Teratogens and critical periods — MCQs

10 questions

A 31-year-old G1P0000 presents to her obstetrician for her first prenatal visit after having a positive home pregnancy test one week ago. She states that her last menstrual period was 8 weeks ago. The patient has a past medical history of type I diabetes mellitus since childhood and is on insulin. Her hemoglobin A1c two weeks ago was 13.7%. At that time, she was also found to have microalbuminuria on routine urinalysis, and her primary care provider prescribed lisinopril but the patient has not yet started taking it. The patient’s brother is autistic, but family history is otherwise unremarkable. At this visit, her temperature is 98.6°F (37.0°C), blood pressure is 124/81 mmHg, pulse is 75/min, and respirations are 14/min. Exam is unremarkable. This fetus is at increased risk for which of the following?

A 27-year-old P1G1 who has had minimal prenatal care delivers a newborn female infant. Exam reveals a dusky child who appears to be in distress. Her neck veins are distended and you note an enlarged v wave. She has a holosystolic murmur. Following echocardiogram, immediate surgery is recommended. For which of the following conditions was the mother likely receiving treatment during pregnancy?

A 26-year-old woman with poor prenatal care and minimal antenatal screening presents to the emergency department in labor. Shortly thereafter, she delivers a baby girl who subsequently demonstrates symptoms of chorioretinitis on examination. A series of postpartum screening questions is significant only for the presence of multiple cats in the mother’s household. The clinical team orders an enhanced MRI examination of the infant’s brain which reveals hydrocephalus, multiple punctate intracranial calcifications, and 2 sub-cortical ring-enhancing lesions. Which is the most likely diagnosis?

A 28-year-old female in the 2nd trimester of pregnancy is diagnosed with primary Toxoplasma gondii infection. Her physician fears that the fetus may be infected in utero. Which of the following are associated with T. gondii infection in neonates?

A 32-year-old primigravid woman with a history of seizures comes to the physician because she had a positive pregnancy test at home. Medications include valproic acid and a multivitamin. Physical examination shows no abnormalities. A urine pregnancy test is positive. Her baby is at increased risk for requiring which of the following interventions?

A 32-year-old G2P0A1 woman presents at 36 weeks of gestation for the first time during her pregnancy. The patient has no complaints, currently. However, her past medical history reveals seizure disorder, which is under control with valproic acid and lithium. She has not seen her neurologist during the past 2 years, in the absence of any complaints. She also reports a previous history of elective abortion. The physical examination is insignificant. Her blood pressure is 130/75 mm Hg and pulse is 80/min. The patient is scheduled to undergo regular laboratory tests and abdominal ultrasound. Given her past medical history, which of the following conditions is her fetus most likely going to develop?

During development, a fetus is found to have incomplete fusion of the neural tube. Which of the following structures would most likely be affected by this developmental defect?

An investigator is studying the effects of an antihypertensive drug during pregnancy. Follow-up studies show that the drug can adversely affect differentiation of the ureteric bud into its direct derivatives in fetuses exposed during the first trimester. Which of the following structures is most likely to develop incorrectly in the affected fetus?

A 23-year-old man comes to the physician for evaluation of decreased hearing, dizziness, and ringing in his right ear for the past 6 months. Physical examination shows multiple soft, yellow plaques and papules on his arms, chest, and back. There is sensorineural hearing loss and weakness of facial muscles bilaterally. His gait is unsteady. An MRI of the brain shows a 3-cm mass near the right internal auditory meatus and a 2-cm mass at the left cerebellopontine angle. The abnormal cells in these masses are most likely derived from which of the following embryological structures?

Q10

Shortly after delivery, a female newborn develops bluish discoloration of the lips, fingers, and toes. She was born at term to a 38-year-old primigravid woman. Pregnancy was complicated by maternal diabetes mellitus. Pulse oximetry on room air shows an oxygen saturation of 81%. Echocardiography shows immediate bifurcation of the vessel arising from the left ventricle; the vessel emerging from the right ventricle gives out coronary, head, and neck vessels. An abnormality in which of the following developmental processes most likely accounts for this patient's condition?

