Supplementary Online Content Huybrechts KF, Hernández-Díaz S, Patorno E, et al. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry. Published online August 17, 2016. doi:10.1001/jamapsychiatry.2016.1520. etable 1. List of Antipsychotic Medications Included etable 2. Diagnostic Codes for Congenital Malformations etable 3. Women With Exposure to an Atypical AP During the First Trimester etable 4. Women With Exposure to a Typical AP During the First Trimester etable 5. Women With Exposure to Aripiprazole During the First Trimester etable 6. Women with Exposure to Olanzapine During the First Trimester etable 7. Women With Exposure to Quetiapine During the First Trimester etable 8. Women With Exposure to Risperidone During the First Trimester etable 9. Women With Exposure to Ziprasidone During the First Trimester etable 10. Relative Risks Comparing the Risk for Malformations Between AP-Exposed and Unexposed Women etable 11. Relative Risk for Malformations Between AP-Exposed and Unexposed Women: Sensitivity Analyses Using High-Dimensional PS and Restriction etable 12. Fully Adjusted Relative Risk for Malformations Between AP-Exposed and Unexposed Women: Sensitivity Analyses Varying Exposure and Outcome Definition etable 13. Fully Adjusted Relative Risk for Malformations Between AP-Exposed and Unexposed Women Stratified by Low, Medium, and High Dose etable 14. Relative Risk for Malformations Between Risperidone-Exposed and Unexposed Women Varying the Exposure Definition to Filling at Least 2 Prescriptions During The First Trimester etable 15. Relative Risk for Malformations Between Risperidone Continuers and Discontinuers Using Different Definitions for Discontinuers efigure 1. Study Diagram efigure 2. Study Flowchart eresults. Quantification of the Potential Impact of Missing Terminations This supplementary material has been provided by the authors to give readers additional information about their work.
etable 1. List of Antipsychotic Medications Included Atypical antipsychotics Typical antipsychotics Aripiprazole, Asenapine, Clozapine, Iloperidone, Lurasidone, Olanzapine, Olanzapine/fluoxetine, Paliperidone, Quetiapine, Risperidone, Ziprasidone Chlorpromazine, chlorprothixene, fluphenazine, haloperidol, loxapine, mesoridazine, molindone, perphenazine, perphenazine/amitriptyline, pimozide, promazine, thioridazine, thiothixene, trifluoperazine, triflupromazine
etable 2. Diagnostic Codes for Congenital Malformations Malformation Group ICD-9 Code 1. Central Nervous System 740.xx-742.xx 2. Eye Anomalies 743.xx (exclude if only 743.6x and 743.8x) 3. Ear Anomalies 744.xx (exclude if only 744.1x, 744.21, 744.29, and 744.4x-744.9x) 4. Cardiovascular Anomalies 745.xx-747.xx (exclude if only 745.5 AND preterm, 746.02 AND preterm, 746.4x, 746.6x, 746.99, 747.0x and preterm, 747.3 and preterm, 747.5x) 5. Other vascular (non-cardiac) 747.6x-747.9x (exclude if only 747.83) 6. Respiratory malformations 748.xx (do not count if only 748.1x) 7. Oral cleft 749.xx 8. Gastrointestinal 750.xx-751.xx (do not count if only 750.0x, 750.1x, 750.50, 751.0x) 9. Genital (male and female) 752.xx-753.xx (do not count if only 752.42, 752.52) (in addition, do not count 752.5x if preterm) 10. Urinary 753.xx (do not include if only 753.7x) 11. Musculoskeletal (no limbs, includes omphalocele ad gastroschisis) 754.xx and 756.xx (do not count if only 754.3x, 754.81, 754.82, 756.2x) 12. Limb defects 755.xx (exclude if only 755.65) 13. Other 757.xx; 759.xx (excl if only 757.2-757.6, 759.81-759.83)
