Zofran: Adverse Event Reports Of Birth Defects & Adverse Fetal Outcomes

Monheit Law sent a Freedom of Information Act (FOIA) request to the FDA on April 30, 2015. We requested all the adverse event reports involving Zofran or its active ingredient ondansetron.

“Adverse event reports” are just that – reports of unfavorable health outcomes that physicians believe to be linked to a pharmaceutical product. Doctors are allowed to submit reports of adverse events to the US Food & Drug Administration’s Adverse Event Reporting System. When drug manufacturers receive such reports, they are required to submit them to the FDA. The FDA compiles a database, and uses the information to identify new potential risks associated with a drug.

Eventually, we received two data files, stretching from January 1, 1991 to April 30, 2015. The files contained more than 3,800 pages, and included a total of 8,682 individual adverse event reports. We scoured the data, searching for any adverse event reports involving prenatal exposure to Zofran. Then we compiled a list of every adverse fetal event, from birth defects to spontaneous abortions, associated with Zofran.

Here are the results:

Zofran Birth Defect Adverse Event Infographic

Now that you’ve seen our infographic, feel free to share it using this link: http://zofranlegal.com/wp-content/uploads/2015/07/FOIA-Infographic-1.png.

Monheit Law’s Zofran Birth Defect FOIA Request: A Detailed Look

We found a total of 475 individual adverse event reports (AER) in which fetal exposure to Zofran, or its active ingredient, was linked to an adverse fetal outcome or congenital anomaly (birth defect).

Note that the FDA sent us 8,682 adverse event reports in response to our FOIA request. 475 represents around 5.4% of the total.

Out of those 475 AERs, 21 contained references simply to “congenital anomaly,” without any more specification.

Below, you’ll find a detailed review of the specific congenital abnormalities for which Zofran was a suspected cause. We’ve chosen to break the adverse events down by physiological region, and provided reference numbers so you can look up specific AERs in the FDA data files we received, which are linked below. You can find more information on how to interpret our numbers and AERs in general here.

Page numbers followed by an asterisk (*) can be found in the data file labeled: “Zofran Adverse Event FOIA Results : Branded & Generic Ondansetron.” All other page numbers refer to the file labeled: “Zofran Adverse Event FOIA Results : Generic Ondansetron.”

Congenital Heart Defects & Cardiovascular Abnormalities

170 total references

  • 20 references to an unspecified “congenital heart defect” or “heart disease congenital”

See: 29, 29, 444, 448, 672, 673, 675, 679, 679, 684, 806, 807, 808, 809, 811, 1939, 2239, 762*, 1554*, 3889*

  • 1 reference to an unspecified “cardiac septal defect”

“Cardiac septal defects,” or “hole in the heart” defects, involve cardiac walls that have failed to form properly during early fetal development. Rather than being contained by a continuous surface, blood is allowed to flow from one side of the heart to the other through a perforation.

See: 754

  • 16 references to “atrial septal defect”

A type of cardiac septal defect, atrial septal defect occurs when a hole remains in the wall that would normally separate the heart’s two upper chambers, the atria.

Several studies have found an increase in the risk for atrial septal defect, as well as other cardiac septal defects, associated with prenatal exposure to Zofran.

See: 1133, 1186, 1621, 1874, 1895, 2011, 2098, 2098, 2098, 2099, 2123, 2366*, 3393*, 3569*, 3718*, 3861*

  • 21 references to “ventricular septal defect”

Another cardiac septal defect, ventricular septal defects involve holes in the wall that separates the heart’s lower chambers, or ventricles.

See: 1133, 1186, 1895, 1964, 2098, 2098, 2098, 2099, 2099, 2100, 2100, 2100, 2103, 2104, 2104, 2105, 2105, 2105, 2105, 2165, 2366*

  • 6 references to “atrioventricular septal defect”

This cardiac septal defect can be highly variable from patient to patient, but generally involves a hole at the heart’s center, where the atria on top meet the ventricles below.

See: 1624, 1996, 2005, 2084, 3767*, 3851*

  • 12 references to “cerebral haemorrhage” or “cerebral haemorrhage fetal”

A type of stroke, in which the bursting of an artery within the brain leaks blood into surrounding brain tissue.

See: 1311, 1502, 1503, 1506, 1510, 1511, 1513, 1518, 1519, 1665, 1666, 3087*

  • 1 reference to “anomalous pulmonary venous connection”

This congenital defect occurs when veins that transport blood from the lungs attach to the heart at abnormal locations.

See: 645

  •  3 references to “pulmonary valve stenosis”

A deformity that restricts blood flow from the heart to the lungs, generally caused by a valve that is thicker than normal or fails to open properly. “Stenosis” means “abnormally narrow.” We’ll see that term come up again.

See: 167, 2101, 2123

  • 2 references to “pulmonary artery stenosis”

Similar to pulmonary valve stenosis, except that the abnormal narrowing is present in the pulmonary artery, a blood vessel leading from the heart to the lungs.

See: 1692, 2011

  • 1 reference to “arterial stenosis”

An abnormal narrowing present in an artery. Arteries carry blood away from the heart; while vessels transport blood from the body back to the heart.

See: 3114*

  • 1 reference to “pulmonary artery atresia”

“Atresia” occurs when a passageway in the body is abnormally closed or absent. In most forms of “pulmonary atresia,” a continuous sheet of tissue forms in the place where the pulmonary valve would normally be.

See: 712*

  • 2 references to “pulmonary hypertension”

Hypertension, or high blood pressure, affecting the heart’s right side and arteries in the lungs. Pulmonary hypertension is often a long-term symptom of other congenital heart defects, although one of these reports (2,366*) listed the patient as an 87-day-old baby.

See: 1621, 2366*

  • 2 references to “hypertension neonatal”

Abnormally high blood pressure.

See: 2000*, 3021*

  • 2 references to “patent ductus arteriosus”

The ductus arteriosus is a blood vessel that allows blood to circumvent the lungs while baby’s are in the womb, since their oxygen source comes from maternal blood. After birth, the vessel usually closes after several days. In children born with patent ductus arteriosus, the vessel did not close.

See: 1621, 2366*

  • 2 references to “left ventricular hypertrophy”

Thickening and enlargement of walls in the heart’s left ventricle.

