetal x-ray exposures are associated with later-onset
childhood leukemias and solid tumors. The demonstrated relative risk in multiple casecontrol studies is 1.39 (95% confidence interval: 1.3-1.49). This increased risk was
documented by the very large Oxford Survey of Childhood Cancers, and the finding was
confirmed by multiple US and European studies. The increased risk is thought to occur
following an exposure of 0.05 Gy.
Thyroid cancer in childhood is a special concern. Multiple studies have shown that
direct external exposure of children?s thyroids results in an increased frequency of
cancer. Such exposures occurred following the Chernobyl accident and during medical
procedures. The lag time until detection of cancer is 5 years after exposure. In contrast,
in utero exposure during the second and third trimester of pregnancy (eg, Chernobyl,
maternal thyroid ablation) is associated with an onset of childhood thyroid cancer before
the 5-year lag time; these cancers are associated with increased morbidity and
aggressiveness.
Intervention
Clearly, preventing exposure during the first trimester is advisable. Clear counseling is
needed for patients with conditions that require uptake scans or radionuclide therapy.
Patients should be advised that no known safe dose exists in regard to later-onset
childhood cancers. The balancing of risk to both patients (fetus and mother) must take
into account the value that any given diagnostic test will have for decision-making. For
occupational exposures, the limit is 1 mSv after pregnancy notification.
Medical procedures and associated fetus and uterus radiation exposure are as follows:
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Abdominal x-ray film - Fetus exposure of 0.0026-0.018 Gy
Abdominal CT scan - Fetus exposure of 0.008-0.049 Gy
Barium enema - Fetus exposure of 0.016-0.08 Gy
Chest x-ray film - Fetus exposure of less than 0.0001 Gy
Pelvic x-ray film - Fetus exposure of 0.0017-0.008 Gy
Pelvic CT scan - Fetus exposure of 0.025-0.079 Gy
Multishot intravenous pyelogram - Fetus exposure of 0.0032-0.012 Gy
Bone scan with technetium Tc 99m - Uterus exposure of 0.0033 Gy
Kidney scan with RBCs labeled with technetium Tc 99m - Uterus exposure of
0.0015 Gy
Dynamic cardiac scan with RBCs labeled with technetium Tc 99m - Uterus
exposure of 0.0034 Gy
Brain scan with technetium Tc 99 m pertechnetate - Uterus exposure of 0.0043
Gy
Thyroid scan with sodium iodide I 131 - Uterus exposure of 0.022 Gy
Cosmic rays
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Relatively few studies have been performed on human exposure to cosmic radiation.
Risks are real, but the medical community and the general public have little awareness
of them. Cosmic radiation is ionizing radiation by heavy particles, such as protons and
helium nuclei, that originate outside the earth. This form of ionizing radiation is most
evident at very high altitudes. Primary exposure requires many in-air hours; therefore,
airplane crewmembers and pilots, rather than passengers, are typically at risk.
Two organizations, the US National Council on Radiation Protection and Measurement
(NCRP) and the International Commission on Radiologic Protection (ICRP), provide the
following recommendations on permissible doses:
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General public - 1 mSv
Aircrews - 20 mSv/y averaged over 5 years (maximum 50 mSv/y)
Fetuses - 2 mSv (not to exceed 0.5 mSv/mo)
Notably, aviators generally have a lower overall incidence of cancer compared to the
general population. The risks of all other forms of transportation outweigh those of flight,
although an association exists between frequent flying and certain specific cancers,
most notably brain, colon, and hematopoietic cancers. Also, ionizing radiation has the
previously noted fetal effects of decreased head circumference, mental retardation, and
childhood cancer.
Aviation workers can easily exceed the NCRP and ICRP limit recommendations. For
example, working the London-to-Chicago route for 100 hours exceeds the fetal
recommendation. Charter jet crews and passengers fly at higher altitudes with more
consequent exposure. Changes in intensity occur with changes in solar flare activity on
the sun, and the intensity may exceed 10 mSv/h at 42,000 ft. The US Federal Aviation
Administration and the US Occupational Safety and Health Administration recognize
flight crews as individuals exposed to radiation. Computer systems are available to
calculate exposures, but these systems are not mandatory.
Intervention
Health care providers should obtain complete occupational histories and discuss risk of
exposure with pregnant patients. Given the variability of exposure and that no easy
monitoring is possible, any mandatory cut-off or exclusion of pregnant workers from
their jobs would be potentially discriminatory and may lead to risks to the child due to
altered socioeconomic status.
Microwaves
Microwaves are a form of electromagnetic radiation with particularly long wavelengths.
In contrast to ionizing radiation, which travels in extremely short, high-energy waves,
energy in microwave radiation affects objects and cells by thermal action only.
Microwaves raise the temperature within cells and are cytotoxic to individual cells only
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at high exposures. No specific DNA-damaging mechanism exists, and no stochastic
effects are observed in exposed populations.
Ultrasound
Ultrasound involves the creation of very high-frequency sound, emission of this sound,
and analysis of how the sound alters upon encountering objects of different densities
when reflected back to the emitter. Physical effects, such as well-contained thermal
effects, occur when the vibration at these very high speeds is used (eg, between the
paddles of a harmonic scalpel). The energy of ultrasound is carried by the physical
particles of the media and objects affected. The energy does not reach an ionizing level,
and no DNA-specific effects are observed.
Electromagnetic fields
Despite multiple studies, including some very large studies, the low-energy
electromagnetic fields generated by power lines, video displays, and other electric and
electronic devices have no demonstrable effects. Some of these studies have been
conducted in response to clusters of events, such as increased spontaneous abortion
rates in a specific area. MICAL EXPOSURE
Second only to the fearsome and harmful effects of radiation are the effects of
chemicals. To the general public, the presumed threat is in an obvious location, ie,
industry and environmental pollution. In reality, environmental toxins pervade the
ecosystem, and people wittingly and unwittingly expose themselves to myriad
compounds. Unlike the traceable residue of radiation from relatively few sources,
chemicals are insidious.
Two determinations must be made when a physician responds to a patient's concerns
about a specific chemical exposure. First, whether any quantity of the toxicant has an
adverse effect on reproduction in humans and, second, whether the substance is
present in sufficient quantity to affect the patient or population exposed. This issue is
complicated in human studies by the evidently high natural spontaneous abortion rate,
which makes determining the reproductive effects in humans difficult without studying
very large groups. Because as many as 15-30% of recognized pregnancies end in
miscarriage, the study population would need to be large to detect an effect. Thus,
reviewing the following criteria is useful for establishing an effect:
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The chemical exposure must precede the outcome (eg, eliminate temporal
ambiguity).
A dose-response effect is observed, which is indicated by a more severe effect
with increasing dose. Thresholds may occur.
Plausible physiological and biological mechanisms are present. For example,
positing that a major change in organ formation was due to late-trimester
pesticide exposure would not be plausible because organogenesis would be
complete.
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Findings should be replicated in other studies.
Cause can be more strongly suggested if the effect is an independent variable
after all possible confounders are eliminated.
Some researchers have recently suggested that any hypothesized chemical
toxicant should be compatible with current existing models of development and
should include cumulative risk.
Reproductive risk includes fetal effects, especially congenital anomalies. The rate of
congenital anomalies is 3% for defects that are detectable at birth in live-born infants
and 6% for defects detected by the end of the first year of life. Because these
percentages are small, if a chemical exposure conveys a modestly increased risk, a
large population of infants would need to be monitored to detect an increase in
anomalies. In addition, the gestational window is critical because exposures outside
certain gestational periods are nontoxic in the same doses that cause devastating
results within the window.
Chemicals thought to have adverse effects on reproduction and pregnancy include
endocrine disruptors, heavy metals, organic solvents, and pesticides. Although some
researchers consider tobacco smoke an environmental agent, this article includes it with
other substances of abuse. Approximately 17% of working mothers are exposed to
known teratogens in the workplace. At least 51 synthetic compounds are ubiquitous in
the environment and are also known teratogens.
Endocrine disruptors
Endocrine disruptors are chemicals that can mimic hormones, occupy hormonal
receptors, or trigger inappropriate hormone responses in the body. Naturally estrogenic
and androgenic molecules are abundant in soy and other plants. Many classes of
synthetic chemicals have estrogenic effects.
Dichlorodiphenyltrichloroethane (DDT), an organochloride, is perhaps the best-known
estrogenic pesticide. DDT is a proven reproductive toxin in birds and other wildlife. It
remains an important chemical in the environment because it accumulates within the
food chain, and unhealthy levels persist even today. DDT exposure usually occurs
through consumption of game or food with high levels of DDT, and exposure during
pregnancy is linked to low birth weight and small head circumference.
Methoxychlor, an organochloride, is an estrogenic pesticide that has largely replaced
DDT. It is thought to be safer for humans. Methoxychlor reduces rat fertility and
interferes with estrus. It also accelerates progression of pregnancy in mice, which
results in early vaginal opening. Whether any significant estrogenic effects occur in
women remains unclear.
Diethylstilbestrol (DES) is a synthetic estrogen infamous for causing uterine anomalies,
infertility, and adenosis in female fetuses exposed in utero. In utero exposure also
causes clear cell adenocarcinoma of the vagina with a young age of onset. DESFlorida Heart CPR*
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exposed fetuses typically develop vaginal cancer after 20-30 years. DES was used in
pregnant women until 1971.
