Chapter 9 Flashcards
___, ___, and ___ are synonymous terms used to describe structural, behavioral, functional, and metabolic disorders present at birth
Birth defect, congenital malformation, and
congenital anomaly
Terms used to describe the study of these disorders are ___ and ___
teratology and dysmorphology
____ occur in approximately 15% of newborns. These structural abnormalities, such as microtia (small ears), pigmented spots, and short ____, are not themselves detrimental to health but, in some cases, are associated with major defects
Minor anomalies - palpebral fissures
Therefore, the critical period for causing most structural birth defects extends from ____
fertilization through the eighth week of gestation
Many ___ occur during formation of structures, for example, during the period of organogenesis that extends from the beginning of the ____
malformations - third to the end of the eighth week of gestation
Although this tenet holds true for many insults to normal development, it is important to note that ___ begins late in the ___ at the blastocyst stage and that a great variety of birth defects can be caused by disruptions in cell signaling during specification of the cranial-caudal and left-right axes
axis formation - first week
___ result in morphological alterations of already formed structures and are
caused by destructive processes. Vascular accidents leading to transverse limb defects and defects produced by amniotic bands are examples
Disruptions
A ___ is a group of anomalies occurring together that have a specific common cause. This term indicates that a diagnosis has been made and that the risk of recurrence is known
syndrome
___ result from mechanical forces
that mold a part of the fetus over a prolonged period. Clubfeet, for example, are caused by compression in the amniotic cavity. often involve the musculoskeletal system and may be reversible postnatally
Deformations
In contrast, ___ is the nonrandom appearance of two or more anomalies that occur together more frequently than by chance alone, but the cause has not been determined. An example is the VACTERL association (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb defects)
association
In 1961, observations by W. Lenz linked limb defects to the sedative ___ and made it clear that drugs could also cross the placenta and produce birth defects
thalidomide
Since that time, many agents have been identified as ___ (factors that cause birth defects)
teratogens
Birth defects due to ___ (German measles) during pregnancy (congenital rubella syndrome) used to be a major problem, but development and widespread use of a vaccine have nearly eliminated congenital malformations from this cause
rubella
Factors determining the capacity of an agent to produce birth defects have been defined and set forth as the ____
principles of teratology
___ and ___ can cause birth defects. Herpes-induced abnormalities are rare, and usually, infection is transmitted to the child during delivery, causing severe illness and sometimes death. Intrauterine
infection with the latter scarring of the skin, limb hypoplasia, and defects of the eyes and central nervous system
Herpes simplex virus and varicella virus
___ is a serious threat. Often, the mother has no symptoms, but the effects on
the fetus can be devastating. The infection can cause serious illness at birth and is sometimes fatal. On the other hand, some infants are asymptomatic at birth but develop abnormalities later, including hearing loss, visual impairment, and intellectual disability
Cytomegalovirus
___ causes ___ following transmission of the virus from an infected mother to her unborn child. Infections late in the first trimester (7 to 12 weeks) are the most likely to harm the fetus, although abnormalities have been observed following infections up to 18 weeks
Zika Virus causes congenital Zika syndrome (CZS)
Zika infection causes a unique pattern of birth defects in affected children including (1) ____ with overlapping cranial sutures, redundant scalp skin, and a prominent occipital bone
(2) thinning of the cerebral cortex with abnormal gyri and subcortical calcification (3) microphthalmia and coloboma
(4) joint contractures (arthrogryposis)
(5) neurological sequelae, including motor and cognitive deficits
severe microcephaly
___ can cause birth defects. Poorly cooked meat; feces of domestic animals, especially cats; and soil contaminated with feces can carry the protozoan parasite Toxoplasmosis gondii. A characteristic feature of this infection is cerebral calcifications
Toxoplasmosis
____ kills rapidly proliferating cells, so it is a potent teratogen, producing virtually any type of birth defect depending on the dose and stage of development of the concepts at the time of exposure
Ionizing radiation
One example is ___, an antinauseant and sleeping pill. In 1961, it was noted in West Germany that the frequency of amelia and meromelia (total or partial absence of the extremities), a rare abnormality that was usually inherited, had suddenly increased
thalidomide
One example is thalidomide, an antinauseant and sleeping pill. In 1961, it was noted in West Germany that the frequency of __ and __ (total or partial absence of the extremities), a rare abnormality that was usually inherited, had suddenly increased
amelia and meromelia
___, an analogue of Vitamin A, has been shown to cause a characteristic pattern of malformations known as the isotretinoin embryopathy
Isotretinoin (Accutane)
Isotretinoin (Accutane), an analogue of ____ has been shown to cause a characteristic pattern of malformations known as the isotretinoin embryopathy
Vitamin A
Isotretinoin (Accutane), an analogue of Vitamin A, has been shown to cause a characteristic pattern of malformations known as the ____
isotretinoin embryopathy
Other drugs with teratogenic potential include the ___, ____, and ____, which are used by women who have seizure disorders
anticonvulsants diphenylhydantoin (phenytoin), valproic acid, and trimethadione
Specifically, trimethadione and diphenylhydantoin produce a broad spectrum of abnormalities that constitute distinct patterns of dysmorphogenesis known as the___ and ___. Facial clefts
are particularly common in these syndromes
trimethadione and fetal hydantoin syndromes
The anticonvulsant ___ increases the risk for several defects, including atrial septal defects (ASD), cleft palate, hypospadias, polydactyly, and craniosynostosis, but the highest risk is for the neural tube defect, spina bifida
valproic acid
Even newer anticonvulsant drugs like ___ increase the risk for cleft lip and/or cleft palate.