See: 1518, 1665

  • 2 references to “ventricular hypoplasia”

More commonly known as “hypoplastic left heart syndrome,” ventricular hypoplasia occurs when the heart’s left ventricle is severely underdeveloped. In many cases, the condition is fatal.

See: 712*, 1007*

  • 3 references to “coarctation of the aorta”

The aorta, a large blood vessel that transports blood from the heart to the rest of the body, is abnormally narrow.

See: 2101, 2366*, 3569*

  • 1 reference to “bicuspid aortic valve”

The aortic valve, which lies between the heart and the aorta, normally has three flaps, or “leaflets.” In this condition, the valve only has two flaps and can’t open properly.

See: 686*

  • 2 references to “congenital aortic valve incompetence”

Defect in the aortic valve that allows blood to leak back into the left ventricle after being pumped into the aorta.

See: 2366*, 3569*

  • 2 references to “congenital tricuspid valve atresia”

In healthy human hearts, blood flow between the right ventricle and atrium is controlled by the tricuspid valve. Babies born with tricuspid valve atresia don’t have that valve, but a solid sheet of tissue instead.

See: 1271*, 1342*

  • 2 references to “Tetralogy of Fallot”

Four congenital heart defects that often occur together: ventricular septal defect, pulmonary stenosis, right ventricular hypertrophy and an overriding aorta, in which the aortic valve is enlarged.

See: 2101, 738*

  • 1 reference to “mitral valve disease”

The mitral valve is located between the left ventricle and atrium, controlling blood flow between the two chambers.

See: 2366*

  • 2 references to “Shone’s complex”

Four defects on the heart’s left side that occur together: coarctation of the aorta, subaortic stenosis, parachute mitral valve (a disorder that impairs the mitral valve’s ability to function) and supravalvular mitral membrance (an abnormal ring of tissue surrounding the mitral valve).

See: 2366*

  • 1 reference to “dextrocardia”

The heart points toward the body’s right side, rather than to its left as is normal.

See: 686*

  • 1 reference to “Wolff-Parkinson-White syndrome”

An extra electrical pathway leading between the atria and ventricles, often resulting in tachycardia, an abnormally fast heart beat.

See: 686*

  • 1 reference to “arterial thrombosis”

A blood clot in an artery.

See: 865*

  • 4 references to “cardiac flutter”

Also known as “atrial flutter”; an abnormal heart rhythm that begins in the heart’s atria.

See: 1165*, 1181*, 2091*, 2948*

  • 6 references to “cardiac murmur”

An abnormal sound of blood flowing improperly through the heart; often a sign of an underlying cardiac septal defect.

See: 1186, 1715, 3114*, 3393*, 3569*, 3718*

  • 2 references to “fetal arrythmia”

An abnormal heart rhythm. This is a general category that includes many specific rhythm anomalies.

See: 1765*, 3408*

  • 1 reference to “persistent fetal circulation”

Blood flows through a baby’s body differently before birth. This condition occurs when the body fails to change from the circulation patterns before birth to those that normally develop shortly after birth.

See: 1621

  • 1 reference to “peripheral venous disease”

This anomaly involves defects that prevent blood from flowing from the hands and feet to the heart properly.

See: 2224

  • 1 reference to “poor peripheral circulation”

“Peripheral circulation” is blood flow nourishing the body’s extremities and skin.

See: 1007*

  • 5 references to “fetal heart rate abnormal”

These reports also used terms like “fetal heart rate deceleration abnormal” and “heart rate decreased.”

See: 1790, 2017, 702*, 1094*, 2952*

  • 3 references to “bradycardia”

Abnormally slow heart action.

See: 447*, 934*, 3718*

  • 3 references to “heart rate increased”

See: 1964, 1591*, 3408*

  • 5 references to “hypotension”

Abnormally low blood pressure.

See: 743, 1893*, 2031*, 2217*, 2218*

  • 4 references to “platelet count increased”

“Platelets” are a type of blood cell that allow your blood to clot after injury.

See: 366, 1808*, 1812*

  • 2 references to “thrombocytopenia”

Abnormally low platelet count.

See: 2017, 1283*

  • 1 reference to “thrombocytosis”

A disorder in which the body produces too many platelets.

See: 1283*

  • 1 reference to “coagulopathy”

A disorder in which the blood’s ability to clot is impaired.

See: 811*

  • 3 references to “reticulocyte count increased”

“Reticulocytes” are immature red blood cells, that develop in bone marrow.

See: 200, 1089*, 1104*

  • 1 reference to “haemoglobin increased”

“Haemoglobin,” or “hemoglobin” is a protein that allows red blood cells to carry oxygen.

See: 1812*

  • 2 references to “haemoglobin decreased”

See: 2390*, 2859*

  • 1 reference to “blood potassium increased”

Potassium is both a mineral and an electrolyte, that helps maintain the amount of water inside and outside of cells.

See: 1812*

  • 1 reference to “blood potassium decreased”

See: 2015

  • 1 reference to “haematocrit decreased”

“Haematocrit,” or “hematocrit” is the volume percentage of red blood cells in blood.

See: 2390*

  • 1 reference to “naevus flammeus”

A birthmark caused by abnormally stretched capillaries.

See: 3635*

  • 7 references to “haemangioma”

A type of birth mark that often appears red and rubbery, caused by the excessive growth of cells lining arteries and veins.

See: 3284*, 3287*, 3288*, 3289*, 3291*, 3300*, 3616*

Congenital Craniofacial Defects & Disorders

52 total references

  • 7 references to “cleft lip and palate”

In 2012, a team of researchers at Harvard and Boston Universities found that babies exposed to Zofran in utero were 2.37 times more likely to be born with a cleft palate. To learn more about that study and orofacial clefts in general, click here.

See: 1711, 2100, 3343*, 3345*, 3393*, 3417*, 3417*

  • 4 references to “cleft palate”

A split or opening in the roof of the mouth.

See: 1259, 3002*, 3013*, 3383*

  • 2 references to “cleft uvula”

The uvula, the teardrop of flesh hanging above the opening to the throat, is “forked” or split.