Lindane is a drug used to kill lice. It has antiestrogenic and weak estrogenic effects, but
it does not occupy estrogen receptors. Heptachlor and hexachlorobenzene are also
possible endocrine disruptors.
Phthalates are chemicals used in industry, plastic production, and metal can linings. No
clear evidence links them to any human effects.
Plant estrogens from soy and legumes can adversely affect reproduction in rats and
sheep. Premature thelarche and alterations in menstruation in humans are speculated
to be associated with plant estrogens.
Intervention
Apart from the avoidance of accumulated DDT and the use of endocrine modulators
early in pregnancy, few recommendations can be made about this class of toxicant.
Metals
Heavy metals are well-established toxicants, and some can be direct industrial
contaminants into agricultural items such as fish or grain (eg, methylmercury
contamination in fish). Other metals, such as lead, are more pervasive. Lead was widely
used in paint and leaded gasoline, which has been banned; however, lead
contamination continued in soil long after use of its primary source, leaded gasoline,
was stopped.
Lead
Lead is very common in the environment and continues to be a risk today. At high
levels, it is associated with stillbirth and abortion; in the past, lead was used as an
abortive agent. Even today, as many as 52% of all homes in the United States may
have unacceptable lead levels due to lead-based paint. Safety regulations have limited
high levels of lead, but effects exist for even low levels of lead in blood. It is also
possible that lead may be mobilized from a pregnant woman's bone stores. The toxic
range for lead is 25-20 mcg/mL. Levels as low as 10 mcg/mL in maternal or cord blood
are associated with transient cognitive defects in children.
Intervention
Checking maternal serum lead values is currently performed in some public-assistance
programs. Chelation with agents such as ethylenediaminetetraacetic acid can be
considered for anyone with a lead level that is 25 mcg/mL or greater. Chelation therapy
itself may pose a hazard to the pregnancy; data from experiments in rats showed an
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increased frequency of malformations. In addition, chelation could create deficiencies in
other metals such as zinc.
Mercury
The 3 types of possible mercury exposure for pregnant women are organic, inorganic,
and elemental. Organic mercury compounds, such as methylmercury, are used in
industry as fungicides and in some paints. Uses of inorganic mercury include
antiseptics, fungicides, electrical equipment, and some illicit skin-lightening creams.
Both lead and mercury compounds have been used in cosmetics since ancient Roman
times. Elemental mercury is found in thermometers, dental amalgam, gold mines, and
batteries. It is also used as a catalyst for the formation of some chlorine compounds.
Organic mercury accumulates in the food chain, especially in fish, and it causes
neurological damage in human infants exposed in utero. An elevated incidence of
cerebral palsy and microcephaly was noted in women who ate fish from Japan?s
Minamata Bay in the 1960s following industrial contamination of the bay. Maintenance
of international standards of toxic waste management and reduction in the use of
methylmercury are necessary to limit wide-scale exposure.
Mercury amalgams may represent an occupational hazard for dental workers at all
levels. Mercury vapor (inorganic mercury) is released as these amalgams are created.
Some evidence exists for an increased risk of spontaneous abortion with more than 50
amalgam-creation exposures per week, but other research has not replicated this
finding.
Intervention
Organic mercury should be avoided completely by pregnant women. Working
environments should have a mercury vapor level below 0.01 mg/m 3. No safe level of
mercury in any form has been documented. Women should consider limiting fish intake
to no more than 350 g/wk preconceptually and during pregnancy.
Cadmium
Cadmium is found in graphic arts material, paint, ceramics, welding material, solder,
fish, and cigarette smoke. Animal research indicates that high cadmium levels can lead
to cleft palate, anencephaly, lung problems, and neurological damage. Research in
humans is underway.
Manganese
Manganese is found in tea, cloves, and some grains. Some gasoline contains
manganese additives. A low level of manganese is required in the diet. High levels of
manganese during pregnancy have been associated with an increased incidence of
clubfoot and stillbirth.
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Solvents
Manufacturing requires solvents, which are frequently used in dry-cleaning chemicals,
paint, graphics, glue, and electronics and in chemical research and production. Of the
many solvents in existence, xylene has been linked to caudal regression in humans.
Perchlorethylene may be associated with infertility, and styrene may alter menstruation.
Toluene, xylene, and perchlorethylene may be associated with increased risk of
spontaneous abortion. Recent retrospective research demonstrated increased odds of
infertility for women exposed to solvents (odds ratio, 1.74).
Dioxins
Dioxins are released into the environment during paper-pulp bleaching, pesticide
production, and the management of chlorine compound waste. Like DDT and
methylmercury, dioxins accumulate in the food chain and are harbored in adipose
tissue. They can be measured in human breast milk. In rats and monkeys, 2,3,7,8tetrachlorodibenzo-p-dioxin causes reproductive changes (eg, decreased fertility) and it
may cause endometrial hyperplasia.
In monkeys, 2,3,7,8-tetrachlorodibenzo-p-dioxin is also associated with endometriosis.
Belgium has both a high incidence of severe endometriosis and one of the highest
dioxin concentrations. In one study, women with endometriosis had higher blood dioxin
levels compared to women without endometriosis. This particular dioxin has a plausible
biological mechanism of action; one model shows that it interferes with progesteronemediated matrix metalloproteinase expression and increases cytokine release in the
endometrium.
Polychlorinated biphenyls
Polychlorinated biphenyls (PCBs) were used heavily in electronics, plasticizers, and
adhesives. They have been banned in the developed world since the 1970s. PCBs are
extremely persistent in the environment; they accumulate in fish, and they persist in
dairy products, pork, and beef. PCB exposure is linked to prenatal death, infertility, fetal
growth retardation, and poor short-term memory.
Long-term follow-up of children with high prenatal exposure to PCBs showed
significantly decreased full-scale and verbal IQ scores; the average decrease was 6.2
points. Prenatally, mothers of these children consumed fish from Lake Michigan; PCB
levels were confirmed by cord blood levels. These children were 3 times as likely to
have poor IQ performance, to have poor verbal comprehension, and to be more
distractible. They were also twice as likely to be 2 years behind unexposed children in
word comprehension.
At levels high enough to cause maternal toxicity, PCBs cause low birth weight; skin,
gum, and nail discoloration; and desquamative skin changes. Acne and nail
pigmentation are likely to persist. Some evidence suggests that some PCB actions may
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involve the thyroid hormone system. Recent innovative mechanistic studies in rat
models have shown that PCBs can act directly on uterine muscle, which increases
uterine sensitivity to oxytocin-induced contraction.
Pesticides
Many classes of compounds are used as pesticides. Examples include endocrine
modulators, such as DDT and related compounds, and organic synthetic compounds,
which are discussed in this section.
Organophosphates, such as parathion, malathion, and diazinon, have not been well
studied. Animal studies show alterations in ovarian function, decreased serum levels of
progesterone and luteinizing hormone, fetotoxicity, and pseudopregnancy.
Carbamates, such as carbaryl (Sevin), are widely used insecticides that inhibit
cholinesterases. In animal studies, even maternally toxic doses showed few increases
in defects in offspring. At the very highest doses, noted effects included omphalocele in
rabbits, ventricular septal defects in sheep, and varied anomalies in beagles.
Pyrethrums are chrysanthemum-derived insecticides found in antilice treatments. They
do not appear to have significant toxicity, but they have not been well studied in
humans.
Arbuckle and Sever reviewed epidemiological studies of numerous individual pesticides
and pesticide combinations. Overall, their review involved hundreds of thousands of
individuals. Their data suggest an increased risk of fetal death associated with
pesticides in general and with maternal employment in agricultural industries.
Intervention
Health care providers should inquire about the occupation of any pregnant patient, and
patients who work in agricultural industries should be advised accordingly. Avocations
such as gardening should not be forgotten in the initial prenatal workup and counseling.
PRESCRIPTION DRUGS
Drugs are intentionally ingested chemicals that achieve measurable levels in the body
and are usually used for therapeutic effects. Drugs are far more likely to be measurable
in the fetal circulation compared to other chemicals, and they usually have documented
teratogenic effects. As with chemicals, a vast panoply of drugs are manufactured, and
their use is widespread. Recent studies indicate that more than 90% of pregnant women
take medication during pregnancy, and many women take more than 4 different drugs
during the course of pregnancy.
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The US Food and Drug Administration (FDA) requires animal testing before they
approve new medications. The FDA also uses a classification system to define fetal
risks for all FDA-approved drugs. The pharmaceutical pregnancy risk classification by
the FDA is as follows:
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Category A: No fetal risk is observed in human studies.
Category B: No fetal risk is observed in animal studies. No human risk is
observed, although there is some risk in animals.
Category C: No studies are available. Adverse effects are observed in animals,
but no human studies are available.
Category D: Evidence exists of increased risk to human fetus. The benefits of the
drug may outweigh its risks.
Category X: The drug has a proven risk to humans that outweighs any potential
benefit.
Importantly, keep in mind that the same parameters used when considering the
teratogenicity of chemicals also apply to drugs. An important developmental window
may exist during which an effect can occur. Organogenesis, which occurs during
postconception weeks 2-8, is the most important window. The drug must be able to
access the fetus through the placenta, or it must be able to interact with maternal
systems to create the effect.
Because of specific observable teratogenicity, several medications have been placed on
the US Toxics Release Inventory by the Environmental Protection Agency. These drugs
include lithium, nicotinic acid and salts, pentobarbital, phenytoin, and tetracycline.