etable 3. Women With Exposure to an Atypical AP During the First Trimester Characteristic Unadjusted Adjusted (1) Atypical APM (N=9,258) (3) Atypical APM (N=9,237) (N=1,289,826) Age, mean () 25.39 6.42 24.01 5.77 0.23 25.39 6.43 25.48 6.33-0.01 Year of delivery, N (%) 2000-2002 553 5.97 176,598 13.26-0.25 552 5.98 77,445 5.82 0.01 2003-2005 2,694 29.10 437,846 32.87-0.08 2,688 29.10 387,382 29.12 0.00 2006-2007 2,222 24.00 302,404 22.70 0.03 2,216 23.99 313,006 23.53 0.01 2008-2010 3,789 40.93 415,062 31.16 0.20 3,781 40.93 552,665 41.54-0.01 Race, N (%) White 5,856 63.25 532,864 40.01 0.48 5,842 63.25 901,761 67.78-0.10 Black 2,001 21.61 446,430 33.52-0.27 1,996 21.61 245,285 18.44 0.08 Hispanic 472 5.10 196,589 14.76-0.33 471 5.10 59,334 4.46 0.03 Other or unknown 929 10.03 156,027 11.71-0.05 928 10.05 124,119 9.33 0.02 Multiple gestation, N (%) 384 4.15 45,188 3.39 0.04 384 4.16 55,927 4.20 0.00 Antipsychotic indications, N (%) Bipolar disorder 3,165 34.19 9,548 0.72 0.98 3,144 34.04 397,813 29.90 0.09 Psychosis 537 5.80 1,655 0.12 0.34 521 5.64 62,138 4.67 0.04 Depression 2,985 32.24 62,931 4.72 0.76 2,972 32.17 480,077 36.08-0.08 Schizophrenia 761 8.22 873 0.07 0.42 740 8.01 67,722 5.09 0.12 Anxiety 2,373 25.63 41,813 3.14 0.68 2,362 25.57 374,207 28.13-0.06 ADHD 768 8.30 9,965 0.75 0.37 763 8.26 115,961 8.72-0.02 Other psychiatric disorders 964 10.41 14,930 1.12 0.41 946 10.24 130,588 9.81 0.01 Other mental and neurological conditions, N (%)
Characteristic Unadjusted Adjusted (1) Atypical APM (N=9,258) (3) Atypical APM (N=9,237) (N=1,289,826) Adjustment disorder 387 4.18 13,153 0.99 0.20 385 4.17 61,206 4.60-0.02 Delirium 85 0.92 768 0.06 0.12 84 0.91 11,671 0.88 0.00 Sleep disorders 396 4.28 8,135 0.61 0.24 394 4.27 63,327 4.76-0.02 Personality disorder 363 3.92 2,130 0.16 0.27 353 3.82 46,201 3.47 0.02 Alcohol abuse or dependence 393 4.24 6,669 0.50 0.25 385 4.17 53,274 4.00 0.01 Chronic fatigue syndrome 627 6.77 36,912 2.77 0.19 623 6.74 95,879 7.21-0.02 Drug abuse or dependence 916 9.89 16,256 1.22 0.39 908 9.83 127,411 9.58 0.01 Epilepsy or convulsions 311 3.36 8,830 0.66 0.20 303 3.28 45,052 3.39-0.01 Migraine/headache 1,433 15.48 92,100 6.91 0.27 1,425 15.43 221,315 16.63-0.03 Chronic maternal illness, N (%) Diabetes 311 3.36 23,780 1.79 0.10 307 3.32 46,169 3.47-0.01 Hypertension 392 4.23 25,028 1.88 0.14 391 4.23 58,987 4.43-0.01 Obesity 300 3.24 22,518 1.69 0.10 298 3.23 44,143 3.32-0.01 Renal disease 64 0.69 3,878 0.29 0.06 64 0.69 10,145 0.76-0.01 Smoking 882 9.53 39,418 2.96 0.27 877 9.49 130,899 9.84-0.01 Other psychotropic medications, N (%) Anticonvulsants 2,804 30.29 21,055 1.58 0.85 2,786 30.16 378,039 28.41 0.04 Antidepressants 6,629 71.60 107,131 8.04 1.71 6,608 71.54 1,070,319 80.44-0.21 Anxiolytics 398 4.30 4,305 0.32 0.27 394 4.27 60,021 4.51-0.01 Barbituates 288 3.11 12,992 0.98 0.15 287 3.11 46,987 3.53-0.02 Benzodiazepines 2,733 29.52 35,889 2.69 0.78 2,725 29.50 417,032 31.34-0.04 Other hypnotics 1,838 19.85 43,700 3.28 0.54 1,829 19.80 271,134 20.38-0.01 Stimulants for ADHD 937 10.12 7,789 0.58 0.43 935 10.12 138,814 10.43-0.01
Characteristic Unadjusted Adjusted (1) Atypical APM (N=9,258) (3) Atypical APM (N=9,237) (N=1,289,826) Other medications, N (%) Antidiabetics 151 1.63 8,973 0.67 0.09 149 1.61 21,942 1.65 0.00 Antihypertensives 723 7.81 28,278 2.12 0.26 722 7.82 108,126 8.13-0.01 Buphrenophine 119 1.29 1,084 0.08 0.15 119 1.29 17,359 1.30 0.00 Insulin 133 1.44 9,803 0.74 0.07 133 1.44 20,684 1.55-0.01 Methadone 30 0.32 697 0.05 0.06 30 0.32 4,632 0.35 0.00 Naloxone 118 1.27 1,240 0.09 0.14 118 1.28 17,182 1.29 0.00 Naltrexone 19 0.21 71 0.01 0.06 18 0.19 2,521 0.19 0.00 Opioids 3,616 39.06 254,845 19.13 0.45 3,609 39.07 558,292 41.96-0.06 Suspected teratogens, N (%) (2) 1,596 17.24 110,453 8.29 0.27 1,589 17.20 246,150 18.50-0.03 N of distinct prescriptions, excluding 4.75 3.98 1.63 2.31 0.96 4.74 3.98 5.04 3.95-0.08 APMs, mean () Patients hospitalized, N (%) 779 8.41 48,687 3.66 0.20 763 8.26 98,525 7.41 0.03 Proxies for severity Comorbidity Index, mean () 1.60 1.84 0.89 1.39 0.44 1.59 1.84 1.62 1.86-0.01 N of diagnoses, mean () 5.56 4.66 2.56 3.10 0.76 5.53 4.61 5.90 4.71-0.08 N of outpatient physician visits, 8.67 10.02 2.80 3.95 0.77 8.63 9.98 8.06 8.59 0.06 mean () N of hospitalizations, mean () 0.11 0.44 0.04 0.24 0.18 0.10 0.43 0.09 0.35 0.04 N of days hospitalized, mean () 0.48 2.25 0.13 0.93 0.20 0.47 2.20 0.40 2.17 0.03 N of ER visits, mean () 0.80 1.86 0.31 0.81 0.34 0.79 1.84 0.80 1.63-0.01 (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed.