Teratogens and critical periods US Medical PG Practice Questions and MCQs

Question 1: A 31-year-old G1P0000 presents to her obstetrician for her first prenatal visit after having a positive home pregnancy test one week ago. She states that her last menstrual period was 8 weeks ago. The patient has a past medical history of type I diabetes mellitus since childhood and is on insulin. Her hemoglobin A1c two weeks ago was 13.7%. At that time, she was also found to have microalbuminuria on routine urinalysis, and her primary care provider prescribed lisinopril but the patient has not yet started taking it. The patient’s brother is autistic, but family history is otherwise unremarkable. At this visit, her temperature is 98.6°F (37.0°C), blood pressure is 124/81 mmHg, pulse is 75/min, and respirations are 14/min. Exam is unremarkable. This fetus is at increased risk for which of the following?

A. Post-term delivery
B. Oligohydramnios
C. Neural tube defect (Correct Answer)
D. Aneuploidy
E. Neonatal hyperglycemia

Explanation: ***Neural tube defect*** - The patient's **poorly controlled type 1 diabetes mellitus** is evidenced by her **HbA1c of 13.7%**. Uncontrolled maternal hyperglycemia during organogenesis significantly increases the risk for fetal malformations, including neural tube defects due to impaired folate metabolism. - This risk is highest when hyperglycemia occurs during the first 8 weeks of gestation, a period crucial for neural tube closure, which aligns with this patient's presentation at 8 weeks' gestation. *Post-term delivery* - **Uncontrolled maternal diabetes** is typically associated with **macrosomia and polyhydramnios**, which can lead to complications such as **shoulder dystocia, premature rupture of membranes (PROM)**, and often precipitates **earlier induction of labor** rather than post-term delivery. - While exact delivery timing can vary, the direct causal link between uncontrolled diabetes and post-term delivery is not primary; rather, such pregnancies are often managed with earlier interventions. *Oligohydramnios* - Poorly controlled maternal diabetes, particularly type 1, is generally associated with **polyhydramnios** due to fetal polyuria caused by hyperglycemia, not oligohydramnios. - **Oligohydramnios** can be associated with severe **placental insufficiency**, prolonged rupture of membranes, or fetal renal agenesis, none of which are directly indicated by uncontrolled maternal diabetes alone. *Aneuploidy* - The primary risk factor for **aneuploidy** (e.g., Down syndrome) is **advanced maternal age**, which is not present in this 31-year-old patient. - **Maternal diabetes** itself is not a direct risk factor for aneuploidy; genetic factors related to nondisjunction are the main cause. *Neonatal hyperglycemia* - Maternal hyperglycemia leads to fetal hyperglycemia, causing **fetal hyperinsulinemia**. After birth, the neonate's elevated insulin levels, in the absence of maternal glucose supply, result in **neonatal hypoglycemia**, not hyperglycemia. - **Neonatal hyperglycemia** is rare and usually associated with specific genetic defects or administration of excessive glucose postnatally, not maternal diabetes.

Question 2: A 27-year-old P1G1 who has had minimal prenatal care delivers a newborn female infant. Exam reveals a dusky child who appears to be in distress. Her neck veins are distended and you note an enlarged v wave. She has a holosystolic murmur. Following echocardiogram, immediate surgery is recommended. For which of the following conditions was the mother likely receiving treatment during pregnancy?

A. Bipolar disorder (Correct Answer)
B. Hypothyroidism
C. Depression
D. Hypertension
E. Diabetes

Explanation: ***Bipolar disorder*** - The newborn's symptoms, including a **holosystolic murmur**, **distended neck veins** with an **enlarged v wave**, and cyanosis, are highly suggestive of **Ebstein's anomaly**. - **Ebstein's anomaly** is a congenital heart defect strongly associated with maternal **lithium use** during pregnancy, a common treatment for bipolar disorder. *Hypothyroidism* - Maternal hypothyroidism is associated with an increased risk of miscarriage, stillbirth, and neurodevelopmental problems in the child, but not specifically with Ebstein's anomaly. - Treatment for hypothyroidism primarily involves thyroid hormone replacement, which is not linked to this specific cardiac defect. *Depression* - While various antidepressant medications can be taken during pregnancy, none are specifically linked to Ebstein's anomaly. - Maternal depression itself can impact fetal development due to stress, but not typically through this specific congenital heart defect. *Hypertension* - Maternal hypertension is associated with conditions like **pre-eclampsia**, fetal growth restriction, and preterm birth, but not specifically with Ebstein's anomaly. - Antihypertensive medications generally do not cause this specific congenital heart defect. *Diabetes* - Maternal diabetes can lead to **macrosomia**, **hypoglycemia**, and an increased risk of various congenital anomalies, including **ventricular septal defects** and **transposition of the great arteries**. - However, it is not specifically linked to Ebstein's anomaly, which is more characteristic of lithium exposure.