Exposures to some kinds of medications are followed in national registries. These
registries follow patients for very long-term effects. Examples include DES,
anticonvulsants, and psychotropic medications.
Medications can alter the fetal environment and pose a risk to fetal development. This
risk must always be weighed against the benefit to the mother in the treatment of
serious medical and mental conditions.
A complete review of medication use during pregnancy is beyond the scope of this
article. An essential reference on the use of specific medications during pregnancy is
Drugs in Pregnancy and Lactation by Briggs, Freeman, and Yaffe; this text is available
from Williams & Wilkins. William's Obstetrics also has concise but fairly comprehensive
information on this topic; this text is available from Appleton & Lange. In addition, some
major tertiary care centers and university hospitals have hotlines analogous to poison
center hotlines for questions about medications during pregnancy.
Retinoids
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Vitamin A?related compounds are essential for normal development and pattern
formation in the early embryo. For this reason, medications based on these molecules
are among the most potent teratogens.
Vitamin A is teratogenic in quantities of more than 10,000 IU/d, and many types of
vitamins include doses of vitamin A at this level or higher. The risk of structural
anomalies is 25%, and an additional risk of mental retardation is 25%. Congenital heart
disease, eye and ear malformation, cleft palate, and cortical blindness are frequent
occurrences. Beta-carotene, which is a naturally occurring precursor to vitamin A in
vegetables, does not have any teratogenic effect.
Isotretinoin is a common dermatological drug used in acne treatment. Use during early
pregnancy is associated with a pathognomic group of anomalies. Microtia, anotia,
micrognathia, cleft palate, conotruncal heart defects, thymic abnormality, and brain
malformation have been observed. The half-life of isotretinoin is 12 hours, and
cessation of the drug before conception prevents isotretinoin embryopathy. Unique
consent forms and contracts for adequate contraception have been developed for the
use of this medication in women of childbearing age.
Etretinate is an extremely long-lasting oral retinoid used in the treatment of psoriasis.
The medication is detectable in serum for more than 2 years after use. Neural tube
defects, CNS malformations, skeletal abnormalities, and craniofacial defects have been
observed. The duration with which the drug may continue to cause abnormalities is
unknown. Etretinate should not be used in women of childbearing age.
Topical tretinoin is used as an acne treatment. It is metabolized by the skin and is not
associated with congenital anomalies.
Thalidomide
Thalidomide is the sole drug in a unique class of sedatives. Despite years of study and
use, its exact mechanism of action is unknown. When first isolated and produced,
thalidomide was a racemic mixture with an extraordinarily variable range of effects. Its
primary adverse effects involved the nervous system, and it was marketed as a safe
drug with no potential adverse outcome. Despite the fact that testing did not show an
increase in congenital anomalies in animals, thalidomide proved to be a potent and
specific teratogen in humans. Defects appear in a precise order, depending on the
exact timing of the thalidomide use. The progression and teratogenic effects associated
with the use of thalidomide are as follows:
1.
2.
3.
4.
Used 12-27 days postconception - External ear defects
Used 27-30 days postconception - Upper limb phocomelia
Used 30-33 days postconception - Lower limb phocomelia
Used 35-39 days postconception - Triphalangism of thumbs
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Thalidomide began an as over-the-counter drug in Germany and Europe. It initially
failed to receive FDA approval; thus, it was not legally available in the United States for
decades. When its adverse effects and teratogenicity were revealed, it became a
prescription medication in Europe. Recently, thalidomide was approved in the United
States in a very limited fashion with a unique informed consent partially based on
retinoid consent forms. It is an effective medicine for leprosy, graft versus host disease,
some rheumatological diseases, and some forms of cancer. Phocomelia was much
more frequent in countries in which thalidomide was continuously available. Germany,
for example, had more than 5000 cases, while the United States had only 17.
Diethylstilbestrol
DES is a synthetic estrogen that was used during early pregnancy in women with a
history of miscarriage and hyperemesis. Exposure of female fetuses before gestational
week 9 resulted in a 70% incidence of vaginal adenosis among female offspring. In
these women, reproductive tract malformation is very common and distinctive. Findings
include cervical hoods and combs, a T-shaped uterus, a shortened vagina, and cervical
stenosis. Reproductive capability is markedly reduced in these women. The United
States has approximately 250,000-1,000,000 DES daughters. An estimated 1 in 1000
DES-exposed daughters develops vaginal clear cell adenocarcinoma, a formerly rare
cancer previously observed in women aged 70 years and older. DES sons have an
increased rate of cryptorchidism, epididymal cysts, and hypoplastic testes, but they do
not have decreased fertility. DES was removed from the market in 1971.
Anticonvulsants
Epilepsy is a very common disorder that affects women of reproductive age. Frequently,
a history of seizure leads to concerns about anticonvulsants during pregnancy. The risk
for malformation doubles with use of anticonvulsants, and a few distinct syndromes are
observed. The decision to cease an anticonvulsant is complicated by the fact that
seizure itself may predispose the fetus to an anomaly. In late pregnancy, placental
hypoxia can occur during prolonged seizure. In addition, many common anticonvulsants
can contribute to folate deficiency. Heritable epilepsy also may be associated with other
genetic abnormalities.
Valproic acid is associated with increased risk of neural tube defects. Phenytoin is
known to decrease the absorption of folate. All the anticonvulsant syndromes (ie,
phenytoin, carbamazepine, and trimethadione syndromes) share common effects such
as reduced intellectual capability and craniofacial abnormalities. Growth deficiency,
epicanthal folds, and nail hypoplasia are frequent findings. Only trimethadione
syndrome is associated with simian creases in the hands, cardiac anomalies, and
irregular teeth.
Phenobarbital is not associated with an increase in any anomaly, but it was associated
with decreased intellectual performance at age 22 years in a Danish registry.
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Intervention
If the patient has been seizure-free for 2 years, she may attempt a trial withdrawal
during attempts at conception or during early pregnancy.
Anticoagulants
A recognizable warfarin syndrome is observed with warfarin (Coumadin) use.
Developmental delay, hypoplastic nasal bridge, microcephaly, growth retardation, and
eye malformation are prominent. However, catastrophic results can occur in women
with hypercoagulable states.
Intervention
If possible, the patient should be converted to heparin before conception.
Antihypertensives
Certain well-studied older drugs are preferred for use during pregnancy for women who
are chronically hypertensive and those with pregnancy-induced hypertension. Diuretics
can lead to oligohydramnios. Calcium channel blockers may lower blood pressure very
rapidly and result in fetal hypoperfusion; thus, they should not be used long-term.
Angiotensin-converting enzyme inhibitors should not be used at any point during
pregnancy.
Effects include the following:







Oligohydramnios
Renal anomalies
Neonatal renal failure
Pulmonary hypoplasia
Hypocalvaria
Intrauterine growth restriction (IUGR)
Death
Intervention
Women with chronic hypertension should undergo preconception conversion to
methyldopa. Women with pregnancy-induced hypertension should be monitored by their
obstetrician or perinatologist as necessary.
Psychotropic medications
Women with mental illness are in a similar situation to women with epilepsy. Many of
the most effective medications have fetal effects, but many conditions, such as severe
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depression, manic depression, and psychosis, can have equally severe effects on both
mother and fetus if untreated.
Antidepressants
Lithium use is suggested to increase the risk of Ebstein anomaly, which is a severe
cardiac defect. To date, further studies have not demonstrated severe teratogenicity
with lithium use. Maternal sodium balance and fluid balance must be maintained as
maternal metabolism changes throughout pregnancy. Many women who experience
manic-depressive episodes (ie, bipolar disorder) must make a difficult choice because
lithium may cease being efficacious if it is started and stopped too frequently.
Selective serotonin reuptake inhibitors are common antidepressant drugs. Fluoxetine
(Prozac) is a class B antidepressant that is preferred during pregnancy. Bupropion
(Wellbutrin) is another class B medication. Monoamine oxidase inhibitors should be
avoided due to the potential for hypertensive crisis.
Benzodiazepines
In 1992, researchers reported a potential benzodiazepine syndrome that included
dysmorphism, growth restriction, and CNS dysfunction. Because these patients are
frequently polysubstance abusers, completely separating this syndrome from other
teratogenic effects is impossible.
NUTRITION
The overall nutritional status of the mother contributes to the environment of the fetus,
but few deficits or surpluses are fetal risk factors.
Folate
Folate is essential in many metabolic pathways, especially synthesis of nucleic acids
and amino acids. Strong evidence from prospective studies demonstrates that folate
deficiency is associated with neural tube defects and spina bifida. An association is also
observed with cleft lip and cleft palate. Aminopterin, a folate antagonist, is a known
teratogen.
Intervention
The recommended daily supplement for pregnant women without risk factors is 0.4 mg
of folate. Patients who are at risk for a defect, especially women who previously have
given birth to an affected infant, should take 4 mg/d. As with many other active
molecules during pregnancy, effect timing is important. Because the neural tube closes
at 26-28 days of gestation, preconception supplementation is best. Recent policies in
many countries, including the United States, have provided supplementation in all
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grains and flours. On average, women who consume these supplemented products
should reach the recommended daily value of 0.4 mg.
Retinoids and other vitamins
Excessive intake of vitamins is most frequently encountered in patients using megadose
vitamins. Excessive intake can have effects on both the mother and fetus. Effects range
from no effect (most water-soluble vitamins) to reversible neuropathy (at least 500 mg/d
of vitamin B-6) to severe congenital defects (vitamin A precursors and derivatives).