See: 3013*, 3718*

  • 3 references to “ankyloglossia congenital”

Tongue is “tethered” to floor of mouth by abnormally long strip of tissue.

See: 1186, 1895, 1033*

  • 3 references to “Pierre Robin syndrome”

A sequence of congenital anomalies that occur together, including cleft palate; “micrognathia,” an abnormally small lower jaw; “retrognathia,” a jaw that is set back; and “glossoptosis,” a tongue that falls back in the throat, obstructing the upper airway.

See: 1032, 1259, 3002*

  • 2 references to “micrognathia”

Abnormally small lower jaw.

See: 1259, 934*

  • 1 reference to “retrognathia”

lower jaw is set further back than normal in relation to the face’s skeletal features.

See: 1259

  • 1 reference to “glossoptosis”

Abnormal retraction of the tongue.

See: 1259

  • 1 reference to “upper airway obstruction”

See: 1259

  • 2 references to an unspecified “congenital nose malformation” or “deformity”

See: 934*, 3389*

  • 3 references to an unspecified “ear malformation”

See: 2123, 718*, 934*

  • 5 references to “deafness congenital”

See: 725*, 795*, 3114*, 3343*, 3345*

  • 3 references to “otitis media chronic”

Chronic middle ear infections; often a symptom of cleft palate.

See: 1711, 3343*, 3345*

  • 1 reference to “otitis media acute”

Acute middle ear infection.

See: 3284*

  • 3 references to “eustachian tube dysfunction”

The eustachian tube links the middle ear to the cavity above the roof of the mouth.

See: 3284*, 3343*, 3345*

  • 1 reference to “low set ears”

Ears are positioned on the head lower than is normal.

See: 3114*

  • 1 reference to an unspecified “skull malformation”

See: 3284*

  • 1 reference to “craniosynostosis”

Joints between skull bones fuse prematurely.

See: 3538*

  • 1 reference to an unspecified “congenital jaw malformation”

See: 3649*

  • 2 references to an unspecified “speech disorder”

In one of these reports (1767*), the affected patient is listed as a two-year-old. On page 3114*, the patient’s age is not listed, but the condition is referred to as “speech disorder developmental.”

See: 1767*, 3114*

  • 2 references to an unspecified “tooth disorder” or “malformation”

See: 3013*, 3718*

  • 2 references to “dental caries”

Tooth decay.

See: 1759*, 1767*

  • 1 reference to “lip ulceration”

See: 1936

Congenital Kidney & Bladder Defects

48 total references

  • 9 references to an unspecified “kidney malformation”

See: 334, 1160, 1175, 1177, 1235, 1874, 777*, 2366*, 3276*

  • 1 reference to an unspecified “congenital renal disorder”

“Renal” refers to the kidney.

See: 467

  • 12 references to “hydronephrosis” or “hydroureter”

Inability to drain urine properly resulting in swollen kidney.

See: 155, 444, 448, 673, 675, 679, 684, 1941, 1946, 1953, 1229*, 3879*

  • 8 references to “metabolic acidosis” or “late metabolic acidosis of prematurity”

Kidneys are unable to remove sufficient amounts of acid from the blood.

See: 460, 463, 471, 504, 583, 643, 658, 1695*

  • 3 references to “renal cyst”

A sac of collected fluid in the kidney.

See: 718*, 762*, 3114*

  • 4 references to “pelvic kidney”

A kidney that remains in the pelvic area, rather than ascending upwards as is normal during fetal development.

See: 1131, 1941, 1946, 1953

  • 1 reference to “kidney duplex”

Two ureters attached to a single kidney.

See: 1941

  • 1 reference to “single functional kidney”

See: 3879*

  • 1 reference to “Bartter’s syndrome”

A genetic mutation that inhibits kidney function.

See: 2015

  • 3 references to an unspecified “urinary tract disorder” or “malformation”

See: 179, 2104, 1229*

  • 2 references to an unspecified “congenital bladder anomaly”

See: 51, 1229*

  • 3 references to “urinary tract infection”

See: 364, 2849*, 2859*

Congenital Respiratory Defects, Anomalies & Disorders

86 total references

  • 2 references to an unspecified “respiratory disorder neonatal”

See: 490, 3383*

  • 1 reference to an unspecified “lung disorder”

See: 1497

  • 24 references to “neonatal respiratory distress syndrome”

Insufficiently developed lungs result in difficulty breathing, apnea (temporary stops in breathing) and shortness of breath. Generally seen in premature babies.

See: 934*, 366, 460, 463, 471, 504, 1695*, 583, 1808*, 622, 1812*, 1812*, 1813*, 1893*, 743, 2031*, 2217*, 2218*, 1692, 3476*, 3601*, 3641*, 3648*, 3814*

  • 17 references to “apnea neonatal”

Intermittent cessation in airflow.

See: 1317, 1502, 1503, 1506, 1507, 1508, 1511, 1515, 1519, 1666, 447*, 702*, 702*, 775*, 934*, 974*, 3718*

  • 2 references to “respiratory arrest”

Complete cessation of normal breathing. Often, but not necessarily, a result of respiratory distress syndrome.

  • 3 references to “neonatal respiratory depression”

Dangerously low breathing rate in newborns.

See: 643, 702*, 3581*

  • 1 reference to “bradypnoea”

Abnormally slow breathing rate.

See: 3718*

  • 3 references to “tachypnoea” or “transient tachypnoea of the newborn”

Temporary rapid breathing caused by excessive fluid in the lungs.

See: 1166, 1007*, 3284*

  • 3 references to “congenital pneumonia”

See: 366, 715*, 795*

  • 2 references to “asthma”

See: 782*, 1223*

  • 1 reference to “obstructive airways disorder”

Or “obstructive lung disease”; a category of respiratory conditions in which breathing is impaired. Asthma is a type of obstructive airways disorder.

See: 2396*

  • 1 reference to “dyspnoea”

Difficult or labored breathing.

See: 1179*

  • 1 reference to “bronchospasm”

Sudden constriction of the passageways that deliver air from the nose or mouth to the lungs.

See: 1179*

  •  3 references to “cyanosis neonatal”

Blue or purple skin coloration due to insufficient levels of oxygen reaching the skin.