(2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. (3) All antipsychotics were administered orally, except for 22 risperidone users who received injections. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 4. Women With Exposure to a Typical AP During the First Trimester Characteristic Unadjusted Adjusted (1) Typical APM (N=733) Typical APM (N=727) (N=1,297,638) Age, mean () 26.96 6.12 24.01 5.77 0.50 26.97 6.14 25.48 6.33-0.01 Year of delivery, N (%) 2000-2002 129 17.60 176,598 13.26 0.12 127 17.47 77,445 5.82 0.01 2003-2005 244 33.29 437,846 32.87 0.01 244 33.56 387,382 29.12 0.00 2006-2007 133 18.14 302,404 22.70-0.11 131 18.02 313,006 23.53 0.01 2008-2010 227 30.97 415,062 31.16 0.00 225 30.95 552,665 41.54-0.01 Race, N (%) White 356 48.57 532,864 40.01 0.17 354 48.69 901,761 67.78-0.10 Black 253 34.52 446,430 33.52 0.02 250 34.39 245,285 18.44 0.08 Hispanic 49 6.68 196,589 14.76-0.26 48 6.60 59,334 4.46 0.03 Other or unknown 75 10.23 156,027 11.71-0.05 75 10.32 124,119 9.33 0.02 Multiple gestation, N (%) 27 3.68 45,188 3.39 0.02 27 3.71 55,927 4.20 0.00 Antipsychotic indications, N (%) Bipolar disorder 201 27.42 9,548 0.72 0.83 195 26.82 397,813 29.90 0.09 Psychosis 95 12.96 1,655 0.12 0.54 90 12.38 62,138 4.67 0.04 Depression 192 26.19 62,931 4.72 0.62 189 26.00 480,077 36.08-0.08 Schizophrenia 160 21.83 873 0.07 0.74 154 21.18 67,722 5.09 0.12 Anxiety 134 18.28 41,813 3.14 0.50 131 18.02 374,207 28.13-0.06 ADHD 24 3.27 9,965 0.75 0.18 24 3.30 115,961 8.72-0.02 Other psychiatric disorders 73 9.96 14,930 1.12 0.39 69 9.49 130,588 9.81 0.01
Characteristic Unadjusted Adjusted (1) Typical APM (N=733) Typical APM (N=727) (N=1,297,638) Other mental and neurological conditions, N (%) Adjustment disorder 20 2.73 13,153 0.99 0.13 20 2.75 61,206 4.60-0.02 Delirium * * 768 0.06 0.16 * * 11,671 0.88 0.00 Sleep disorders 33 4.50 8,135 0.61 0.25 33 4.54 63,327 4.76-0.02 Personality disorder 37 5.05 2,130 0.16 0.31 36 4.95 46,201 3.47 0.02 Alcohol abuse or 38 5.18 6,669 0.50 0.28 34 4.68 53,274 4.00 0.01 dependence Chronic fatigue 67 9.14 36,912 2.77 0.27 66 9.08 95,879 7.21-0.02 syndrome Drug abuse or 59 8.05 16,256 1.22 0.33 57 7.84 127,411 9.58 0.01 dependence Epilepsy or convulsions 32 4.37 8,830 0.66 0.24 29 3.99 45,052 3.39-0.01 Migraine/headache 133 18.14 92,100 6.91 0.34 130 17.88 221,315 16.63-0.03 Chronic maternal illness, N (%) Diabetes 41 5.59 23,780 1.79 0.20 39 5.36 46,169 3.47-0.01 Hypertension 36 4.91 25,028 1.88 0.17 36 4.95 58,987 4.43-0.01 Obesity 30 4.09 22,518 1.69 0.14 28 3.85 44,143 3.32-0.01 Renal disease * * 3,878 0.29 0.02 * * 10,145 0.76-0.01 Smoking 68 9.28 39,418 2.96 0.27 65 8.94 130,899 9.84-0.01 Other psychotropic medications, N (%) Anticonvulsants 184 25.10 21,055 1.58 0.74 179 24.62 378,039 28.41 0.04
Characteristic Unadjusted Adjusted (1) Typical APM (N=733) Typical APM (N=727) (N=1,297,638) Antidepressants 389 53.07 107,131 8.04 1.12 383 52.68 1,070,319 80.44-0.21 Anxiolytics 25 3.41 4,305 0.32 0.23 24 3.30 60,021 4.51-0.01 Barbituates 33 4.50 12,992 0.98 0.22 33 4.54 46,987 3.53-0.02 Benzodiazepines 173 23.60 35,889 2.69 0.65 169 23.25 417,032 31.34-0.04 Other hypnotics 175 23.87 43,700 3.28 0.63 172 23.66 271,134 20.38-0.01 Stimulants for ADHD 29 3.96 7,789 0.58 0.23 154 21.18 138,814 10.43-0.01 Other medications, N (%) Antidiabetics 22 3.00 8,973 0.67 0.17 21 2.89 21,942 1.65 0.00 Antihypertensives 52 7.09 28,278 2.12 0.24 52 7.15 108,126 8.13-0.01 Buphrenophine * * 1,084 0.08 0.07 * * 17,359 1.30 0.00 Insulin 16 2.18 9,803 0.74 0.12 16 2.20 20,684 1.55-0.01 Methadone * * 697 0.05 0.07 * * 4,632 0.35 0.00 Naloxone * * 1,240 0.09 0.06 * * 17,182 1.29 0.00 Naltrexone * * 71 0.01-0.01 * * 2,521 0.19 0.00 Opioids 255 34.79 254,845 19.13 0.36 254 34.94 558,292 41.96-0.06 Suspected teratogens, N 99 13.51 110,453 8.29 0.17 98 13.48 246,150 18.50-0.03 (%) (2) N of distinct prescriptions, 4.19 3.92 1.63 2.31 0.79 4.14 3.96 5.04 3.95-0.08 excluding APMs, mean () Patients hospitalized, N 74 10.10 48,687 3.66 0.26 68 9.35 98,525 7.41 0.03 (%) Proxies for severity Comorbidity Index, mean 1.59 1.91 0.89 1.39 0.42 1.57 1.92 1.62 1.86-0.01