Vitamin A is a fat-soluble retinoid that can be stored in body fat for long periods. High
levels are associated with a dose-dependent increase in fetal malformations such as
hydrocephalus, microcephalus, and cardiac defects. Beta-carotene, the natural
precursor found in orange vegetables, is not associated with congenital defects.
Retinoids are now recognized as important pattern-formation molecules during very
early embryogenesis.
Various other effects occur from vitamin overdose. Extreme levels of vitamin D intake
(>15 mg/d) are noted in patients with soft tissue calcification. Excess iodine is
associated with goiter and hyperthyroidism. Taking more than 45 mg/d of zinc has been
associated with preterm delivery. High fluoride intake (>2 mg/L) can cause dental
fluorosis of the baby?s primary teeth.
Intervention
Avoid doses of vitamin A that exceed 10,000 IU because doses higher than 25,000 IU/d
clearly exceed baseline risk.
Iron
Pregnancy carries a risk of iron deficiency anemia to the mother because of increased
hematopoiesis and stores for the baby. The mother?s need totals at least 7 mg/d of
iron. Severe iron deficiency anemia (and other anemias) confers a risk of low birth
weight, preterm birth, and increased perinatal mortality to the infant if the maternal
hemoglobin level falls below 10.4 ng/mL. Some controversy exists regarding
supplementation during pregnancy because a hemoglobin level of higher than 13.2 g/dL
is associated with progressively higher incidences of pregnancy-induced hypertension,
neonatal mortality, low birth weight, and preterm delivery. No evidence indicates that
iron supplementation is the etiology; rather, severe maternal conditions that contract the
plasma volume (eg, severe early preeclampsia) are suggested. Maternal smoking is
also associated with relatively high hemoglobin levels and could be a factor in these
findings.
Intervention
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Iron supplementation, at least after the fourth month of pregnancy, helps prevent severe
anemia. Between-meal dosing is best. Although vitamin C aids absorption,
simultaneous calcium or magnesium intake can inhibit iron absorption. Approximately
30 mg/d of elemental iron is recommended for most pregnant women. A higher risk of
anemia is associated with multiple pregnancies. Importantly, keep potentially dangerous
amounts of iron pills from young children in the household. Iron fumarate is the most
easily absorbed form.
General nutrition risks
A logical assumption is that a total energy deficit would be associated with smaller
babies or IUGR. However, the evidence does not support a simple relationship between
these two variables. Data from several well-studied groups of women who were
subjected to food rationing and famine during war show that extreme restriction of
energy (caloric) intake (range, 1883-3347 kJ/d [450-800 kcal/d]) was associated with an
average decrease in final birth weight of 250-535 g. These studies were conducted
through World War II in the Netherlands and in Leningrad (since renamed St.
Petersburg). In the Netherlands, the population of newborns was assessed at maturity.
Males of that generation were examined for mandatory military service; no long-term
sequelae were noted except for overall smaller stature. No effects on intelligence or
mental function were observed.
In the past, opinions have varied on the appropriate weight gain during pregnancy. Thin
women (<19 body mass index) who have poor weight gain during pregnancy are clearly
at risk for having an infant that is small for gestation age or has IUGR. In addition,
mothers who gain the most weight (>2 standard deviations above the norm) are at risk
for larger infants and higher cesarean delivery rates. Approximately 22% of women who
gain the most weight have cesarean deliveries, compared to 16% of those who gain the
normal amount of weight.
Intervention
Nutrition should be assessed throughout pregnancy to uncover important deficits and
discover important risks such as overuse of vitamin A or extremes in weight gain.
According to the American Board of Obstetricians and Gynecologists, women who are
considered underweight prepregnancy should gain 28-40 lb, women who are
considered normal weight prepregnancy should gain 25-35 lb, and women who are
considered overweight prepregnancy should gain 15-25 lb.
DRUGS OF ABUSE
Substance abuse is the deliberate use of licit or illicit drugs and substances for
recreation or self-medication. It has affected humankind since the inception of
civilization, and it should come as no surprise that many pregnant and reproductiveaged women use or abuse these substances.
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While women are likely to self-report radiation exposure and seek help if they have
concerns about an occupational or chemical hazard, those who use abuse drugs are
more likely to deny the seriousness of their condition. Individuals who abuse drugs are
also more likely to be reluctant to seek help due to the extreme stigma associated with
their condition. As is the case with prescribed medicines, the use of multiple substances
is more common than the use of a single substance. Depending on the study, random
urine screening produced positive results in 15% (range, 5-20%) of samples. Substance
use is prevalent across socioeconomic, racial, geographic, and cultural lines. An
estimated 500,000 infants are exposed each year. Virtually every practitioner who
encounters pregnant women also encounters pregnant women who use substances.
The most frequently abused substances, in order of documented severity of fetal
effects, are alcohol, tobacco, barbiturates, narcotics, cocaine, less common drugs,
inhalants, and caffeine. Keep in mind that most severe effects result from the use of
multiple substances, which is the most common form of substance abuse. The high
frequency of multiple-substance abuse creates difficulty in designing and completing
studies of single agents.
Alcohol
Alcohol is the most potent teratogen among the substances of abuse. Fetal alcohol
syndrome (FAS) now surpasses all other known etiologies for mental retardation. A
dose-dependent range of effects exists, and a threshold for effects is theorized, but not
proven. In animal studies, even a single dose (comparable to a single binge of at least
4.5 drinks) causes pregnancy failure, craniofacial abnormalities, and CNS dysfunction.
FAS occurs at a consumption level typically at or above 21 drinks per week, which is
approximately 3 drinks per day for heavy drinkers. The dose-response curve means that
partial syndromes occur, which has led to a new suggested categorization of FAS and
partial FAS.
The first 3 categories are considered equally severe. The partial syndromes and effects
are seen at lower levels of alcohol consumption (eg, 2 drinks per day). Drinking during
the first trimester is associated with physical defects; growth restrictions and
neurological effects are associated with second- and third-trimester alcohol
consumption. Studies have demonstrated reduced incidence of ARND if heavy drinkers
stop drinking for the second and third trimesters.
Intervention
Given the high prevalence of drinking in the United States (70%) and the worldwide
incidence of FAS (1 case per 1000 births), every effort should be made to identify
pregnant persons with drinking problems. Because benefit can be derived from ceasing
alcohol consumption later in pregnancy, tools to detect those with drinking problems
should be implemented at multiple points, not just at entry into prenatal care.
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To place the risks of alcohol consumption during pregnancy in perspective, persons
who drink heavily should be advised that 30-40% of infants born to mothers who
consume more than 2 drinks a day in the first trimester will have the full-blown FAS
syndrome. This is one of the highest known rates of malformation caused by
substances. Only the most potent retinoids approach a malformation rate of 50%, and
even the notorious thalidomide had overall rates of malformation far below those of
alcohol. Also, when folate deficiency and subsequent neural tube defects are examined,
the highest-risk population incidence approached 5%, which is much less that the rate
of FAS in mothers who are heavy drinkers.
Those identified as problem drinkers should undergo withdrawal in a sheltered setting,
and they should avoid the use of benzodiazepines and, if possible, other sedatives. The
majority of these individuals withdraw successfully or significantly reduce alcohol intake
(67% succeeded in a Boston City Hospital program).
Small doses of pentobarbital can be used in place of benzodiazepines. Disulfiram
should be avoided because it is teratogenic. After withdrawal, long-term treatment and
support are necessary. Importantly, view all dependencies and addictions as chronic,
possibly life-long illnesses. Relapse is very frequent. Counseling can be supplemented
with naltrexone (category C), an opiate antagonist, even in pregnancy. Use caution with
naltrexone because it can precipitate acute withdrawal from narcotics and should be
discontinued 72 hours before labor. A major benefit is its ability to reduce alcohol
cravings.
Persons who abuse alcohol have a high frequency of cigarette smoking, and some of
the growth restriction associated with FAS may be attributable to tobacco. The other
most frequent illicit substance used by persons with alcoholism is marijuana. Phenytoin
effects also may be additive.
Tobacco
Cigarette smoking is also very prevalent in society. Recently, Wollman coined the
phrase ?fetal tobacco syndrome? in exact parallel to FAS. The major effects of smoking
during pregnancy are growth restriction, increased miscarriage rate, perinatal mortality,
and childhood effects.
Cigarette smoking is the most important cause of IUGR in developed nations,
accounting for an astonishing 40% of cases. A well-documented dose-response curve is
observed, ie, fetal weight decreases as the number of cigarettes smoked by mother
increases. Fetal weight is reduced 5 percentile points per pack per day. The morbidity
and health dollar expense is probably equal that of pregnancy-induced hypertension.
The incidence of premature birth is also increased.
Twelve of 13 recent studies demonstrated reduced fertility (by 50%) and other adverse
reproductive outcomes in women who smoke. Risk includes pregnancy loss. Daughters
of women who smoked during pregnancy have 4-fold increased risk of taking up
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smoking in adolescence. This effect persisted after controlling for postnatal smoking,
and the effect did not seem to occur in sons of mothers who smoked.
Smoking alters the overall success rate of assisted reproductive technologies by 40%.
In addition, women who smoke have a 50% reduced implantation rate and a 50%
reduced ongoing pregnancy rate. Women who quit smoking prior to attempting assisted
reproduction fare better. Women who smoke have increased levels of follicle-stimulating
hormone (FSH), more abnormal oocytes in the ovary (diploid after meiosis), and early
menopause.
