Table 4.
Congenital anomalies
| Congenital anomaly | Reg. | EDC | First/Last Dose Date | Preg. Out. Date (Gestational Age) | Doses Received | Mother’s Age | Diagnosis Made by | Days of Drug Exposure Comment |
|---|---|---|---|---|---|---|---|---|
| Congenital heart anomaly, bilateral cleft lip, bilateral cleft palate, jaundice; exposed to study drugs EDC < LD | 9H | March 18, 2005 (by EDD − 266) | April 3, 2005/July 5, 2005 | December 6, 2005 (38 wk) | 80 | 29 | Physician report: | 94 d of drug exposure. No information about the type of heart anomaly. On the July 12, 2006 evaluation, it was reported that lip repair had been done, and that palate repair surgery was pending. |
| 1) Congenital heart anomaly NOS | ||||||||
| 2) Bilateral cleft lip | ||||||||
| 3) Bilateral cleft palate | ||||||||
| 4) Fetal jaundice NOS | ||||||||
| 5) Infant infectious | ||||||||
| Pyloric stenosis; exposed to study drugs EDC < LD | 9H | December 23, 2006 (by EDD − 266) | November 28, 2006/January 3, 2007 | August 6, 2007 (32 wk) | 26 | 26 | Symptoms of pyloric stenosis and abdominal ultrasound | 12 d of drug exposure. Baby boy developed frequent, nonbilious vomiting after discharge from the hospital; abdominal ultrasound: elongation of the pyloric channel up to 2.3 cm in length and circumferential thickening of the pyloric muscle measuring 2.7–4.1 mm; surgery: Fredet-Ramstedt pyloromyotomy. |
| Turner syndrome; not exposed to study drugs EDC > LD | 3HP | April 26, 2002 (by EDD − 266) | December 17, 2001/March 4, 2002 | July 25, 2002 (13 wk) | 12 | 35 | Ultrasound at Weeks 11 and 17: cystic hygroma and possible heart anomaly; amniocentesis karyotype confirmed Turner syndrome. | EDC 53 d after the last study dose. Confirmed diagnosis of Turner syndrome prompted elective medical abortion. Two pregnancies during the study. Diagnosis of hypochromic microcytic anemia on December 10, 2001. Received folic acid before conception. Past medical history of migraines treated with Amerge (naratriptan). |
| Down syndrome not exposed to study drugs EDC > LD | 3HP | October 15, 2007 (by LMP) | July 13, 2007/October 8, 2007 | February 22, 2008 (19 wk) | 12 | 36 | Positive quad test; no chromosomal analysis | EDC 7 d after the last study dose. On February 20, 2008, pregnant woman with morbid obesity was admitted to the hospital with vaginal bleeding and no fetal movement. Spontaneous abortion occurred 2 d later. Placenta was notable for extensive acute chorioamnionitis. Fetus had cystic hygroma at the neck with hydrops, and ears abnormally set. |
Definition of abbreviations: 3HP = 12-dose once-weekly regimen of isoniazid (900 mg) plus rifapentine (900 mg); 9H = 9-month daily isoniazid (300 mg); EDC = estimated date of conception; EDD = estimated date of delivery; LD = last study dose; LMP = last menstrual period; NOS = not otherwise specified; Preg. Out. = pregnancy outcome date; Reg. = regimen.
Rates: 1) cleft lip/palate and congenital anomaly, 1/940 live births (Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities [NCBDDD], U.S. Center for Disease Control and Prevention [CDC; https://www.cdc.gov/ncbddd/birthdefects/data.html]); 2) pyloric stenosis, 0.18–30.70 per 10,000 live births (U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research: evaluating the risk of drug exposure in human pregnancies, April 2005). 3) Turner syndrome, 1/2,500 live births (http://www.vivo.colostate.edu/hbooks/genetics/medgen/chromo_eg/turners.html); 4) Down syndrome, 1/691 live births (Division of Birth Defects and Developmental Disabilities, NCBDDD, CDC (https://www.cdc.gov/ncbddd/birthdefects/data.html). EDC < LD: EDC preceded the last study dose; EDC > LD: EDC followed the last study dose.