Characteristic Unadjusted Adjusted (1) () N of diagnoses, mean () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, mean () N of ER visits, mean Typical APM (N=733) Typical APM (N=727) (N=1,297,638) 5.48 5.22 2.56 3.10 0.68 5.37 5.10 5.90 4.71-0.08 8.87 11.31 2.80 3.95 0.72 8.53 10.79 8.06 8.59 0.06 0.14 0.46 0.04 0.24 0.25 0.12 0.41 0.09 0.35 0.04 0.62 2.53 0.13 0.93 0.25 0.56 2.43 0.40 2.17 0.03 0.98 2.98 0.31 0.81 0.31 0.96 2.97 0.80 1.63-0.01 () *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 5. Women With Exposure to Aripiprazole During the First Trimester Characteristic Unadjusted Adjusted (1) Aripiprazole (N=1,756) Aripiprazole (N=1,752) (N=957,012) Age, mean () 24.20 6.30 24.01 5.77 0.03 24.17 6.31 24.41 6.22-0.03 Year of delivery, N (%) 2000-2002 0 0.00 176,598 13.26-0.55 0 0.00 102 0.01-0.01 2003-2005 230 13.10 437,846 32.87-0.48 230 13.13 163,790 12.40 0.02 2006-2007 398 22.67 302,404 22.70 0.00 396 22.60 292,436 22.14 0.01 2008-2010 1,128 64.24 415,062 31.16 0.70 1,126 64.27 864,683 65.46-0.02 Race, N (%) White 1,101 62.70 532,864 40.01 0.47 1,099 62.73 886,892 67.14-0.09 Black 391 22.27 446,430 33.52-0.25 389 22.20 259,403 19.64 0.06 Hispanic 85 4.84 196,589 14.76-0.34 85 4.85 52,215 3.95 0.04 Other or unknown 179 10.19 156,027 11.71-0.05 179 10.22 122,500 9.27 0.03 Multiple gestation, N (%) 79 4.50 45,188 3.39 0.06 79 4.51 60,895 4.61 0.00 Antipsychotic indications, N (%) Bipolar disorder 744 42.37 9,548 0.72 1.17 740 42.24 516,932 39.13 0.06 Psychosis 91 5.18 1,655 0.12 0.32 88 5.02 51,732 3.92 0.05 Depression 520 29.61 62,931 4.72 0.70 518 29.57 433,343 32.80-0.07 Schizophrenia 137 7.80 873 0.07 0.41 133 7.59 67,832 5.13 0.10 Anxiety 429 24.43 41,813 3.14 0.65 428 24.43 356,928 27.02-0.06 ADHD 196 11.16 9,965 0.75 0.45 195 11.13 146,498 11.09 0.00 Other psychiatric disorders 200 11.39 14,930 1.12 0.43 196 11.19 138,788 10.51 0.02
Characteristic Unadjusted Adjusted (1) Aripiprazole (N=1,756) Aripiprazole (N=1,752) (N=957,012) Other mental and neurological conditions, N (%) Adjustment disorder 79 4.50 13,153 0.99 0.22 79 4.51 66,169 5.01-0.02 Delirium 15 0.85 768 0.06 0.12 15 0.86 10,629 0.80 0.01 Sleep disorders 57 3.25 8,135 0.61 0.19 57 3.25 47,032 3.56-0.02 Personality disorder 81 4.61 2,130 0.16 0.29 79 4.51 50,335 3.81 0.04 Alcohol abuse or 64 3.64 6,669 0.50 0.22 62 3.54 43,204 3.27 0.01 dependence Chronic fatigue syndrome 116 6.61 36,912 2.77 0.18 115 6.56 95,604 7.24-0.03 Drug abuse or dependence 114 6.49 16,256 1.22 0.28 113 6.45 86,117 6.52 0.00 Epilepsy or convulsions 49 2.79 8,830 0.66 0.16 48 2.74 35,499 2.69 0.00 Migraine/headache 250 14.24 92,100 6.91 0.24 248 14.16 197,617 14.96-0.02 Chronic maternal illness, N (%) Diabetes 65 3.70 23,780 1.79 0.12 64 3.65 45,094 3.41 0.01 Hypertension 72 4.10 25,028 1.88 0.13 71 4.05 56,311 4.26-0.01 Obesity 85 4.84 22,518 1.69 0.18 83 4.74 60,763 4.60 0.01 Renal disease 12 0.68 3,878 0.29 0.06 12 0.68 9,200 0.70 0.00 Smoking 187 10.65 39,418 2.96 0.31 185 10.56 142,060 10.75-0.01 Other psychotropic medications, N (%) Anticonvulsants 534 30.41 21,055 1.58 0.86 530 30.25 388,381 29.40 0.02 Antidepressants 1,195 68.05 107,131 8.04 1.57 1,191 67.98 998,281 75.57-0.17