Question 3: A 26-year-old woman with poor prenatal care and minimal antenatal screening presents to the emergency department in labor. Shortly thereafter, she delivers a baby girl who subsequently demonstrates symptoms of chorioretinitis on examination. A series of postpartum screening questions is significant only for the presence of multiple cats in the mother’s household. The clinical team orders an enhanced MRI examination of the infant’s brain which reveals hydrocephalus, multiple punctate intracranial calcifications, and 2 sub-cortical ring-enhancing lesions. Which is the most likely diagnosis?

A. Rubella
B. Syphilis
C. CMV
D. HSV
E. Toxoplasmosis (Correct Answer)

Explanation: ***Toxoplasmosis*** - The triad of **chorioretinitis**, **hydrocephalus**, and **intracranial calcifications** is classic for congenital toxoplasmosis. - The mother's exposure to **cats** (definitive hosts) and poor prenatal care supports the diagnosis of an acute maternal infection with vertical transmission. *Rubella* - Congenital rubella presents with **sensorineural hearing loss**, **cardiac defects** (e.g., patent ductus arteriosus, pulmonary artery stenosis), and **cataracts**, not chorioretinitis and intracranial calcifications. - While it can cause microcephaly, the specific **hydrocephalus** and diffuse calcifications seen here are not typical. *Syphilis* - Congenital syphilis manifests with early symptoms like **hepatosplenomegaly**, **rash**, and **rhinitis**, and later signs such as **Hutchinson's teeth** and **saddle nose**. - **Chorioretinitis** and the specific pattern of **intracranial calcifications** observed are not characteristic features of congenital syphilis. *CMV* - Congenital cytomegalovirus (CMV) often causes **periventricular calcifications**, **microcephaly**, and **sensorineural hearing loss**, but typically not the diffuse punctate calcifications and subcortical ring-enhancing lesions seen in this case. - While chorioretinitis can occur, the overall clinical picture with **hydrocephalus** points away from CMV as the most likely diagnosis. *HSV* - Congenital herpes simplex virus (HSV) infection typically presents with **skin vesicles**, **keratoconjunctivitis**, and encephalitis, often with focal brain lesions. - The lack of skin lesions and the specific pattern of diffuse **intracranial calcifications** and **chorioretinitis** make HSV less likely.

Question 4: A 28-year-old female in the 2nd trimester of pregnancy is diagnosed with primary Toxoplasma gondii infection. Her physician fears that the fetus may be infected in utero. Which of the following are associated with T. gondii infection in neonates?

A. Hutchinson’s teeth, saddle nose, short maxilla
B. Deafness, seizures, petechial rash
C. Hydrocephalus, chorioretinitis, intracranial calcifications (Correct Answer)
D. Patent ductus arteriosus, cataracts, deafness
E. Temporal encephalitis, vesicular lesions

Explanation: ***Hydrocephalus, chorioretinitis, intracranial calcifications*** - These are the classic triad of symptoms (known as the **Sabin triad**) often associated with **congenital toxoplasmosis**. - **Hydrocephalus** results from obstruction of cerebrospinal fluid flow, **chorioretinitis** can lead to vision loss, and **intracranial calcifications** are a hallmark of the infection's impact on the brain. *Hutchinson’s teeth, saddle nose, short maxilla* - These are characteristic features of **congenital syphilis**, not *Toxoplasma gondii* infection. - **Hutchinson's triad** includes Hutchinson's teeth, interstitial keratitis, and sensorineural hearing loss in congenital syphilis. *Deafness, seizures, petechial rash* - While seizures can occur with severe congenital infections, this combination is more suggestive of **cytomegalovirus (CMV)** infection or **rubella**, which can cause petechial rash (blueberry muffin baby) and profound sensorineural deafness. - *Toxoplasma gondii* does not typically cause a petechial rash as a primary symptom. *Patent ductus arteriosus, cataracts, deafness* - This constellation of symptoms is highly characteristic of **congenital rubella syndrome**. - **Cardiac defects** (like patent ductus arteriosus), **ocular abnormalities** (cataracts), and **sensorineural deafness** are classical signs of rubella. *Temporal encephalitis, vesicular lesions* - **Temporal encephalitis** with vesicular lesions, particularly in a neonatal context, is a classic presentation of **congenital herpes simplex virus (HSV) infection**. - *Toxoplasma gondii* can cause encephalitis, but not typically with vesicular lesions or a primary predilection for the temporal lobe in this specific clinical presentation.