See: 366, 1621, 1171*

  • 1 reference to “neonatal hypoxia”

Oxygen levels insufficient to meet physical demands.

See: 273

  • 5 references to an unspecified “congenital diaphragmatic anomaly” or “disorder”

The diaphragm is a sheet of muscle that separates the thoracic cavity, which contains both heart and lungs, from the abdominal cavity beneath. Contraction of the diaphragm draws air into the lungs.

See: 675, 684, 686*, 762*, 3114*

  • 1 reference to “diaphragmatic aplasia”

“Aplasia” refers to the failure of an organ or tissue to develop or function normally.

See: 679

  • 5 references to “pulmonary hypoplasia”

Incomplete development of the lungs.

See: 675, 679, 684, 686*, 2877*

  • 1 reference to “immature respiratory system”

See: 1812*

  • 1 reference to “pneumothorax”

A collapsed lung.

See: 3018*

  • 3 references to “tracheomalacia”

Improper development of the cartilage in the windpipe, or “trachea.”

See: 2101, 1179*, 1179*

  • 1 reference to “bronchopulmonary dysplasia”

Inflammation and scarring in the lungs; generally seen in babies born severely premature.

See: 1342*

  • 2 references to “neonatal aspiration”

A condition in which babies are born with meconium (a baby’s first feces) in the lungs.

See: 1812*, 1812*

  • 2 references to “meconium stain” or “meconium in amniotic fluid”

Generally a sign of neonatal aspiration.

See: 2702*, 3117*

Congenital Gastrointestinal Defects & Disorders

72 total references

  • 3 references to an unspecified “anorectal disorder”

See: 803, 806, 806

  • 1 reference to an unspecified “congenital intestinal malformation”

See: 2099

  • 5 references to an unspecified “gastrointestinal disorder congenital”

See: 2106, 715*, 762*, 777*, 2397*

  • 2 references to an unspecified “abdominal wall anomaly”

See: 2117, 2184

  • 9 references to “gastroschisis”

Portions of the intestine protrude through a hole in the abdominal wall.

See: 444, 448, 672, 673, 675, 679, 679, 684, 1554*

  • 1 reference to “congenital inguinal hernia”

Opening in groin muscles fails to close, allowing intestinal tissues to push forward, creating a bulge.

See: 3114*

  • 7 references to “intestinal obstruction”

Partial or total blockage in the bowels.

See: 1629, 1630, 1631, 1633, 2165, 3261*, 3262*

  • 1 reference to “intestinal fistula”

A “fistula” is an abnormal passage or connection between two body chambers that are not normally connected.

See: 51

  • 5 references to “anal fistula”

See: 806, 808, 808, 809, 811

  • 9 references to “anal atresia”

Anus is either absent or abnormally closed.

See: 51, 467, 806, 807, 808, 808, 809, 811, 2106

  • 1 reference to “haematochezia”

Passage of fresh blood through anus, usually in or with stool.

See: 3395*

  • 2 references to “duodenal atresia”

The first part of the small intestine is either absent or abnormally closed.

See: 168, 996*

  • 1 reference to “large intestinal atresia”

Large intestine is either absent or abnormally closed.

See: 2106

  • 1 reference to “ileal atresia”

The small intestine’s third segment, the “ileum,” is either absent or abnormally closed.

See: 2106

  • 2 references to “abdominal pain”

See: 1763*, 1763*

  • 1 reference to “oesophageal atresia”

The esophagus, or “gullet,” connects the throat to the stomach. In this form of “atresia,” the esophagus ends in a closed pouch, rather than connecting to the stomach.

See: 2107

  • 1 reference to “dysphagia”

Difficulty swallowing.

See: 703*

  • 2 references to “pyloric stenosis”

The valve between the stomach and small intestine is abnormally thick, blocking the passage of food.

See: 2106, 1585*

  • 1 reference to “gastric ulcer”

A break or sore in the lining of intestines, esophagus or stomach.

See: 3395*

  • 6 references to “gastroesophageal reflux disease”

Or “acid reflux”; stomach contents leak from stomach back into esophagus.

See: 1223*, 1585*, 2826*, 2860*, 3395*, 3718*

  • 2 references to “dyspepsia”

Indigestion.

See: 1097*, 2390*

  • 2 references to “enterocolitis”

Inflammation of the small intestine and colon.

See: 1715, 3395*

  • 3 references to “necrotising enterocolitis neonatal”

A disorder in which portions of bowel tissue undergo premature cell death; usually seen in premature infants.

See: 1388*, 1396*, 1399*

  • 1 reference to “necrotising colitis”

Portions of colon tissue undergo premature cell death, or “necrosis.”

See: 1398*

  • 1 reference to “colitis”

Inflammation of the colon.

See: 370

  • 1 reference to “oesophagitis”

Inflammation of esophagus lining.

See: 782*

  • 1 reference to “adenoidal hypertrophy”

Enlarged tonsil.

See: 3718*

Congenital Musculoskeletal Anomalies & Defects

63 total references

  • 5 references to an unspecified “congenital musculoskeletal anomaly”

See: 334, 1874, 2103, 487*, 2634*

  • 9 references to an unspecified “spine malformation” or “deformity”

See: 444, 448, 672, 673, 679, 679, 805*, 1554*, 2366*

  • 7 references to “microcephaly”

Abnormally small head; usually the result of insufficient brain growth.

See: 361, 363, 363, 367, 762*, 3114*, 3213*

  • 3 references to “anencephaly”

Absence of a major portion of the brain, skull and scalp.

See: 1049, 1051, 805*

  • 2 references to “hydrocephalus”

Excessive build-up of cerebrospinal fluid in the brain.

See: 738*, 890*

  • 1 reference to “caudal regression syndrome”

Disorder that impairs the development of the body’s lower half.

See: 467

  • 1 reference to “cauda equina syndrome”

Compression of the “cauda equina,” or “horse’s tail,” a bundle of nerve roots at the spinal cord’s base; can result in paralysis.

See: 2102

  • 1 reference to “hemivertebra”

One half of a spinal vertebra fails to develop fully

See: 467

  • 2 references to “scoliosis”

An abnormal, sideways curvature of the spine.