Characteristic Unadjusted Adjusted (1) Aripiprazole (N=1,756) Aripiprazole (N=1,752) (N=957,012) Anxiolytics 74 4.21 4,305 0.32 0.26 74 4.22 57,723 4.37-0.01 Barbituates 41 2.33 12,992 0.98 0.11 41 2.34 32,964 2.50-0.01 Benzodiazepines 484 27.56 35,889 2.69 0.74 483 27.57 390,662 29.57-0.04 Other hypnotics 387 22.04 43,700 3.28 0.59 387 22.09 290,535 21.99 0.00 Stimulants for ADHD 243 13.84 7,789 0.58 0.53 242 13.81 181,349 13.73 0.00 Other medications, N (%) Antidiabetics 30 1.71 8,973 0.67 0.10 30 1.71 21,281 1.61 0.01 Antihypertensives 148 8.43 28,278 2.12 0.28 147 8.39 116,996 8.86-0.02 Buphrenophine 21 1.20 1,084 0.08 0.14 21 1.20 16,876 1.28-0.01 Insulin 27 1.54 9,803 0.74 0.08 27 1.54 19,491 1.48 0.01 Methadone * * 697 0.05 0.06 * * 4,099 0.31 0.00 Naloxone 20 1.14 1,240 0.09 0.13 20 1.14 16,116 1.22-0.01 Naltrexone * * 71 0.01 0.04 * * 1,863 0.14-0.01 Opioids 652 37.13 254,845 19.13 0.41 651 37.16 525,711 39.80-0.05 Suspected teratogens, N 280 15.95 110,453 8.29 0.24 278 15.87 221,414 16.76-0.02 (%) (2) N of distinct prescriptions, 4.69 3.88 1.63 2.31 0.95 4.69 3.90 4.96 3.84-0.07 excluding APMs, mean () Patients hospitalized, N (%) 148 8.43 48,687 3.66 0.20 144 8.22 93,868 7.11 0.04 Proxies for severity Comorbidity Index, mean 1.41 1.73 0.89 1.39 0.33 1.40 1.73 1.47 1.81-0.03 () N of diagnoses, mean 5.84 4.67 2.56 3.10 0.83 5.84 4.70 6.16 4.67-0.07
Characteristic Unadjusted Adjusted (1) () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, Aripiprazole (N=1,756) Aripiprazole (N=1,752) (N=957,012) 9.39 10.80 2.80 3.95 0.81 9.33 10.75 8.57 8.75 0.08 0.10 0.37 0.04 0.24 0.19 0.10 0.37 0.08 0.32 0.05 0.48 2.10 0.13 0.93 0.21 0.46 2.06 0.39 2.09 0.04 mean () N of ER visits, mean () 0.75 1.43 0.31 0.81 0.38 0.75 1.44 0.78 1.53-0.02 *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 6. Women With Exposure to Olanzapine During the First Trimester Characteristic Unadjusted Adjusted (1) Olanzapine (N=1,394) Olanzapine (N=1,392) (N=1,231,441) Age, mean () 26.63 6.39 24.01 5.77 0.43 26.55 6.36 26.69 6.34-0.01 Year of delivery, N (%) 2000-2002 248 17.79 176,598 13.26 0.13 247 17.74 227,355 17.12 0.02 2003-2005 687 49.28 437,846 32.87 0.34 686 49.28 674,260 50.77-0.03 2006-2007 228 16.36 302,404 22.70-0.16 228 16.38 211,211 15.90 0.01 2008-2010 231 16.57 415,062 31.16-0.35 231 16.59 215,174 16.20 0.01 Race, N (%) White 781 56.03 532,864 40.01 0.32 780 56.03 799,228 60.18-0.08 Black 332 23.82 446,430 33.52-0.22 332 23.85 275,473 20.74 0.07 Hispanic 102 7.32 196,589 14.76-0.24 101 7.26 85,124 6.41 0.03 Other or unknown 179 12.84 156,027 11.71 0.03 179 12.86 168,175 12.66 0.01 Multiple gestation, N (%) 50 3.59 45,188 3.39 0.01 50 3.59 46,374 3.49 0.01 Antipsychotic indications, N (%) Bipolar disorder 429 30.77 9,548 0.72 0.91 427 30.68 379,029 28.54 0.05 Psychosis 103 7.39 1,655 0.12 0.39 101 7.26 70,127 5.28 0.08 Depression 442 31.71 62,931 4.72 0.75 442 31.75 466,472 35.13-0.07 Schizophrenia 178 12.77 873 0.07 0.54 176 12.64 111,735 8.41 0.14 Anxiety 317 22.74 41,813 3.14 0.61 317 22.77 328,057 24.70-0.05 ADHD 73 5.24 9,965 0.75 0.27 73 5.24 69,607 5.24 0.00 Other psychiatric disorders 127 9.11 14,930 1.12 0.37 126 9.05 110,690 8.34 0.03
Characteristic Unadjusted Adjusted (1) Olanzapine (N=1,394) Olanzapine (N=1,392) (N=1,231,441) Other mental and neurological conditions, N (%) Adjustment disorder 70 5.02 13,153 0.99 0.24 69 4.96 72,326 5.45-0.02 Delirium 11 0.79 768 0.06 0.11 11 0.79 8,666 0.65 0.02 Sleep disorders 62 4.45 8,135 0.61 0.25 62 4.45 65,688 4.95-0.02 Personality disorder 62 4.45 2,130 0.16 0.29 61 4.38 52,247 3.93 0.02 Alcohol abuse or 68 4.88 6,669 0.50 0.27 67 4.81 60,890 4.59 0.01 dependence Chronic fatigue 102 7.32 36,912 2.77 0.21 102 7.33 106,103 7.99-0.02 syndrome Drug abuse or 153 10.98 16,256 1.22 0.42 153 10.99 141,174 