Question 5: A 32-year-old primigravid woman with a history of seizures comes to the physician because she had a positive pregnancy test at home. Medications include valproic acid and a multivitamin. Physical examination shows no abnormalities. A urine pregnancy test is positive. Her baby is at increased risk for requiring which of the following interventions?

A. Lower spinal surgery (Correct Answer)
B. Kidney transplantation
C. Arm surgery
D. Cochlear implantation
E. Respiratory support

Explanation: ***Lower spinal surgery*** - Maternal use of **valproic acid** during pregnancy significantly increases the risk of neural tube defects, particularly **spina bifida**, which often requires surgical correction of the lower spine in affected infants. - **Spina bifida** results from the incomplete closure of the neural tube, leading to exposed spinal cord or meninges, and frequently necessitates surgical intervention to prevent further neurological damage and infection. *Kidney transplantation* - While some fetal anomalies can involve the kidneys, **valproic acid** exposure is not primarily associated with renal agenesis or severe kidney malformations requiring transplantation. - Birth defects affecting the kidneys are more commonly linked to genetic syndromes or other teratogens, not specifically valproic acid. *Arm surgery* - **Valproic acid** has been associated with limb defects, but these are typically minor and do not usually directly necessitate extensive arm surgery. - **Phocomelia** (shortened or absent limbs) is more typically associated with **thalidomide** exposure, not valproic acid. *Cochlear implantation* - Although **valproic acid** exposure has been occasionally linked to some congenital anomalies, it is not a primary risk factor for **severe hearing loss** requiring cochlear implantation. - Hearing loss requiring such intervention is more often due to genetic factors, congenital infections, or other specific teratogens. *Respiratory support* - While a variety of congenital conditions can lead to respiratory compromise, **valproic acid** exposure does not specifically cause severe pulmonary hypoplasia or other defects that commonly necessitate prolonged or intense neonatal respiratory support. - Respiratory distress in neonates is often related to prematurity, meconium aspiration, or other direct pulmonary issues.

Question 6: A 32-year-old G2P0A1 woman presents at 36 weeks of gestation for the first time during her pregnancy. The patient has no complaints, currently. However, her past medical history reveals seizure disorder, which is under control with valproic acid and lithium. She has not seen her neurologist during the past 2 years, in the absence of any complaints. She also reports a previous history of elective abortion. The physical examination is insignificant. Her blood pressure is 130/75 mm Hg and pulse is 80/min. The patient is scheduled to undergo regular laboratory tests and abdominal ultrasound. Given her past medical history, which of the following conditions is her fetus most likely going to develop?

A. Neural tube defects (NTDs) (Correct Answer)
B. Intrauterine growth restriction
C. Iron deficiency anemia
D. Trisomy 21
E. Limb anomalies

Explanation: **Neural tube defects (NTDs)** * The use of **valproic acid** during pregnancy is significantly associated with an increased risk of **neural tube defects (NTDs)**, such as spina bifida and anencephaly, in the fetus. * Valproic acid interferes with **folate metabolism**, which is crucial for proper neural tube closure during early fetal development. *Intrauterine growth restriction* * While some medications and maternal conditions can cause **intrauterine growth restriction (IUGR)**, valproic acid and lithium are **not primary causes** of IUGR. * Other factors, such as **placental insufficiency**, severe maternal hypertension, or infections, are more commonly associated with IUGR. *Iron deficiency anemia* * **Iron deficiency anemia** is a common maternal condition in pregnancy, but it is **not a direct fetal outcome** of maternal valproic acid or lithium use. * Fetal anemia might occur due to other causes like **Rh incompatibility** or parvovirus infection. *Trisomy 21* * **Trisomy 21 (Down syndrome)** is a **chromosomal anomaly** caused by the presence of an extra copy of chromosome 21. * It is not related to maternal medication use like valproic acid or lithium; its incidence is primarily correlated with **advanced maternal age**. *Limb anomalies* * Although several teratogenic medications can cause **limb anomalies**, **valproic acid** is more strongly linked to **neural tube defects** and certain **cardiac anomalies**. * **Thalidomide**, for example, is notoriously associated with severe limb malformations.