See: 675, 685

  • 1 reference to “cervical spinal stenosis”

Spinal canal narrows in neck, compressing the spinal cord.

See: 934*

  • 1 reference to “chondrodystrophy”

Improper cartilage development.

See: 934*

  • 2 references to “developmental hip dysplasia”

“Looseness,” or instability of the hip joint.

See: 3343*, 3345*

  • 2 references to “femoral anteversion”

Thigh bone, or “femur,” twists inward.

See: 3343*, 3345*

  • 2 references to “tibial torsion”

Shin bones twist inward.

See: 3343*, 3345*

  • 12 references to “hypertonia”

Abnormal muscle tension; reduces muscle’s ability to stretch.

See: 457, 460, 490, 504, 583, 643, 658, 1099, 1265*, 1695*, 2010*, 2013*

  • 5 references to “hypotonia neonatal” or “congenital muscle absence”

Abnormally decreased muscle tone.

See: 1099, 1621, 725*, 775*, 1223*

  • 1 reference to “muscular weakness”

See: 3284*

  • 3 references to “asthenia”

Abnormal physical weakness.

See: 364, 703*, 934*

  • 1 reference to “myopathy”

Muscle fibers fail to function or function improperly, generally resulting in pronounced weakness.

See: 1342*

  • 1 reference to “rheumatoid arthritis”

An auto-immune disorder in which the immune system attacks tissues lining the body’s joints.

See: 2396*

  • 1 reference to “embryonal rhabdomyosarcoma”

A form of soft tissue cancer.

See: 3814*

Congenital Reproductive System Defects & Anomalies

39 total references

  • 1 reference to an unspecified “genital disorder male”

See: 51

  • 2 references to an unspecified “genital disorder female” or “congenital uterine anomaly”

See: 467, 762*

  • 1 reference to an unspecified “congenital genital malformation” (no sex provided)

See: 334

  • 18 references to “hypospadias”

Urethra opens on underside of penis, rather than at the tip.

See: 1165, 1167, 1168, 1624, 1996, 2005, 2084, 2097, 2098, 2104, 686*, 1227*, 2951*, 3059*, 3569*, 3767*, 3851*, 3864*

  • 6 references to “cryptorchism”

Or “cryptorchidism”; absence of one or both testes from scrotum.

See: 1624, 1996, 2005, 2084, 3767*, 3851*

  • 3 references to “chordee”

Abnormal curvature, either up or down, at meeting of penis head and shaft.

See: 3284*, 3569*, 3864*

  • 3 references to “hydrocele”

Sac filled with fluid that surrounds a testicle and causes scrotal swelling.

See: 1135, 1166, 1186

  • 1 reference to “penile torsion”

Penis appears “rotated” on its axis.

See: 3284*

  • 1 reference to “prepuce redundant”

Excessive foreskin.

See: 3284*

  • 3 references to “precocious puberty”

When the body enters puberty earlier than normal (before 8 for females; 9 for males). Precocious puberty is not necessarily caused by an abnormality in the reproductive system.

See: 931, 934, 937

Congenital Metabolic Disorders & Anomalies

24 total references

  • 21 references to “hypoglycemia neonatal”

Abnormally low blood sugar; long-term potential consequences range from developmental delay to seizure disorders.

See: 622, 743, 1133, 1133, 1171, 1173, 1184, 1185, 1315, 1316, 1358, 1965, 1808*, 1812*, 1812*, 1813*, 1893*, 2031*, 2217*, 2218*, 3341*

  • 2 references to “anemia neonatal”

Lack of sufficient red blood cells or hemoglobin, the protein that allows blood cells to carry oxygen.

See: 811*, 1181*

  • 1 reference to “hypometabolism”

Body’s biochemical reactions occur at slower pace than normal.

See: 775*

Genetic & Congenital Nervous System Disorders

84 total references

  • 1 reference to an unspecified “cytogenetic abnormality”

“Cytogenetic” refers to chromosomes.

See: 718*

  • 2 references to “Trisomy 21” or Down syndrome

See: 1711, 2102

  • 4 references to an unspecified “autism spectrum disorder” or simply “autism”

See: 2224, 1658*, 1658*, 2397*

  • 2 references to “meningomyelocele”

A form of spina bifida, in which the spinal canal and backbone fail to close before delivery.

See: 2117, 2184

  • 7 references to “tethered cord syndrome”

Attachments of tissue at base of spine limit spinal movement; often associated with forms of spina bifida.

See: 3284*, 3287*, 3288*, 3289*, 3291*, 3300*, 3616*

  • 1 reference to “hemiplegia”

Paralysis of one side of the body.

See: 3228*

  • 3 references to “epilepsy congenital”

See: 2017, 2209, 3862*

  • 2 references to an unspecified “nervous system disorder”

See: 928*, 1342*

  • 2 references to an “unspecified movement disorder” or “motor dysfunction”

See: 715*, 1658*

  • 4 references to “convulsion”

See: 1430*, 1430*, 2397*, 3117*

  • 9 references to “extrapyramidal disorder”

A category of movement disorders and related symptoms, including tremors and slurred speech.

See: 457, 460, 463, 471, 490, 504, 583, 638, 1695*

  • 5 references to “tardive dyskinesia”

Uncontrollable movements in certain muscle groups, predominantly facial, and an inability to remain motionless.

See: 490, 583, 643, 658, 703*

  • 1 reference to “myoclonus”

Brief, involuntary twitching of a muscle or muscle group. Myoclonus is a symptom, not a disease in itself.

See: 1321

  • 2 references to “dystonia”

Abnormality in muscle tone results in muscle spasms and abnormal posture; usually the result of a neurological disorder. One of many “extrapyramidal” symptoms.

See: 703*, 725*

  • 1 reference to “torticollis”

Head persistently turned to one side; often accompanied by painful muscle spasms.

See: 703*

  • 1 reference to “hyperreflexia”

Overresponsive reflexes; generally associated with a spinal cord injury or malformation.

See: 934*

  • 1 reference to “fetal hypokinesia”

Partial or complete loss of muscle movement, due to a disruption in the basal ganglia. A class of movement disorders that includes Parkinson’s disease.