10.63 0.01 dependence Epilepsy or convulsions 49 3.52 8,830 0.66 0.20 49 3.52 45,352 3.42 0.01 Migraine/headache 225 16.14 92,100 6.91 0.29 224 16.09 230,214 17.34-0.03 Chronic maternal illness, N (%) Diabetes 38 2.73 23,780 1.79 0.06 38 2.73 39,008 2.94-0.01 Hypertension 50 3.59 25,028 1.88 0.10 50 3.59 48,967 3.69-0.01 Obesity 35 2.51 22,518 1.69 0.06 35 2.51 35,464 2.67-0.01 Renal disease * * 3,878 0.29 0.02 * * 6,639 0.50-0.01 Smoking 122 8.75 39,418 2.96 0.25 122 8.76 118,222 8.90 0.00 Other psychotropic medications, N (%) Anticonvulsants 351 25.18 21,055 1.58 0.74 349 25.07 325,632 24.52 0.01
Characteristic Unadjusted Adjusted (1) Olanzapine (N=1,394) Olanzapine (N=1,392) (N=1,231,441) Antidepressants 959 68.79 107,131 8.04 1.60 957 68.75 1,040,593 78.36-0.22 Anxiolytics 48 3.44 4,305 0.32 0.23 47 3.38 50,872 3.83-0.02 Barbituates 39 2.80 12,992 0.98 0.13 39 2.80 40,192 3.03-0.01 Benzodiazepines 410 29.41 35,889 2.69 0.78 409 29.38 418,228 31.49-0.05 Other hypnotics 252 18.08 43,700 3.28 0.49 252 18.10 253,821 19.11-0.03 Stimulants for ADHD 85 6.10 7,789 0.58 0.31 85 6.11 83,659 6.30-0.01 Other medications, N (%) Antidiabetics 15 1.08 8,973 0.67 0.04 15 1.08 15,402 1.16-0.01 Antihypertensives 99 7.10 28,278 2.12 0.24 99 7.11 99,781 7.51-0.02 Buphrenophine * * 1,084 0.08 0.07 * * 6,187 0.47-0.01 Insulin 14 1.00 9,803 0.74 0.03 14 1.01 15,680 1.18-0.02 Methadone * * 697 0.05 0.06 * * 3,890 0.29 0.00 Naloxone * * 1,240 0.09 0.75 * * 7,181 0.54-0.01 Naltrexone * * 71 0.01 0.07 * * 2,675 0.20 0.02 Opioids 502 36.01 254,845 19.13 0.38 501 35.99 516,573 38.90-0.06 Suspected teratogens, N 248 17.79 110,453 8.29 0.28 247 17.74 256,080 19.28-0.04 (%) (2) N of distinct prescriptions, 4.55 3.97 1.63 2.31 0.90 4.54 3.98 4.87 3.97-0.08 excluding APMs, mean () Patients hospitalized, N 125 8.97 48,687 3.66 0.22 123 8.84 106,499 8.02 0.03 (%) Proxies for severity Comorbidity Index, mean 1.63 1.89 0.89 1.39 0.45 1.62 1.90 1.65 1.86-0.01
Characteristic Unadjusted Adjusted (1) () N of diagnoses, mean () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, mean () N of ER visits, mean Olanzapine (N=1,394) Olanzapine (N=1,392) (N=1,231,441) 5.06 4.54 2.56 3.10 0.64 5.07 4.56 5.32 4.61-0.06 8.11 10.15 2.80 3.95 0.69 8.17 10.27 7.62 8.44 0.05 0.11 0.38 0.04 0.24 0.21 0.11 0.38 0.10 0.37 0.03 0.49 2.15 0.13 0.93 0.22 0.49 2.16 0.45 2.39 0.02 0.67 1.57 0.31 0.81 0.29 0.68 1.59 0.66 1.51 0.00 () *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 7. Women With Exposure to Quetiapine During the First Trimester Characteristic Unadjusted Adjusted (1) Quetiapine (N=4,221) Quetiapine (N=4,213) (N=1,161,955) Age, mean () 25.86 6.34 24.01 5.77 0.31 25.84 6.34 25.90 6.27-0.01 Year of delivery, N (%) 2000-2002 148 3.51 176,598 13.26-0.36 148 3.51 44,266 3.34 0.01 2003-2005 1,148 27.20 437,846 32.87-0.12 1,146 27.20 359,490 27.10 0.00 2006-2007 1,147 27.17 302,404 22.70 0.10 1,145 27.18 354,618 26.73 0.01 2008-2010 1,778 42.12 415,062 31.16 0.23 1,774 42.11 568,352 42.84-0.01 Race, N (%) White 2,880 68.23 532,864 40.01 0.59 2,874 68.22 955,126 71.99-0.08 Black 765 18.12 446,430 33.52-0.36 764 18.13 206,300 15.55 0.07 Hispanic 171 4.05 196,589 14.76-0.37 171 4.06 47,221 3.56 0.03 Other or unknown 405 9.59 156,027 11.71-0.07 404 9.59 118,079 8.90 0.02 Multiple gestation, N (%) 181 4.29 45,188 3.39 0.05 181 4.30 57,826 4.36 0.00 Antipsychotic indications, N (%) Bipolar disorder 1,420 33.64 9,548 0.72 0.97 1,412 33.52 375,312 28.29 0.11 Psychosis 188 4.45 1,655 0.12 0.29 183 4.34 44,516 3.36 0.05 Depression 1,421 33.67 62,931 4.72 0.79 1,415 33.59 487,901 36.77-0.07 Schizophrenia 240 5.69 873 0.07 0.34 232 5.51 48,330 3.64 0.09 Anxiety 1,188 28.14 41,813 3.14 0.73 1,182 28.06 392,141 29.56-0.03 ADHD 327 7.75 9,965 0.75 0.35 326 7.74 103,242 7.78 0.00 Other psychiatric disorders 402 9.52 14,930 1.12 0.38 395 9.38 115,773 8.73 0.02