Question 7: During development, a fetus is found to have incomplete fusion of the neural tube. Which of the following structures would most likely be affected by this developmental defect?

A. Notochord
B. Somites
C. Vertebral bodies
D. Spinal cord and meninges (Correct Answer)

Explanation: ***Spinal cord and meninges*** - Incomplete fusion of the neural tube directly results in defects of the **neural tube closure**, which include the formation of the **spinal cord** and its protective coverings, the **meninges**. [1, 2] - Conditions like **spina bifida** (meningocele, myelomeningocele) are direct consequences of these fusion failures, exposing or abnormally developing the spinal cord and meninges. [1, 2] *Notochord* - The **notochord** is a transient embryonic structure that induces the formation of the neural tube by signaling to the overlying ectoderm; it is not directly formed by the neural tube itself. - While it plays a critical role in neural tube development, its own structural integrity is typically not primarily affected by neural tube fusion defects. *Somites* - **Somites** are blocks of paraxial mesoderm that differentiate into sclerotome (vertebrae and ribs), myotome (skeletal muscle), and dermatome (dermis of the skin). - While somite development is closely coordinated with neural tube formation, incomplete neural tube fusion primarily affects the neural structures themselves, not the somites directly. *Vertebral bodies* - **Vertebral bodies** develop from the sclerotome portion of the somites, which migrate to surround the neural tube and notochord. - While vertebral defects can be associated with severe neural tube defects (e.g., in spina bifida, the vertebral arches may fail to close), the primary defect of incomplete neural tube fusion directly impacts the neural tissue (spinal cord and meninges), with skeletal defects being secondary or associated. [1, 2]

Question 8: An investigator is studying the effects of an antihypertensive drug during pregnancy. Follow-up studies show that the drug can adversely affect differentiation of the ureteric bud into its direct derivatives in fetuses exposed during the first trimester. Which of the following structures is most likely to develop incorrectly in the affected fetus?

A. Collecting ducts (Correct Answer)
B. Proximal convoluted tubule
C. Loop of Henle
D. Bladder
E. Distal convoluted tubule

Explanation: ***Collecting ducts*** - The **ureteric bud** is an outgrowth of the **mesonephric (Wolffian) duct** that directly gives rise to the **collecting ducts**, minor and major calyces, renal pelvis, and ureter. - An adverse effect on the differentiation of the ureteric bud during the first trimester would directly impact the development of these structures, potentially leading to renal dysplasia or collecting system abnormalities. - **Clinical correlation**: ACE inhibitors and ARBs are contraindicated in pregnancy due to their teratogenic effects on fetal renal development. *Proximal convoluted tubule* - The **proximal convoluted tubule** develops from the **metanephric mesenchyme**, not from the ureteric bud. - This structure is part of the nephron proper, which forms when the metanephric mesenchyme is induced by the ureteric bud to differentiate. *Loop of Henle* - The **loop of Henle** also develops from the **metanephric mesenchyme**. - While its formation depends on inductive signals from the ureteric bud, it is not a direct derivative of the ureteric bud itself. *Bladder* - The **bladder** develops from the **urogenital sinus**, which is derived from the ventral part of the **cloaca** after partitioning by the urorectal septum. - Its development is distinct from the derivatives of the ureteric bud, though they are functionally connected. *Distal convoluted tubule* - The **distal convoluted tubule** develops from the **metanephric mesenchyme**. - It is a component of the nephron and connects to the collecting duct but is not a direct derivative of the ureteric bud.

Question 9: A 23-year-old man comes to the physician for evaluation of decreased hearing, dizziness, and ringing in his right ear for the past 6 months. Physical examination shows multiple soft, yellow plaques and papules on his arms, chest, and back. There is sensorineural hearing loss and weakness of facial muscles bilaterally. His gait is unsteady. An MRI of the brain shows a 3-cm mass near the right internal auditory meatus and a 2-cm mass at the left cerebellopontine angle. The abnormal cells in these masses are most likely derived from which of the following embryological structures?