See: 1617*

  • 1 reference to “neurosensory hypoacusis”

A form of hearing loss caused by degeneration or malformation of the middle ear, which normally translates vibrations in the air into neural impulses.

See: 2872*

  • 7 references to “cerebral cyst”

A fluid-filled sac in the brain.

See: 927, 601*, 738*, 3601*, 3641*, 3648*, 3889*

  • 1 reference to “periventricular leukomalacia”

Necrosis (premature cell death) or coagulation of brain’s white matter.

See: 3284*

  • 1 reference to “hypoxic-ischaemic encephalopathy”

Brain damage due to insufficient oxygen levels.

See: 811*

  • 3 references to “kernicterus”

Excessive levels of bilirubin leak from blood to brain tissue; occurs most commonly in children with jaundice.

See: 3601*, 3641*, 3648*

  • 4 references to “electroencephalogram abnormal”

An electroencephalogram, or “EEG,” registers electrical activity in the brain.

See: 463, 471, 583, 3117*

  • 1 reference to an unspecified “nerve injury”

See: 1621

  • 1 reference to an unspecified “facial nerve disorder”

See: 3649*

  • 2 references to “autonomic nervous system imbalance”

See: 457, 471

  • 1 reference to “trichotillomania”

Compulsive disorder in which sufferers pull out their own hair. This report pertained to a 121-day-old child.

See: 928*

  • 2 references to “emotional distress” or “disorder”

See: 3284*, 3569*

  • 1 reference to “anxiety”

See: 2397*

  • 1 reference to “depression”

See: 2397*

  • 1 reference to “social avoidant behavior”

See: 3284*

  • 2 references to “temperature regulation disorder” or “body temperature fluctuation”

See: 2826*, 2860*

  • 6 references to “hypothermia” or “hypothermia neonatal”

Abnormal, and generally dangerously low body temperature.

See: 622, 1808*, 1812*, 1812*, 1813*, 3814*

  • 1 reference to “hyperthermia”

Abnormally high body temperature.

See: 3088*

Congenital Skin & Nail Defects & Abnormalities

15 total references

  • 1 reference to an unspecified “skin malformation”

See: 2102

  • 1 reference to an unspecified “congenital nail disorder”

See: 2102

  • 1 reference to an unspecified “pigmentation disorder”

See: 1007*

  • 2 references to “aplasia cutis congenita”

Skin fails to form completely in a localized region.

See: 122, 1283*

  • 6 references to “alopecia”

Hair loss.

See: 122, 1208, 1208, 1211, 1211, 1211

  • 1 reference to “skin hypertrophy”

Raised scar tissue caused by the excessive production of collagen.

See: 51

  • 1 reference to “acne”

See: 122

  • 1 reference to “face oedema”

“Oedema” or “edema” is an abnormal build-up of fluid in body cavities or tissues.

See: 703*

  • 1 reference to “acrochordon”

Also known as a “skin tag”; a small benign tumor that generally forms at points where skin creases.

See: 1033*

Congenital Limb Disorders & Defects

20 total references

  • 1 reference to an unspecified “limb malformation”

See: 3889*

  • 4 references to an unspecified “foot deformity” or “malformation”

See: 2104, 972*, 972*, 1129*

  • 2 references to an unspecified “finger deformity”

See: 1085*, 1103*

  • 7 references to “talipes”

Or “club foot”; in most cases, the front portion of a baby’s foot is bent inwards and down.

See: 434, 445, 472, 1529*, 1536*, 3343*, 3345*

  • 3 references to “syndactyly”

Digits, either fingers or toes, are fused together.

See: 718*, 762*, 3114*

  • 1 reference to “polydactyly”

One or more extra digits, either fingers or toes.

See: 2103

  • 1 reference to “brachydactyly”

Abnormally shortened digits, relative to other long bones; generally caused by insufficient bone growth.

See: 934*

  • 1 reference to “limb reduction defect”

Limb, either arm or leg, fails to form properly; affected limb can either be reduced in size or absent.

See: 1246*

Congenital Eye Defects & Abnormalities

15 total references

  • 2 references to an unspecified “eye disorder”

See: 608*, 3649*

  • 5 references to “pupillary reflex impaired”

“Pupillary reflex” is the pupil’s ability to react to changing light levels.

See: 471, 583, 643, 658, 1695*

  • 2 references to “nystagmus”

Repetitive, uncontrollable eye movements.

See: 974*, 1342*

  • 1 reference to “strabismus”

Disorder in which the eyes are misaligned.

See: 987*

  • 1 reference to “amblyopia”

Or “lazy eye”; visual strength is reduced in one eye.

See: 972*

  • 1 reference to “photophobia”

Light sensitivity; bright light causes pain in eyes.

See: 3114*

  • 1 reference to “eye haemorrhage”

Broken blood vessel in eye.

See: 920*

  • 1 reference to “dacryostenosis congenital”

Duct that drains tears away from the eye is abnormally narrow.

See: 1621

  • 1 reference to “retinopathy of prematurity”

Affecting primarily premature babies, this condition involves abnormal blood vessel development in the eyes. May result in visual impairment or permanent blindness.

See: 1342*

Congenital Hepatobiliary Defects & Disorders

30 total references

Note: “hepatobiliary” refers to the physical system made up of the liver, gall bladder and bile ducts.

  • 1 reference to an unspecified “congenital hepatobiliary anomaly”

See: 1206

  • 20 references to “jaundice neonatal”

A yellow tint to the skin, eyes and excretions caused by increased levels of bilirubin, a substance found in bile.

See: 200, 622, 1133, 1186, 1519, 1666, 1874, 1895, 1964, 1089*, 1104*, 1808*, 1812*, 1812*, 1813*, 2826*, 2860*, 3476*, 3581*, 3814*

  • 6 references to “hyperbilirubinemia” or “blood bilirubin increased”

Elevated levels of bilirubin in the blood.

See: 899*, 1104*, 1808*, 1812*, 3213*, 3648*

  • 1 reference to “blood bilirubin unconjugated”

Often a causal factor resulting in jaundice.

See: 1317

  • 1 reference to “hepatic failure”

Liver failure.