Characteristic Unadjusted Adjusted (1) Quetiapine (N=4,221) Quetiapine (N=4,213) (N=1,161,955) Other mental and neurological conditions, N (%) Adjustment disorder 157 3.72 13,153 0.99 0.18 157 3.73 52,966 3.99-0.01 Delirium 45 1.07 768 0.06 0.14 45 1.07 12,758 0.96 0.01 Sleep disorders 206 4.88 8,135 0.61 0.26 205 4.87 70,391 5.31-0.02 Personality disorder 153 3.62 2,130 0.16 0.26 151 3.58 40,108 3.02 0.03 Alcohol abuse or 209 4.95 6,669 0.50 0.28 207 4.91 58,816 4.43 0.02 dependence Chronic fatigue 280 6.63 36,912 2.77 0.18 279 6.62 93,042 7.01-0.02 syndrome Drug abuse or 513 12.15 16,256 1.22 0.45 509 12.08 148,395 11.19 0.03 dependence Epilepsy or convulsions 145 3.44 8,830 0.66 0.20 141 3.35 43,984 3.32 0.00 Migraine/headache 676 16.02 92,100 6.91 0.29 673 15.97 223,591 16.85-0.02 Chronic maternal illness, N (%) Diabetes 139 3.29 23,780 1.79 0.10 137 3.25 45,995 3.47-0.01 Hypertension 199 4.71 25,028 1.88 0.16 199 4.72 62,288 4.69 0.00 Obesity 116 2.75 22,518 1.69 0.07 116 2.75 37,528 2.83 0.00 Renal disease 39 0.92 3,878 0.29 0.08 39 0.93 12,357 0.93 0.00 Smoking 440 10.42 39,418 2.96 0.30 438 10.40 138,823 10.46 0.00 Other psychotropic medications, N (%) Anticonvulsants 1,347 31.91 21,055 1.58 0.89 1,340 31.81 387,398 29.20 0.06
Characteristic Unadjusted Adjusted (1) Quetiapine (N=4,221) Quetiapine (N=4,213) (N=1,161,955) Antidepressants 3,137 74.32 107,131 8.04 1.82 3,129 74.27 1,094,554 82.50-0.20 Anxiolytics 208 4.93 4,305 0.32 0.29 206 4.89 65,979 4.97 0.00 Barbituates 162 3.84 12,992 0.98 0.19 162 3.85 54,640 4.12-0.01 Benzodiazepines 1,386 32.84 35,889 2.69 0.86 1,383 32.83 446,753 33.67-0.02 Other hypnotics 890 21.09 43,700 3.28 0.57 884 20.98 278,353 20.98 0.00 Stimulants for ADHD 409 9.69 7,789 0.58 0.42 409 9.71 127,098 9.58 0.00 Other medications, N (%) Antidiabetics 72 1.71 8,973 0.67 0.10 70 1.66 23,414 1.76-0.01 Antihypertensives 340 8.05 28,278 2.12 0.27 340 8.07 108,656 8.19 0.00 Buphrenophine 87 2.06 12,206 0.92 0.09 87 2.07 25,530 1.92 0.01 Insulin 63 1.49 9,803 0.74 0.07 63 1.50 22,117 1.67-0.01 Methadone 19 0.45 3,744 0.28 0.03 19 0.45 6,012 0.45 0.00 Naloxone 85 2.01 1,240 0.09 0.19 85 2.02 24,963 1.88 0.01 Naltrexone * * 71 0.01 0.07 * * 2,573 0.19 0.01 Opioids 1,836 43.50 254,845 19.13 0.54 1,834 43.53 604,319 45.55-0.04 Suspected teratogens, N 757 17.93 110,453 8.29 0.29 756 17.94 248,902 18.76-0.02 (%) (2) N of distinct prescriptions, 5.10 6.10 7.10 8.10 9.10 5.09 4.12 5.30 3.98-0.05 excluding APMs, mean () Patients hospitalized, N 365 8.65 48,687 3.66 0.21 361 8.57 100,033 7.54 0.04 (%) Proxies for severity Comorbidity Index, mean 1.74 1.89 0.89 1.39 0.52 1.74 1.88 1.74 1.89 0.00
Characteristic Unadjusted Adjusted (1) () N of diagnoses, mean () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, mean () N of ER visits, mean Quetiapine (N=4,221) Quetiapine (N=4,213) (N=1,161,955) 5.80 4.75 2.56 3.10 0.81 5.78 4.71 6.07 4.73-0.06 8.90 10.08 2.80 3.95 0.80 8.88 10.03 8.15 8.59 0.08 0.11 0.43 0.04 0.24 0.19 0.11 0.43 0.09 0.35 0.05 0.50 2.33 0.13 0.93 0.20 0.49 2.29 0.40 2.07 0.04 0.87 1.81 0.31 0.81 0.40 0.86 1.76 0.84 1.66 0.01 () *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 8. Women With Exposure to Risperidone During the First Trimester Characteristic Unadjusted Adjusted (1) Risperidone (N=1,566) Risperidone (N=1,565) (N=1,290,485) Age, mean () 24.81 6.73 24.01 5.77 0.13 24.84 6.76 25.03 6.55-0.03 Year of delivery, N (%) 2000-2002 159 10.15 176,598 13.26-0.10 159 10.16 131,259 9.86 0.01 2003-2005 595 37.99 437,846 32.87 0.11 595 38.02 510,989 38.40-0.01 