A. Surface ectoderm
B. Neural tube
C. Neural crest (Correct Answer)
D. Notochord
E. Mesoderm

Explanation: ***Neural crest*** - The patient's symptoms (bilateral sensorineural hearing loss, facial weakness, unsteady gait, central masses) along with cutaneous lesions (soft, yellow plaques) are highly suggestive of **Neurofibromatosis type 2 (NF2)**. - NF2 is characterized by **vestibular schwannomas** (acoustic neuromas) and other CNS tumors, which are derived from **Schwann cells**. Schwann cells, along with melanocytes and other peripheral nervous system components, originate from the **neural crest**. *Surface ectoderm* - The surface ectoderm forms structures such as the **epidermis**, hair, nails, and anterior pituitary. - While the skin lesions are present, the primary tumors (schwannomas) are not derived from the surface ectoderm. *Neural tube* - The neural tube gives rise to the **central nervous system** (brain and spinal cord) and motor neurons. - While the tumors affect the brain and cranial nerves, the specific cell type forming schwannomas (Schwann cells) does not originate directly from the neural tube. *Notochord* - The notochord induces the formation of the neural tube and eventually degenerates, contributing to the **nucleus pulposus** of the intervertebral discs. - It is not involved in the pathogenesis or cellular origin of schwannomas. *Mesoderm* - The mesoderm gives rise to connective tissues, blood, bone, muscle, and most internal organs. - While some tumors can have mesodermal origins, schwannomas are neuroectodermal in origin.

Question 10: Shortly after delivery, a female newborn develops bluish discoloration of the lips, fingers, and toes. She was born at term to a 38-year-old primigravid woman. Pregnancy was complicated by maternal diabetes mellitus. Pulse oximetry on room air shows an oxygen saturation of 81%. Echocardiography shows immediate bifurcation of the vessel arising from the left ventricle; the vessel emerging from the right ventricle gives out coronary, head, and neck vessels. An abnormality in which of the following developmental processes most likely accounts for this patient's condition?

A. Alignment of infundibular septum
B. Fusion of endocardial cushion
C. Spiraling of aorticopulmonary septum (Correct Answer)
D. Separation of tricuspid valve tissue from myocardium
E. Division of aorta and pulmonary artery

Explanation: ***Spiraling of aorticopulmonary septum*** - The description of a vessel arising from the left ventricle that immediately bifurcates (pulmonary artery) and a vessel from the right ventricle that gives off coronary, head, and neck vessels (aorta) is characteristic of **transposition of the great arteries (TGA)**. - TGA results from a failure of the **aorticopulmonary septum** to spiral during embryological development, leading to the aorta originating from the right ventricle and the pulmonary artery from the left ventricle. *Alignment of infundibular septum* - Abnormal alignment of the infundibular septum is associated with conditions like **tetralogy of Fallot**, which involves a maligned interventricular septum and a shifted aorta, presenting with a different set of echocardiographic findings. - While also a **cyanotic heart defect**, tetralogy of Fallot's anatomy (e.g., interventricular septal defect, pulmonary stenosis) differs from the described TGA. *Fusion of endocardial cushion* - Failure of fusion of the **endocardial cushions** leads to **atrioventricular septal defects**, which involve defects in both the atria and ventricular septa, and often affect the mitral and tricuspid valves. - These defects typically present with heart failure symptoms and different echocardiographic findings than those described for TGA. *Separation of tricuspid valve tissue from myocardium* - An abnormality in the separation of tricuspid valve tissue from the myocardium is the cause of **Ebstein anomaly**, where the tricuspid valve leaflets are displaced downwards into the right ventricle, leading to tricuspid regurgitation. - Ebstein anomaly is characterized by right atrial enlargement and a largely functional right ventricle, leading to issues with right heart output but not the great artery transposition described. *Division of aorta and pulmonary artery* - The division of the truncus arteriosus into the aorta and pulmonary artery is a normal developmental process, which when complete usually produces the correct great artery connections. However, the exact arrangement of these vessels is determined by the **spiraling of the aorticopulmonary septum**, not just the division itself. - Failure of this division, resulting in a **persistent truncus arteriosus**, would present as a single great artery arising from both ventricles, which is distinct from the two separate but transposed vessels seen in TGA.

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