See: 899*

  • 1 reference to “liver function test abnormal”

See: 725*

Congenital Thyroid Defects & Disorders

total references

  • 1 reference to “thyroiditis”

Inflammation of the thyroid, a gland in the neck that controls the rate at which energy is consumed in the body.

See: 821*

  • 1 reference to “thyroid function test abnormal”

See: 821*

  • 1 reference to “thyroid neoplasm”

“Neoplasm” refers to a tumor, either benign or malignant.

See: 821*

Other Adverse Fetal Outcomes & Fetal Environment Abnormalities

382 total references

  • 3 references to an unspecified “complication of pregnancy”

See: 353*, 383*, 504*

  • 32 references to “fetal death” or “stillbirth”

See: 273, 467, 644, 645, 1126, 1130, 1694, 1790, 1791, 2116, 2117, 495*, 610*, 626*, 718*, 718*, 753*, 762*, 865*, 986*, 1007*, 1094*, 1107*, 1158*, 1164*, 1171*, 1591*, 2090*, 2091*, 2390*, 3395*, 3889*

  • 16 references to “abortion spontaneous”

See: 2044, 2232, 678*, 903*, 980*, 1165*, 1181*, 1617*, 2316*, 2412*, 2600*, 2948*, 3082*, 3380*, 3657*, 3669*

  • 13 references to “abortion induced”

See: 330, 334, 334, 467, 518, 542, 673, 679, 684, 738*, 772*, 890*, 1584*

  • 5 references to “abortion missed”

A “missed abortion” occurs when a fetus is no longer viable, but the mother does not present any of the common symptoms of a miscarriage.

See: 66, 602*, 613*, 676*, 800*

  • 2 references to “abortion”

See: 892*, 1469*

  • 2 references to “SIDS” or “Sudden Infant Death Syndrome”

See: 1874, 1215*

  • 73 references to “premature baby”

See: 200, 364, 366, 463, 471, 490, 504, 583, 622, 658, 895, 902, 904, 1096, 1130, 1131, 1166, 1172, 1176, 1183, 1188, 1208, 1209, 1209, 1211, 1213, 1236, 1506, 1507, 1518, 1519, 1632, 1659, 1665, 1666, 1894, 1894, 1894, 1894, 718*, 934*, 986*, 987*, 1089*, 1104*, 1270*, 1271*, 1283*, 1292*, 1342*, 1808*, 1812*, 1812*, 1813*, 1896*, 2191*, 2895*, 2951*, 3033*, 3124*, 3213*, 3284*, 3492*, 3508*, 3511*, 3513*, 3543*, 3601*, 3641*, 3648*, 3773*, 3778*, 3814*

  • 16 references to “premature labor”

See: 201, 927, 1167, 1208, 1208, 1211, 1211, 1211, 1660, 1103*, 1282*, 2145*,  2859*, 3069*, 3081*, 3088*

  • 11 references to “premature delivery”

See: 1167, 1660, 2318*, 2319*, 2634*, 2849*, 2952*, 2987*, 3123*, 3256*, 3549*

  • 2 references to “abnormal labor”

See: 398*, 546*

  • 2 references to “arrested labor”

Lack of measurable progress in active labor that lasts two hours or longer.

See: 3002*, 3021*

  • 1 reference to “induced labor”

See: 658

  • 29 references to “cesarean section”

See: 364, 366, 743, 898, 904, 927, 1497, 1514, 1515, 775*, 777*, 811*, 941*, 1007*, 1282*, 1283*, 1292*, 1812*, 1828*, 1893*, 2145*, 2217*, 2317*, 2318*, 2849*, 2860*, 3123*, 3124*, 3778*

  • 4 references to “premature rupture of membranes”

Breakage of the amniotic sac more than an hour before the onset of labor.

See: 201, 941*, 1591*, 3256*

  • 1 reference to “artificial rupture of membranes”

Performed to accelerate labor.

See: 3117*

  • 1 reference to “amniorrhea”

Leaking amniotic fluid.

See: 2390*

  • 1 reference to “amniocentesis abnormal”

“Amniocentesis” is a prenatal medical procedure in which physicians extract a sample of amniotic fluid and test the substance for signs of genetic anomalies and infection. Amniocentesis is generally performed between the 16th and 20th weeks of pregnancy.

See: 811*

  • 2 references to “pre-eclampsia”

Pregnancy complication, generally beginning after the 20th week of pregnancy, characterized by elevated blood pressure and symptoms of organ damage, usually to the kidneys.

See: 3123*, 3549*

  • 1 reference to “premature separation of placenta”

Or “placental abruption”; placental lining separates from uterus before delivery.

See: 1660

  • 4 references to “oligohydramnios”

Deficient amount of amniotic fluid surrounding baby in womb.

See: 1211, 1519, 1666, 762*

  • 3 references to an unspecified “umbilical cord abnormality”

See: 1790, 865*, 1617*

  • 1 reference to “umbilical cord around neck”

See: 2952*

  • 3 references to an unspecified “placental disorder”

See: 273, 546*, 1260*

  • 3 references to “placental transfusion syndrome”

A disease affecting identical twin pregnancies; a shared placenta with abnormal blood vessels connects the circulatory systems and umbilical cords of the twins.

See: 1270*, 1271*, 1342*

  • 1 reference to “placental insufficiency”

Placenta is unable to deliver adequate amounts of oxygen and nutrients to developing baby.

See: 1790

  • 1 reference to “placenta praevia”

Placenta blocks the uterus, inhibiting delivery.

See: 2859*

  • 1 reference to “placenta praevia haemorrhage”

A case of placenta praevia in which bleeding occurs.

See: 2849*

  • 6 references to “haemorrhage”

See: 370, 546*, 980*, 1165*, 1171*, 1591*

  • 63 references to “fetal growth restriction” or “growth retardation”

Various definitions for “fetal growth restriction” have been proposed: fetal weight below the 10th percentile for gestational age is most common.