Topamax (topiramate)
___ and ___ (major and minor tranquilizers, respectively) are suspected producers of congenital malformations
Antipsychotic and antianxiety agents
The antipsychotics ___ and ___ have been implicated as teratogens. Although evidence for the teratogenicity of this conflicting, an association between the latter and congenital heart defects, especially Ebstein anomaly, is better documented, although the risk is small
phenothiazine and lithium
___ was developed for prevention of the nausea and vomiting experienced following cancer therapy and surgery
but has become a popular treatment, through off-label use, to prevent nausea and vomiting associated with pregnancy
Ondansetron (Zofran)
___ that work as selective ____ including fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro) have been linked by epidemiological studies to multiple birth defects, presumably because of serotonin’s role in establishing the left—
right axis
Antidepressant drugs - serotonin reuptake inhibitors (SSRIs)
___ such as ___, ___, and ___ are used to treat severe pain, and both their use and abuse have been increasing in recent years
Opioid medications - codeine, hydrocodone, and oxycodone
___ is an immunosuppressant drug used to prevent rejection in organ transplant patients. Use of the drug in pregnancy has resulted in spontaneous abortions and birth defects, including cleft lip and palate, microtia (small ears), microcephaly, and heart defects
Mycophenolate mofetil (MMF)
____ that inhibit ___ produce growth retardation, renal dysfunction, fetal death, and oligohydramnios if exposures occur during the second or third trimester. The effects of exposure to these compounds in the first trimester are less clear
Antihypertensive agents
angiotensin-converting enzyme (ACE) inhibitors
The ___ is teratogenic. Infants born to mothers with first-trimester exposures typically have skeletal abnormalities,
including nasal hypoplasia, abnormal epiphysis in their long bones, and limb hypoplasia. In contrast, the anticoagulant ___ does not appear to be teratogenic
anticoagulant warfarin - heparin
For example, the incidence of ___ is estimated to be 2 to 9 infants per 1,000 births, whereas that of ____ is 24 to 48 infants per 1,000 births
fetal alcohol syndrome (FAS) - fetal alcohol spectrum disorder (FASD)
___ use has been linked to premature labor, intrauterine growth retardation, and spontaneous abortion. Also, malformations of the heart, genitourinary
system, and brain have been observed in babies whose mothers used cocaine, and there may be long-term effects on behavior. One difficulty in assessing the drug’s effects is the fact that women who use this drug often use other drugs as well, especially alcohol
Cocaine
There is a well-documented association between maternal ___ ingestion and congenital abnormalities, and because of its widespread use, there is a high incidence of alcohol-related birth defects
alcohol
Because alcohol may induce a broad spectrum of defects, ranging from intellectual disability to structural abnormalities of the brain (microcephaly, holoprosencephaly), face, and heart, the term ____ is used to refer to any alcohol-related defects. ____ represents the severe end of the spectrum
fetal alcohol spectrum disorder - Fetal alcohol syndrome
______ refers to cases with evidence of involvement of the central nervous system that do not meet the diagnostic criteria for FAS
Alcohol-related neurodevelopmental disorder (ARND)
The incidence of FAS and ARND together has been estimated to be 1 in 100 live births. Furthermore, ___ is the leading cause of intellectual disability
alcohol
____ has been linked to a number of adverse pregnancy outcomes whether it is smoked or ingested
Marijuana (tetrahydrocannabinol [THC])
____ has been linked to an increased risk for orofacial clefts (cleft lip and cleft palate) and is a moderate risk factor for heart defects, including transposition of the great arteries (TGA), ASD, pulmonary stenosis, and common truncus arteriosus
Cigarette smoking
Evidence from several studies indicates that ____ techniques are associated with an increase in birth defects and that these
rates are higher with intracytoplasmic sperm injection (ICSI) procedures
in Vitro fertilization
____ are exogenous agents that interfere with the normal regulatory actions of hormones controlling developmental processes. Most commonly, these agents interfere with the action of estrogen through its receptor to cause developmental abnormalities of the central nervous system and reproductive tract
Endocrine disrupters
For some time, it has been known that the synthetic estrogen ___, which was used to prevent abortion, raised the incidence of carcinomas of the vagina and cervix in women exposed to the drug in utero
diethylstilbestrol (DES)
___, containing estrogens and progestogens, appear to have a low teratogenic potential. Because other hormones such as DES produce abnormalities, however, use of oral contraceptives should be discontinued if pregnancy is suspected
Birth control pills
Today, ___ are a concern, and numerous studies to determine their effects on the unborn are under way. Decreasing sperm counts and increasing incidences of testicular cancer, hypospadias, and other abnormalities of the reproductive tract in humans, together with documented central nervous system abnormalities (masculinization of female brains and feminization of male brains) in other species with high environmental exposures, have raised awareness ofthe possible harmful effects of these agents.