Perinatal mortality rates are increased due to the association of both prenatal and
postnatal smoking with sudden infant death syndrome (SIDS). SIDS has a prevalence
of approximately 0.63 cases per 1000 births, and it is the most common single cause of
postnatal death. The pervasive influence of smoking on birthweight is a contributing
factor. In multiple studies, SIDS was approximately twice as prominent in women who
smoked. Increases occurred when other members of the household smoked, and the
effects seemed multiplicative, ie, the more individuals in the household who smoke and
the higher the estimated exposure and number of cigarettes per day, the higher the rate
of SIDS. Separating prenatal effects from postnatal effects is very difficult, but evidence
indicates independent increases in risk for both.
The adverse effects of prenatal smoking and passive smoking continue into the child?s
life. In the immediate neonatal period, withdrawal from nicotine is seen in a "jittery baby"
constellation of symptoms. Also, asthma is linked to both prenatal and postnatal
smoking. Overall lifetime lung function capability is decreased, regardless of whether
full-blown asthma develops.
Intervention
Clearly, the potential to eliminate 40% of IUGR cases in the United States indicates that
eradicating smoking in pregnancy a worthy goal. As is the case with alcohol, warning
labels on cigarette packages have increased public awareness of the dangers of
smoking during pregnancy. Yet, despite public awareness, smoking in certain groups,
such as young women and women in inner city areas, persists and even increases.
Whether recent public efforts to terminate cigarette advertising directed at children,
stricter vending laws, and direct antismoking advertising will succeed remains to be
seen. Also, evidence exists that cigarettes are more addictive for women than men and
that women have more difficultly quitting smoking compared to men.
Because nicotine crosses the placenta and withdrawal occurs in the neonate, nicotine
patches are not an appropriate method of smoking cessation for the mother. Counseling
and support groups are recommended. Bupropion (category B) is an antidepressant
that could be considered for women during late pregnancy, especially if they have a
combination of depression and smoking.
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As with alcohol, a stigma is attached to smoking during pregnancy, and questioning
about smoking must be frank but supportive and occur at multiple points, not just at
entry to care.
Barbiturates
Sedatives are both widely abused, especially in polysubstance abuse, and widely
prescribed. While not known to be directly teratogenic, barbiturates cause tolerance and
abstinence (withdrawal) syndromes in both the mother and fetus. Both severe
intoxication and withdrawal can cause maternal death. Thus, barbiturate abuse is listed
third in severity in this article.
Along with benzodiazepines, barbiturates are used to counteract the effects of use and
withdrawal of alcohol, cocaine, and amphetamines. Those who abuse barbiturates are
generally heavily inculcated in the drug subculture and are most at risk for poor
nutrition, poor prenatal care, sexually transmitted diseases (STDs), prostitution, and
violence.
Many of the features of maternal withdrawal are observed in fetal withdrawal. Premature
labor can be precipitated by sudden withdrawal.
Intervention
Identification of the problem, a multidisciplinary team approach, and intervention at
multiple time points are essential. A 4-question CAGE (ie, cut down, annoyed, guilt,
eye-opener) survey, which is similar to the TACE survey for alcohol, can be used.




Cut down: Have you felt the need to cut down on your drug use?
Annoyed: Have you been annoyed by criticism of your drug use?
Guilt: Have you felt guilty about your drug use?
Eye-opener: Have you felt the need for an eye-opener to avoid withdrawal or
recover from use of drugs?
One point is given for an affirmative answer to each question. A score of 1 is
concerning, and a score of 2 indicates a high likelihood of abuse.
Step-down withdrawal in increments using phenobarbital or pentobarbital is the
treatment of choice. Treatment of intoxication includes supportive measures, gastric
lavage during early intoxication, medication to support blood pressure, and
hemodialysis.
Narcotics
Heroin has recently regained popularity as a drug of abuse. Currently, it is more
frequently smoked or snorted than it was in the past. A large number of persons who
use heroin still inject, and particular risks exist for pregnant women who inject. Recent
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work in North America addresses the different experience of women in the drug
subculture and identifies some of the factors that lessen the effectiveness of treatment
and outreach.
As many as 39% of females who abuse substances, specifically those who inject
substances, have a history of current or past sexual or physical abuse. One large North
American study finds that 65% of women in methadone programs have been sexually
and/or physically abused within the preceding 12 months.
Physiologically, women may be more swiftly addicted, and they have less success
withdrawing. Women have fewer resources to maintain sobriety, and treatment
programs may not provide childcare or protect women from harassment. Women may
not be able to modulate risk factors during drug use because they are often second on
the needle to their male partners or they are injected by their male partners. Women
who abuse drugs may support their habit through prostitution. This constellation of
issues results in high rates of infection with human immunodeficiency virus (HIV). Poor
outcome is compounded by the fact that women who abuse substances and are HIVpositive are half as likely as men to receive appropriate antiviral therapy.
During pregnancy, treatment is further complicated by fear and mistrust of the medical
system, including fear of incarceration and, justifiably, fear that their babies will be
removed from their care. Cessation of narcotics produces withdrawal in both the mother
and fetus. Typically, this is not as life-threatening for the mother compared to withdrawal
from alcohol or barbiturates. Early in pregnancy, withdrawal from narcotics may kill the
fetus by causing expulsion of a very premature fetus. In utero fetal withdrawal may
result in hypoxia, hyperactivity, meconium passage, and, ultimately, intrauterine fetal
demise. Causes of maternal death can include overdose in those who use less
frequently and overdose from adulteration of street drugs in those who use frequently.
Maternal narcotic use during development is not frankly teratogenic, but IUGR,
premature delivery, and chorioamnionitis occur.
Intervention
Much of the risk to the fetus can be ameliorated by the use of clonidine and naltrexone
to detoxify. In addition, methadone or levomethadyl acetate (LAAM) help maintain
abstinence. Naltrexone is a long-acting antagonist of opioid receptors. Methadone and
LAAM are opiate agonists that blunt cravings and/or block the euphoric effects of
narcotics. Patients become methadone-dependent and can withdraw. LAAM does not
have this effect, and it is a very long-lasting agent.
Treatment of overdose should include resuscitation and support and reversal of the
narcotic effects with a fast-acting antagonist such as naloxone (Narcan). Pulmonary
edema may occur. Chronic lung changes from repetitive injury by particulate matter in
diluents may worsen the prognosis and prevent resuscitation. Treatment should be
performed in organized programs, under direct supervision in a sheltered setting. A
team approach with high-risk obstetric involvement is best.
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Cocaine
Over the past 175 years, cocaine has waxed and waned in both popularity and the
concern its use invokes. Initially available over the counter and in Coca-cola syrup, it is
now the predominant target in the "war against drugs.? The increased availability of the
inexpensive freebase form, crack cocaine, has led to rampant use across all
socioeconomic groups since the late 1970s. Concern about cocaine use by pregnant
women has also waxed and waned over the past 2 decades.
Without question, cocaine use, especially crack use, has severe effects on the user.
Effects include vasoconstriction, hypertension, seizure, respiratory collapse, crack lung,
cardiac arrhythmia, and fatal myocardial infarction. The lethal dose is 1.2 g, but death
has occurred with as little as 20 mg. During pregnancy, cocaine use is associated with
hypertension, seizure, preterm labor, placental abruption, IUGR, and preterm delivery.
Pregnant women may show an exaggerated response to cocaine toxicity, perhaps due
to progesterone-induced alterations in the enzyme systems that metabolize cocaine.
Cocaine is not a teratogen. Early concerns that its use might be associated with limb
reductions and other vascular anomalies have not been substantiated. The
catastrophes that were predicted because of increased cocaine use, such as large
numbers of children with attention deficit and other permanent behavioral problems,
have not occurred. Cocaine abuse, especially crack cocaine use, is a politicized issue,
much like abortion. With the onset of crack's availability to economically disadvantaged
minorities came a punitive mindset in the majority.
Many states passed laws that treated substance abuse in women as a criminal or child
abuse offense that was sometimes considered a felony. While some cases have
involved alcohol or refusal of medical advice, the vast majority of charges have been
brought against economically disadvantaged minority women. An African American
women is 10 times more likely to be prosecuted for such a charge than a white woman,
although the overall substance abuse rates in white and minority women are the same.
This disparity is so clear-cut that some federal judges have refused to follow sentencing
guidelines set forth in some states. The ultimate result of this focus on "crack babies"
and criminalization has been reduced access to treatment for persons who abuse
substances.
Intervention
Research continues into the possible subtle effects of prenatal exposure to cocaine.
The bulk of effects observed thus far involve affective disorders and language skills. All
effects resolve within 1-2 years of birth. Cocaine abuse is an important marker for
polysubstance abuse and a chaotic home life. Importantly, remember that supportive
measures, nutritional education and support, and provision of regular medical care
ameliorate the effects of cocaine on the fetus. Treatment should be the goal.
Amphetamines
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Amphetamines are abused by all routes, ie, oral, intravenous, and inhaled. They affect
the adrenergic systems and are sympathomimetic. Symptoms of use include euphoria,
hyperactivity, paranoia, anorexia, insomnia, hallucinations, and decreased attention to
pain. Chronic use generally leads to severe malnutrition. Amphetamines can cause
severe arrhythmia, including ventricular tachycardia and asystole during obstetric
anesthesia. Amphetamines cause a withdrawal syndrome in babies that mimics the
lethargy and severe depression observed in persons who use regularly but are
abstaining.