See: 273, 444, 448, 672, 673, 675, 679, 679, 684, 743, 895, 902, 904, 1131, 1133, 1133, 1135, 1164, 1171, 1172, 1173, 1176, 1184, 1185, 1188, 1236, 1311, 1315, 1316, 1317, 1358, 1502, 1503, 1506, 1507, 1508, 1510, 1511, 1513, 1515, 1518, 1519, 1665, 1666, 1840, 1874, 1965, 774*, 1281*, 1283*, 1284*, 1292*, 1554*, 1585*, 1893*, 2031*, 2217*, 2218*, 2318*, 2319*, 3059*, 3087*, 3213*

  • 18 references to “low birth weight baby”

See: 1208, 1209, 1209, 1211, 1213, 2895*, 1448, 1450, 1470, 3033*, 3114*, 3124*, 3213*, 1632, 3492*, 3543*, 3649*, 3773*

  • 4 references to “small for dates baby”

See: 463, 811*, 1695*, 3213*

  • 6 references to “weight decreased”

See: 583, 774*, 1342*, 2826*, 2860*, 3648*

  • 1 reference to “poor weight gain neonatal”

See: 3581*

  • 1 reference to “large for dates baby”

See: 1099

  • 1 reference to “body height below normal”

See: 934*

  • 17 references to an unspecified “feeding disorder neonatal”

See: 370, 1099, 1317, 1502, 1503, 1506, 1507, 1508, 1511, 1515, 1519, 1666, 1007*, 1896*, 2826*, 2860*, 3543*

  • 13 references to “drug withdrawal syndrome neonatal”

See: 457, 460, 463, 471, 504, 583, 643, 922*, 974*, 1695*, 2702*, 3010*, 3284*

  • 8 references to “Apgar score low”

“Apgar” (for Appearance, Pulse, Grimace, Activity, Respiration) is a test given to newborns directly after birth; a quick evaluation of a baby’s physical health.

See: 471, 583, 643, 702*, 702*, 811*, 1398*, 1695*

  • 5 references to “developmental delay”

According to the University of Michigan Health System, “child development refers to how a child becomes able to do more complex things as they get older.” Thus a “developmental delay” can be considered a delay in this process. Developmental delays can pertain to motor, language, social or cognitive skills.

See: 725*, 1342*, 3114*, 3284*, 3543*

  • 1 reference to “failure to thrive”

Insufficient weight gain of a newborn.

See: 3114*

  • 1 reference to “lipoatrophy”

A localized loss or absence of fat tissue.

See: 3649*

  • 1 reference to “systemic mastocytosis”

Levels of mast cells, a type of cell in the immune system, abnormally high in several organs.

See: 1791

  • 1 reference to “mastocytoma”

A type of tumor consisting of mast cells.

See: 3635*

  • 1 reference to “cystic lymphangioma”

Lesions or cysts in the lymphatic system.

See: 3889*

A Note On Our Numbers

The numbers listed above represent the total number of references a particular birth defect received in the adverse event reports Monheit Law was sent by the FDA. Many individual Adverse Event Reports list multiple separate birth defects. Further, where symptoms of a particular defect were listed alongside the abnormality, we counted only the defect itself.

Because one adverse event report may list multiple congenital anomalies, the number of specific conditions referenced in our list won’t correspond to the 475 total adverse fetal event reports provided by the FDA. Nor do the numbers presented here represent the true number of birth defect and adverse fetal events that may in fact be linked to prenatal exposure to Zofran.

Duplicate page numbers are not an error. Where numbers are repeated, a single page presented more than one adverse event report listing the same adverse fetal event.

Interpreting Adverse Event Reports

Adverse Event Reports utilize two levels of specificity in characterizing unfavorable health outcomes.

The broader level (referred to as “Outcome” in our FOIA reports) is a series of two-letter designations, like DE (for “Death”) or “LT” (for “Life-threatening”). These designations generally correspond to the severity of an adverse event or its repercussions, rather than the specific medical nature or diagnosis of the outcome being reported. Those more specific diagnoses are listed under the heading “Preferred Term.”

With that being said, one of the two-letter designations is “CA,” representing “Congenital Anomaly.” Unfortunately, the reporting of adverse events is far from rigorous. Many reports are incomplete and lack critical data. In our own experience, there were numerous AERs that clearly pertained to birth defects, or “congenital anomalies,” but had not been labeled “CA.” Many of these reports were instead classified as “OT,” for “Other.”

Here’s an example (from page 361):

OT AER

Under “Outcomes,” our high-level classification, we find “OT,” representing “Other.” But under “Preferred Term,” where specific diagnoses and symptoms are listed, we find “microcephaly.” Microcephaly is a congenital anomaly, a birth defect, but obviously this report hasn’t been labeled “CA.”

Under “Case Type,” we find “Expedited.” Only reports that have been submitted directly by pharmaceutical manufacturers are labeled “Expedited.” Reports submitted by health care professionals are labeled “Direct.”

Sometimes, it’s easy to tell which manufacturer submitted a report. It’s not visible in the image above, but each AER has another field labeled “Manufacturer Control #.” Reports Manufacturer Control Numbersubmitted by GlaxoSmithKline generally have a control number like the one to the right.

In referring to these data files, you may notice that we’ve changed the spelling of certain conditions. That’s because the FDA uses the Medical Dictionary for Regulatory Activities (MedDRA®), a standardized dictionary of medical terms. MedDRA uses many British spellings that aren’t as familiar to American readers, so we’ve altered them where appropriate.

Click on the buttons below to download the files we received in response to our FOIA request. Page numbers marked with an asterisk (*) refer to the first file, while unmarked page numbers can be found in the second.

Download PDF: Zofran Adverse Event FOIA Results : Branded & Generic Ondansetron

Download PDF: Zofran Adverse Event FOIA Results : Generic Ondansetron

Do Adverse Event Reports Present A Complete Picture?

No. In fact, many sources, including the US Food & Drug Administration, have stated that adverse event reporting in the United States is woefully inadequate.

According to QuarterWatch, a publication of the Institute for Safe Medication Practices that uses Adverse Event Report data to independently highlight potential safety issues, “both the FDA and QuarterWatch […] report[…] that the number of [adverse event] reports in children [are] too few for effective postmarket surveillance. For birth defects, reporting is even more limited, compounded by poor quality reporting.”

In other words, adverse event reporting in relation to birth defects is so infrequent, and of such poor quality, that the FDA’s Adverse Event Reporting System can’t even do what it was designed to: help regulators evaluate emerging safety risks from previously-approved pharmaceutical products.