environmental estrogens
Evidence from several studies indicates that in Vitro fertilization techniques are associated with an increase in birth defects and that these
rates are higher with ____ procedures
intracytoplasmic sperm injection (ICSI)
Mothers with ___, in which the enzyme phenylalanine hydroxylase is deficient or reduced, resulting in increased serum concentrations of phenylalanine, are at risk for having infants with intellectual disability, microcephaly, and cardiac defects
phenylketonuria (PKU)
Factors responsible for these abnormalities have not been delineated, although evidence suggests that altered glucose levels play a role and that ___ is not teratogenic
insulin
Further examination revealed
that the fish contained an abnormally high level
of ___, which was spewed into Minamata Bay and other coastal waters of Japan
by large industries
organic mercury
___ has been associated with increased abortions, growth retardation, and neurological disorders
Lead
For example, supplementation of salt with iodine eliminates intellectual disability and bone deformities resulting from ___
cretinism
____ lowers the incidence of neural tube defects, such as spina bifida and anencephaly, and also re- duces the risk for hyperthermia—induced abnormalities
Folate supplementation
An essential component of all prevention strategies is to initiate interventions ___
prior to conception
Hundreds of children have been born with severe birth defects produced by ____, compounds used for the treatment of cystic acne [isotretinoin [Accutane]]
retinoids [isotretinoin embryopathy]
____ is a factor for an increased risk for some types of structural birth defects, Down syndrome, and new autosomal dominant mutations
Advanced paternal age
The perinatologist has several approaches for assessing growth and development of the fetus in utero, including ____, ____, ____, and ____
ultrasound, maternal serum screening, amniocentesis, and chorionic villus sampling (CVS)
____ is a relatively noninvasive technique that uses high frequency sound waves reflected from tissues to create images. The approach may be transabdominal or transvaginal, with the latter producing images with higher resolution
Ultrasonography
Fetal age and growth are assessed by ___ during the 5th to the 10th weeks of gestation
crown-rump length
After that, a combination of measurements—including the ____ of the skull, femur length, and abdominal circumference—are used
biparietal diameter (BPD)
After that, a combination of measurements—including the biparietal diameter (BPD) of the skull, ____, and _____—are
used
femur length - abdominal circumference
Down syndrome and some other chromosome related abnormalities through a test called ____
nuchal translucency
____, is the preferred method for obtaining fetal blood. The technique can be employed in the 14th week and is accomplished by using ultrasound guidance to insert a needle into the umbilical cord. Blood samples provide cells for rapid cytogenetic analysis and are used for diagnosis of hematological diseases. The technique has a slightly higher incidence of fetal loss than amniocentesis
Cordocentesis, or percutaneous umbilical blood
sampling (PUBS)
___ involves inserting a needle transabdominally or transvaginally into the placental mass and aspirating approximately 5 to 30 mg of villus tissue
CVS
Factors that place women at higher risk include the following:
- Advanced maternal age (35 years and older)
- Previous family history of a genetic problem, such as the parents having had a child with
Down syndrome or a neural tube defect - The presence of maternal disease, such as diabetes
- An abnormal ultrasound or serum screening test
A search for biochemical markers of fetal status led to development of ___
maternal serum screening tests
There are two types of fetal surgeries: ____, whereby the uterus is exposed and opened to operate directly on the fetus; and ___, using small incisions through the mother’s abdominal wall and the uterus
open fetal surgery - fetoscopic surgery
One of the first of these tests assessed serum ___ concentrations
a-fetoprotein (AFP)