When inhaled, adverse effects are similar to crack and include placental abruption,
IUGR, and preterm delivery. When injected, infectious sequelae are observed, including
endocarditis. An amphetamine-specific vasculitis can occur and result in renal, cerebral,
and pulmonary compromise.
Intervention
Those who abuse amphetamines frequently use other drugs, especially cocaine.
Detoxification and restoration of nutrition before delivery lead to better outcomes.
Hallucinogens
Substances such as lysergic acid diethylamide (LSD) and phencyclidine (PCP) alter
sensation and produce hallucinations. Self-induced and accidental trauma are common
and are often secondary to the labile mood induced by these substances.
Some evidence indicates that LSD can produce chromosomal anomalies. A few cases
point toward spastic muscle change and craniofacial abnormalities in infants of persons
who use PCP. Importantly, note that these drugs are frequently adulterated with a
multitude of different substances, including warfarin and other teratogenic substances.
Intervention
Users of hallucinogens frequently abuse numerous substances. The individual may be
at risk of harming herself or others, or she may be harmed during restraint. Designer
drugs may not produce a positive test result on standard toxicological screening tests.
Inhalants
Adverse events for mother and baby may be increased when substances of abuse are
inhaled, as in the case of cocaine and amphetamines. Others inhale substances such
as glue, solvents, or paint thinner in order to achieve a high. This practice is especially
frequent in children and young adolescents. Also known as huffing, aerosol propellant
from cans may be used. Maternal and fetal renal tubular acidosis, pulmonary injury, liver
damage, bone marrow toxicity, neural damage, and cardiac arrhythmia may result.
Preterm delivery, IUGR, and intrauterine fetal death have been reported.
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Intervention
Importantly, consider this form of substance abuse when confronted with an adolescent
in preterm labor. Beta-mimetics that are administered to treat preterm labor (eg,
terbutaline) exacerbate arrhythmias and are contraindicated in these patients.
Caffeine
Caffeine is widely considered a very benign substance, and it is ubiquitous in coffee,
tea, and soft drinks. The estimated average daily intake is 99 mg. A cup of coffee can
contain 127 mg of caffeine, tea up to 107 mg, and soft drinks up to 65 mg. In one study,
approximately 28% of women consumed more than 150 mg/d throughout their
pregnancy. At levels equivalent to 12-24 cups of coffee a day, rats experience skeletal
malformations and ectrodactyly; however, teratogenic effects have not been noted in
humans. Recent studies do indicate a slightly increased chance of experiencing preterm
delivery, having an infant that is small for gestational age, and, perhaps, miscarrying in
the late first or second trimester.
Intervention
Pregnant women should keep caffeine intake below 150 mg/d, especially early in
pregnancy.
Just as substance abuse issues exist in all realms of society, so too do psychosocial
issues, including violence, depression, anxiety, and inequities of care. These
psychosocial issues can greatly affect pregnant women and their children.
Violence
Estimates indicate that 1 in 4 women experiences physical abuse within her lifetime.
Physical abuse during pregnancy occurs at an incidence of 5-17%. Data concerning
variation in different ethnic and socioeconomic groups are conflicting. Some studies
indicate a higher rate of violence against white and Hispanic women compared to
African American women.
Recent studies show that pregnancy is not a time of protection from violence, and it can
be a time of escalation of violence, especially during the postpartum period. Martin and
colleagues found that 77% of abused women sustained physical injury when abused
during the postpartum period. Other studies have shown that abuse that occurs before
pregnancy and during pregnancy continues in the postpartum period in approximately
90% of cases. Pregnant teenagers are at greater risk of abuse, but abused adult
women sustain more physical injuries.
Violence is a marker for other pregnancy risks such as tobacco, alcohol, and substance
abuse; gynecological infection; unmarried or unpartnered status; unintended pregnancy;
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rapid repeat pregnancy (pregnant within 24 mo of prior pregnancy); psychiatric disease;
and emotional problems.
In reported cases, 95% of perpetrators are male intimate partners of the abused
women. Risk factors associated with abusing a partner are drug, alcohol, and tobacco
abuse; witnessing abuse as a child; and beliefs supportive of patriarchy. The causes of
domestic violence are unclear. Most research has indicated that issues of power and
control are central to abuse. Researchers identified 4 themes:




Jealousy toward the fetus
Pregnancy-specific violence not directed toward the fetus (stress caused by
pregnancy)
Anger toward the fetus (undesired pregnancy)
A "business as usual" mentality (continued violence to the partner)
A link exists between violence toward women and violence toward children. An
estimated 50% of perpetrators also abuse their children. The malignant environment
also spills over to the victims of abuse; in one study, 28% of battered women
demonstrated violent behavior toward their children. In a completion of the cycle,
juveniles who are incarcerated for aggression have an increased likelihood of having
sustained perinatal trauma.
Symptoms and presentation
Injuries and effects occur to both mother and fetus and range from violent behavior,
depression, and grief to crime, severe injury, and death. Domestic violence accounts for
20% of violent crimes to women, and at least 30% of female murder victims are killed by
their partner.
The leading cause of maternal death in the United States is trauma. Approximately 3663% of these deaths are caused by homicide. Repetitive blunt or weapon trauma may
be seen. The face, head, and extremities are frequent sites. During pregnancy, the
trauma inflicted may be directed toward the breasts, abdomen, or genitals. Violence
should be classed as severe if it results in injuries due to choking, hitting, kicking, or
weapons. Damage to the spleen, liver, diaphragm, and uterus may occur.
Severe injuries caused by violence can cause uterine contractions, preterm delivery,
and placental abruption. Persistent abuse throughout pregnancy is associated with
IUGR, preterm delivery, and an increased incidence of miscarriage; these effects may
be due to severe environmental stress. More rarely, direct fetal injury occurs, and
results include soft tissue injury, organ damage, skull fracture, and other fractures.
Violence in relationships has recently been linked to rapid repeat pregnancy, especially
in teenagers, which is associated with an increased risk of delivering prematurely,
having an infant that is small for gestational age, and miscarrying. In fact, these women
have a 22.6-fold increased chance of miscarriage.
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More typically, injuries are multiple, in various stages of healing, and inconsistent with
the patient's story. If a patient's explanation of injuries does not match clinical findings,
the clinician must be alert to the possibility of abuse. Protective bruising from a
defensive posture is often seen on the extremities.
Patients may present with complaints of overt abuse, or they may present with
nonspecific symptoms. Overt presentations include chronic pelvic pain, STDs, or
complications of pregnancy. Late registration to care, loss to obstetrical care, and poor
weight gain are particularly frequent in pregnant women who are abused. The abused
woman may present with vague somatic complaints including nausea, headaches,
pelvic pain, fatigue, and depression. As many as one third of women presenting to
emergency departments are victims of abuse, yet as few as 1 in 20 abused women is
identified by physicians.
Intervention
Multiple studies and summaries of experience have demonstrated a need for consistent
screening to identify abused women. Optimal results are obtained when direct questions
are addressed to the patient in a completely confidential manner, excluding children
who can speak and family-member translators. Women should be screened multiple
times during pregnancy. Violence occurs across all socioeconomic classes, and no
woman should forgo screening for this or any other reason.
Physicians often express frustration in dealing with the issue of domestic violence; they
may fear loss of control during the interview, and they may feel as though they are
"opening a Pandora's box.? Yet, when performed in a confidential manner by a
physician, screening works best. Not all abuse victims are able or willing to take the
next step (escape from the situation) after the first contact. All providers who care for
pregnant women should be aware of and act to complete their responsibilities toward
abused women.
As is the case with many psychosocial and environmental risks during pregnancy, the
provider must work within a political and social milieu. The immediate safety and
medical status of the patient should be paramount. Documentation should be thorough
and complete, and the clinician should use the patient?s own words when possible. A
complete history of the patient?s relationships, abuse, and living situation should be
included in addition to her obstetrical and gynecological history. Body maps and
photographs should be included as appropriate, and forensic kits should be used in
cases of sexual assault.
The physician should provide a complete report, even though insurance companies
have previously used this information to discriminate against victims of abuse when
providing coverage or benefits. This discrimination is now illegal by state law in more
than 50% of states, and it is illegal according to a federal law concerning insurance
discrimination.
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Because suspicion of revelation may cause the abuser to escalate violence,
confidentiality is of the utmost importance. Items covered by confidentiality should
include all correspondence, telephone calls, bills, and contacts with the patient.
Violence is increasingly recognized as an epidemic within our country. Efforts to remove
the stigma from victims of abuse are underway, but these efforts will not succeed
without support at every point of entry to medical care.
If you are a victim of domestic violence or would like to seek help for someone else,
please contact the National Domestic Violence Hotline at (800) 799-SAFE. The TDD
number for persons with hearing impairment is (800) 787-3224.
Depression and other psychiatric illnesses
Mood disorders, the most prevalent of which is depression, are common in this country,
and a proportion of every physician?s patients are affected. Some recent reviews
estimate that as many as 40% of women have an episode of clinical depression in their
lifetime. One in every 8 people is clinically diagnosed with depression, and this rate is
almost doubled for women.
Risk of depression increases with age. Although pregnancy is usually a time of joyful
anticipation, it is also a stressor for many women. In the United States, depression is
both overtreated and undertreated, and only 1 in 5 patients is treated appropriately.
Depression is often underrecognized during pregnancy. The immediate postpartum
period (the puerperium) is a particularly high-risk time for very severe depression and
even psychosis.
In an effort to avoid risks from psychiatric medications, many women suspend their
medication when attempting conception or they discontinue their medication when they
discover they are pregnant. Yet, as is the case with seizure, their pregnancies may be
at risk from their illness. In particular, bipolar disorder (manic depression) may be risky
for both mother and child because mania severely impairs judgment and suicide rates
are high in the depressive part of the cycle. Worse, suspension of effective medication,
especially lithium, may render the medication ineffective when resumed.
Depression screening is reasonable. Long surveys have been simplified using
questions that address the most frequent defining symptoms. A diagnosis of major
depression can be made when 5 of the following 8 criteria are met:
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Depressed mood the majority of the day
Loss of almost all or all pleasure from normally pleasant activities
Significant weight change
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue, loss of energy
Reduced concentration, diminished ability to think
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
Recurrent thoughts of death, suicidal thought with or without plan to act
Duration of symptoms must exceed 2 weeks, and the first or second symptom listed
must be present. In addition, the diagnosis may be in question if the symptoms are
within 2 months of significant personal loss or if the clinician believes the symptoms are
due to medication use or other medical conditions.
Similar to domestic violence, somatic complaints are frequent in patients with
depression. Some complaints are specific to obstetricians and gynecologists. These
symptoms include chronic vulvar pain, itching, or burning without clinical cause; chronic
pelvic or genitourinary pain; prolonged depressed mood after a procedure or event;
severe premenstrual symptoms; and multiple somatic complaints that do not match
known etiologies.
Although women are more frequently clinically depressed and make more attempts at
suicide, men complete more suicide attempts. Isolation or exclusion from society is an
important factor that exacerbates depression; isolation is often seen in elderly,
immigrant, and LGBT populations. LGBT teenagers, in particular, are at risk for suicide,
and they have a suicide rate that is significantly higher compared to that of their peers.
The postpartum period is a time of particular risk. The reasons for this are not fully
understood. Recent studies point to the possibility that neurosteroid molecules,
specifically brain progesterone, may be involved. Pregnancy is a time of very high
estrogen and progesterone levels. At delivery, progesterone levels plummet. At least
10% of women have situational depression, which is also known as the postpartum
blues. If the blues deepen into full depression within 6 months of delivery (as indicated
by the aforementioned criteria), postpartum depression is the diagnosis.
Approximately 1-4 of every 1000 new mothers have the most extreme form, postpartum
psychosis. Postpartum psychosis is a serious illness that is characterized by a
disconnection from reality, severe disorientation, psychotic delusions, and/or paranoia.
Postpartum psychosis has a high risk of recurrence in subsequent pregnancies,
especially when the interval between pregnancies is short. The patient and the
patient?s offspring may be at risk of suicide or homicide.
Intervention
Depression screening should be performed before conception or during the first
trimester. Patients with risk factors should have the topic revisited periodically.
Continuation of any therapeutic counseling is a given. However, medications may
require adjustment or discontinuation, and the decision must be made on a case-bycase basis.
Just as substance abuse carries a significant stigma, so too does mental illness.
Sensitivity and openness are keys to caring for this very large group of patients.
Depression serves as a model for caring for patients with other mental disorders, such
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as anxiety, impulse control disorder, personality disorders, obsessive-compulsive
disorder, and schizophrenia.
MEDICAL CONDITIONS WITH ENVIRONMENTAL COMPONENTS
Schizophrenia
While treatment or nontreatment of active schizophrenia is a risk to the pregnancy,
intriguing evidence exists that environmental factors during pregnancy may affect the
risk of schizophrenia for the child. In fact, the concordance for development of
schizophrenia in monozygotic twins is only 50%. The genes involved in the inheritance
of schizophrenia are thought to confer a sensitivity to developing the disease. Exposure
to environmental triggers also must occur.
Season of birth is one such factor. People born in the late winter have higher rates of
schizophrenia, schizoaffective disorder, major depression, and manic depression
(bipolar disorder). In the Northern Hemisphere, the increase is observed in births that
occur from December to May, with peaks in January and February. This effect is
observed worldwide; July, August, and September births in the Southern Hemisphere
demonstrate the same effect. This may be because infectious illnesses in late winter
alter the fetal environment or are directly involved in triggering the illness.
Children with CNS infections have higher rates of schizophrenia later in life. Influenza
and coxsackieviruses may be the culprits because the increased risk is 5-fold for
children of infected mothers. In one study, schizophrenia was associated with exposure
to influenza at 20-24 weeks? gestation for female fetuses. In addition, neonatal
meningitis due to coxsackievirus B was associated with a high rate of later
schizophrenia in a small group studied in Japan. Some studies, but not all, have found
increased rates of schizophrenia in cohorts born in epidemic years. Peak vulnerability
appears to occur during the second trimester.
Persons with schizophrenia often have elevated levels of antibodies against herpes and
cytomegalovirus. A marker for autoimmune disease, HLA-A9, may implicate a breach of
the blood-brain barrier during CNS infection that leads to a subsequent attack on the
brain by the body's own immune system. Third-trimester complications, especially
preeclampsia, and delivery complications also may be factors. Preeclampsia, which
leads to hypoxia, is associated with a 9-fold increased risk for schizophrenia. The level
of difficulty during birth correlates with the severity of later ventricular widening in
offspring with schizophrenia.
Birth in a crowded urban environment is also associated with schizophrenia. Whether
this is attributable to facilitated transmission of disease in population-dense cities, family
stress caused by the environment, or some other factor is unknown.
In summary, both genetic and environmental components must occur in order for an
individual to develop schizophrenia.
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Intervention
Pregnant women with risk factors should be counseled about their status. Potential risk
factors include a family history of schizophrenia, a personal history of schizophrenia, an
increased risk for infection, and an increased risk for preeclampsia. Women who will be
in their second or third trimester during influenza season should be vaccinated. Prenatal
influenza is known to cause fetal death, preterm delivery, low birth weight, and brain
damage.
Asthma
Asthma has been increasing in incidence and severity throughout the developed world.
Asthma is a disease of altered immune cell function in which inflammation of the small
airways results in air trapping and reduced emptying of the lungs. An association has
been recognized between generalized allergies (atopy, in which hives and allergic
reactions occur even in response to allergens that are tolerated by most people) and
asthma. In both illnesses, the immunoglobulin E (IgE) system is activated. Infants and
children without asthma switch from the IgE antibody inflammatory system (Th-2
system) to a cell-mediated cytotoxic system (Th-1 system). Persons with asthma persist
in a high-IgE, strong-inflammatory state.
Of course, the situation is never this simple. The cytotoxic killer-cell system is inimical to
pregnancy, and pregnancy shifts the woman's body back to the humoral antibodydominant state while maintaining an excellent tolerance to the antigenically distinct
fetus. Also, in normal, atopic, and asthmatic individuals, the cytotoxic system can
activate the humoral inflammatory system under certain circumstances. In order to
mature and switch systems from Th-2 to Th-1, healthy children must be infected with
serial upper respiratory infections. This allows them to encounter many different
antigens and become tolerant to them.
In a similar fashion, appropriate timing of presentation of food allergens usually
produces tolerance, not allergy, to foods. Important windows of time may exist during
which feeding the wrong food causes the child to develop an allergy to the substance.
No food allergens have been connected with the development of asthma. In addition, no
maternal diet has been correlated with asthma.
Maternal smoking is irrefutably associated with asthma, reduced small airway size, and
decreased pulmonary function in both asthmatic and nonasthmatic offspring. Thus,
although allergic states and asthma have roots in events that occur during pregnancy,
only asthma may be ameliorated or prevented by the cessation of a specific maternal
factor: smoking.
Intervention
Another definitive benefit of quitting smoking is the prevention of asthma.
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Hypercholesterolemia and hyperlipidemia
Coronary artery disease (CAD) is a prominent morbidity for people of middle age. The
roots of this disease are variable and often multifactorial. Recently, screening tests have
been developed for detecting increased risk of early CAD. Many ethical concerns have
been raised about labeling these screen-positive patients as high-risk individuals. Fear
exists that insurance or workplace discrimination will occur. Avoid blanket labeling of
people with risk factors because not all high-risk individuals develop the disease.
Important interactions between environmental and genetic factors occur in the causation
of CAD.
One particular form of early CAD, familial hypercholesterolemia (FH), is an autosomal
dominant disease with an incidence of heterozygosity of 1 in 500 persons. The gene
mutation causes a defective low-density lipoprotein (LDL) receptor, which results in
elevated LDL levels in the majority of patients. Instead of elevated LDL levels, some
patients have a defect in apoprotein B, with a similar outcome. Evidence of disease
occurs in the second decade of life. Efforts to lower lipid levels have a huge impact on
the course of the disease; however, drugs are far more likely to be needed in patients
with FH. Genetic testing can identify FH heterozygotes. Unlike sickle cell anemia, in
which a single mutation in a single gene is the cause, FH is caused by many different
mutations at a few chromosomal hot spots. The frequency of FH (1 in 500 persons)
suggests that it should be part of prenatal screening.
Intervention
Although FH is not caused by the fetal environment, early interactions with the
environment are significant. Environmental alteration is important for the whole family
because both the child and the heterozygote parent are often affected. In contrast,
phenylketonuria, which is screened for in most locations, affects far fewer individuals.
Mothers with a personal or family history of early heart disease should be offered
testing.
Cholestasis of pregnancy
Many diseases are worsened or improved during pregnancy, but intrahepatic
cholestasis of pregnancy (ICP) is a disease that appears in the mother solely because
of the environment produced by her pregnancy.
ICP is an accumulation of bile acid metabolites during late pregnancy, usually the third
trimester. It is characterized by fierce itching (pruritus). Mild conjugated bilirubin
increases are observed in some patients, but outright jaundice is rare. The key to
diagnosis is that liver dysfunction seldom occurs. ICP usually resolves by delivery, but it
often recurs in later pregnancies. It is not a danger to the mother unless resins, such as
cholestyramine, are administered and a vitamin K deficit results in abnormal bleeding.
However, the fetus can be affected. The rates of stillbirth, preterm delivery, and
perinatal morbidity are slightly higher.
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ICP must be distinguished from more severe liver diseases, such as preeclampsia, fatty
liver disease, and gallbladder/bile tract disease. ICP has an unknown etiology, but
recent research suggests that a defect in sex steroid metabolism is expressed when
certain environmental conditions occur. During pregnancy, both the liver and placenta
process steroids and flood the bloodstream with metabolites. Metabolites of both
estrogen and progesterone are being studied. In women with ICP, synthesis and
conjugation of bile acids are unimpaired, but excretion is hampered, which leads to a
buildup of bile acids in the blood. In normal pregnancies, progesterone metabolites are
sulfated and excreted in bile. In ICP pregnancies, progesterone metabolites accumulate
in the serum.
Intervention
ICP is currently a diagnosis of exclusion, although if consistent genetic characteristics
can be determined, a genetic diagnostic test might be developed. Treatment with
ursodeoxycholic acid is effective and improves excretion of metabolites and bile acids.
Type 2 diabetes
Maternal hyperglycemia is clearly correlated with a number of perinatal problems, such
as shoulder dystocia, macrosomia, and slower development of fetal lung maturity.
Fetuses exposed to hyperglycemia are now clearly recognized as having higher-thanexpected rates of obesity, diabetes, and impaired glucose tolerance.
The genetic component is significant, especially in those with type 2 diabetes, but an
environmental component is also present. Some studies have shown that children born
to mothers with gestational diabetes have higher rates of obesity and impaired glucose
tolerance compared to their siblings who were born previous to the mother?s
gestational diabetes.
The risk to fetuses caused by hyperglycemia is a continuous variable, with no threshold.
Even levels of hyperglycemia insufficient to cause a diagnosis of overt gestational
diabetes pose a risk to the fetus. Effects may include congenital anomalies,
macrosomia, and difficult delivery.
Intervention
No consensus has been reached among obstetricians on appropriate screening for
diabetes and gestational diabetes. Multiple standards exist and are considered
acceptable. Because the effects of gestational diabetes and hyperglycemia are a
smooth dose-response curve without a threshold, no matter what cut-off point is
chosen, either too many people will be treated or some hyperglycemia will remain
unmanaged.
Nonetheless, all prenatal programs should have a consistent plan for screening,
counseling, and managing hyperglycemia of all types. An extra effort should be made to
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screen pregnant women with risk factors before week 30 because all interventions are
effective during the last trimester. The best plan may be to use a 2-stage screening
process. First, identify high-risk pregnancies by one screening method; then, use a
strict, high-threshold standard as a basis for diagnosis of gestational diabetes.
Cleft lip and palate
Central-line craniofacial defects occur during the first trimester. Some defects and
groupings of defects are separate genetic or environmental entities. Other defects are
part of larger congenital syndromes such as trisomy 18. Sex differences also exist. Cleft
lip with or without cleft palate affects males more often than females. Cleft palate affects
far more females than males. Twin studies show a large genetic component; fully 70%
of monozygotic twins both develop a given defect. Despite these genetic factors, clear
environmental correlates are also present.
In Denmark, a large population registry for cleft palate defects has been studied since
1932. Much of what is understood about the defect comes from this population.
Ongoing efforts are being made to do wider, global studies to improve the clinical
applicability of the results.
Important environmental correlates that have been identified include antiepileptic drugs,
maternal smoking, folic acid antagonists, and retinoic acid (vitamin A). The first 3 of
these factors may involve folate pathways. Retinoic acid is directly involved in pattern
formation in the embryo. Denmark has a high rate of vitamin A intake by mothers during
the first trimester due to wide consumption of liver paste products.
Intervention
The example of cleft lip and palate shows that anomalies that might typically be
considered solely genetic in origin have a measurable environmental component.
Appropriate vitamin and micronutrient consumption should be addressed, preferably
during preconception counseling. Supplementing women with deficiencies and
preventing overdose helps prevent anomalies.
REFERENCES:
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American College of Obstetricians and Gynecologists: Domestic Violence. ACOG
Educational Bulletin, No. 257. Chicago, Ill: American College of Obstetricians and
Gynecologists; December 1999.
Arbuckle TE, Sever LE: Pesticide exposures and fetal death: a review of the
epidemiologic literature. Crit Rev Toxicol 1998 May; 28(3): 229-70
Brent RL: Reproductive and teratologic effects of low-frequency electromagnetic
fields: a review of in vivo and in vitro studies using animal models. Teratology
1999 Apr; 59(4): 261-86
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Brent RL: Utilization of developmental basic science principles in the evaluation
of reproductive risks from pre- and postconception environmental radiation
exposures. Teratology 1999 Apr; 59(4): 182-204
Buchanan TA, Kjos SL: Gestational diabetes: risk or myth? J Clin Endocrinol
Metab 1999 Jun; 84(6): 1854-7
Christensen K: The 20th century Danish facial cleft population--epidemiological
and genetic-epidemiological studies. Cleft Palate Craniofac J 1999 Mar; 36(2):
96-104
Cunningham FG, McDonald PC, Norman PG, eds: Williams Obstetrics. 20th ed.
Stamford, Conn: Appleton & Lange; 1997.
Datner EM, Ferroggiaro AA: Violence during pregnancy. Emerg Med Clin North
Am 1999 Aug; 17(3): 645-56, vi
Fattibene P, Mazzei F, Nuccetelli C, Risica S: Prenatal exposure to ionizing
radiation: sources, effects and regulatory aspects. Acta Paediatr 1999 Jul; 88(7):
693-702
Fry LR: Prenatal screening. Prim Care 2000 Mar; 27(1): 55-69
Galtier-Dereure F, Boegner C, Bringer J: Obesity and pregnancy: complications
and cost. Am J Clin Nutr 2000 May; 71(5 Suppl): 1242S-8S
Geeze DS: Pregnancy and in-flight cosmic radiation. Aviat Space Environ Med
1998 Nov; 69(11): 1061-4
Goldman LR: New approaches for assessing the etiology and risks of
developmental abnormalities from chemical exposure. Reprod Toxicol 1997 MarJun; 11(2-3): 443-51
Gonzalez MJ, Schmitz KJ, Matos MI, et al: Folate supplementation and neural
tube defects: a review of a public health issue. P R Health Sci J 1997 Dec; 16(4):
387-93
Haglund LJ, Britton JR: The perinatal assessment of psychosocial risk. Clin
Perinatol 1998 Jun; 25(2): 417-52
Hanrahan JP, Halonen M: Antenatal interventions in childhood asthma. Eur
Respir J Suppl 1998 Jul; 27: 46s-51s
Jacoby M, Gorenflo D, Black E, et al: Rapid repeat pregnancy and experiences
of interpersonal violence among low-income adolescents. Am J Prev Med 1999
May; 16(4): 318-21
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Florida Heart CPR*
Pregnancy Risks Assessment
1. The most feared mutagen and teratogen in current times is
a. Alcohol
b. Cocaine
c. Radiation
d. Chemotoxins
2. Documented effects of radiation include intrauterine lethality, organ malformation,
and
a. solid tumors
b. later-onset leukemia
c. mental impairment
d. all of the above
3. ________ effects are usually intrauterine, often postconceptual, effects involving
damage to growing and pattern-forming cell populations.
a. Stochastic
b. Adverse
c. Antepartum
d. Deterministic
4. _______ effects do not show a threshold, and they occur in the later years of the
exposed individual’s life.
a. Stochastic
b. Adverse
c. Antepartum
d. Deterministic
5. _______is ionizing radiation by heavy particles, such as protons and helium
nuclei, that originate outside the earth.
a. Nuclear radiation
b. Solar radiation
c. UV radiation
d. Cosmic radiation
6. Endocrine disruptors are chemicals that can
a. mimic hormones
b. occupy hormonal receptors
c. trigger inappropriate hormone responses in the body
d. all of the above
7. ________ accumulates in the food chain, especially in fish, and it causes
neurological damage in human infants exposed in utero.
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37
a.
b.
c.
d.
Iron
Mercury
Helium
Lead
8. Study data suggest an increased risk of fetal death associated with _____in
general and with maternal employment in agricultural industries.
a. Plants
b. Pesticides
c. Industrial work
d. Bug spray
9. Epilepsy is a very common disorder that affects women of reproductive age. The
risk for malformation ______with use of anticonvulsants, and a few distinct
syndromes are observed.
a. Doubles
b. Triples
c. Quadruples
d. Increases 5 fold
10. Strong evidence from prospective studies demonstrates that _____ deficiency is
associated with neural tube defects and spina bifida.
a. Folate
b. Iron
c. Vitamin C
d. Mercury
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