2006-2007 355 22.67 302,404 22.70 0.00 354 22.62 296,499 22.28 0.01 2008-2010 457 29.18 415,062 31.16-0.04 457 29.20 391,828 29.45-0.01 Race, N (%) White 852 54.41 532,864 40.01 0.29 852 54.44 795,857 59.81-0.11 Black 441 28.16 446,430 33.52-0.12 440 28.12 322,918 24.27 0.09 Hispanic 105 6.70 196,589 14.76-0.26 105 6.71 80,057 6.02 0.03 Other or unknown 168 10.73 156,027 11.71-0.03 168 10.73 131,742 9.90 0.03 Multiple gestation, N (%) 66 4.21 45,188 3.39 0.04 66 4.22 59,417 4.47-0.01 Antipsychotic indications, N (%) Bipolar disorder 445 28.42 9,548 0.72 0.85 444 28.37 336,729 25.31 0.07 Psychosis 140 8.94 1,655 0.12 0.43 139 8.88 80,244 6.03 0.11 Depression 519 33.14 62,931 4.72 0.78 518 33.10 488,280 36.70-0.08 Schizophrenia 175 11.17 873 0.07 0.50 174 11.12 88,359 6.64 0.16 Anxiety 363 23.18 41,813 3.14 0.62 362 23.13 342,072 25.71-0.06 ADHD 149 9.51 9,965 0.75 0.41 149 9.52 122,655 9.22 0.01 Other psychiatric disorders 196 12.52 14,930 1.12 0.46 195 12.46 152,826 11.49 0.03
Characteristic Unadjusted Adjusted (1) Risperidone (N=1,566) Risperidone (N=1,565) (N=1,290,485) Other mental and neurological conditions, N (%) Adjustment disorder 77 4.92 13,153 0.99 0.23 76 4.86 69,712 5.24-0.02 Delirium 15 0.96 768 0.06 0.13 15 0.96 10,198 0.77 0.02 Sleep disorders 49 3.13 8,135 0.61 0.19 49 3.13 44,735 3.36-0.01 Personality disorder 61 3.90 2,130 0.16 0.27 60 3.83 41,466 3.12 0.04 Alcohol abuse or 52 3.32 6,669 0.50 0.21 52 3.32 43,775 3.29 0.00 dependence Chronic fatigue 99 6.32 36,912 2.77 0.17 99 6.33 89,717 6.74-0.02 syndrome Drug abuse or 139 8.88 16,256 1.22 0.36 138 8.82 115,103 8.65 0.01 dependence Epilepsy or convulsions 52 3.32 6,669 0.50 0.21 52 3.32 41,852 3.15 0.01 Migraine/headache 233 14.88 92,100 6.91 0.26 233 14.89 219,137 16.47-0.04 Chronic maternal illness, N (%) Diabetes 55 3.51 23,780 1.79 0.11 55 3.51 47,190 3.55 0.00 Hypertension 57 3.64 25,028 1.88 0.11 57 3.64 51,896 3.90-0.01 Obesity 48 3.07 22,518 1.69 0.09 48 3.07 40,009 3.01 0.00 Renal disease * * 1,466 0.11 0.08 * * 8,831 0.66-0.01 Smoking 114 7.28 39,418 2.96 0.20 114 7.28 102,985 7.74-0.02 Other psychotropic medications, N (%) Anticonvulsants 476 30.40 21,055 1.58 0.85 476 30.42 381,289 28.66 0.04
Characteristic Unadjusted Adjusted (1) Risperidone (N=1,566) Risperidone (N=1,565) (N=1,290,485) Antidepressants 1,151 73.50 107,131 8.04 1.79 1,150 73.48 1,124,889 84.54-0.27 Anxiolytics 56 3.58 4,305 0.32 0.24 56 3.58 51,176 3.85-0.01 Barbituates 38 2.43 12,992 0.98 0.11 38 2.43 37,633 2.83-0.03 Benzodiazepines 378 24.14 35,889 2.69 0.66 * * 4,690 0.35-0.01 Other hypnotics 263 16.79 43,700 3.28 0.46 262 16.74 232,497 17.47-0.02 Stimulants for ADHD 173 11.05 7,789 0.58 0.46 173 11.05 144,388 10.85 0.01 Other medications, N (%) Antidiabetics 29 1.85 8,973 0.67 0.11 29 1.85 25,557 1.92 0.00 Antihypertensives 116 7.41 28,278 2.12 0.25 116 7.41 102,425 7.70-0.01 Buphrenophine * * 9,127 0.69-0.05 * * 4,690 0.35-0.01 Insulin 24 1.53 6,119 0.46 0.11 24 1.53 20,893 1.57 0.00 Methadone * * 240 0.02 0.04 * * 2,161 0.16-0.01 Naloxone * * 1,240 0.09 0.06 * * 5,674 0.43-0.01 Naltrexone * * 395 0.03 0.05 * * 2,090 0.16 0.01 Opioids 497 31.74 254,845 19.13 0.29 497 31.76 459,496 34.53-0.06 Suspected teratogens, N 264 16.86 110,453 8.29 0.26 264 16.87 237,615 17.86-0.03 (%) (2) N of distinct prescriptions, 4.30 3.87 1.63 2.31 0.84 4.27 3.85 4.68 3.87-0.10 excluding APMs, mean () Patients hospitalized, N 123 7.85 48,687 3.66 0.18 123 7.86 90,784 6.82 0.04 (%) Proxies for severity Comorbidity Index, mean 1.53 1.88 0.89 1.39 0.39 1.54 1.87 1.53 1.82 0.00
Characteristic Unadjusted Adjusted (1) () N of diagnoses, mean () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, mean () N of ER visits, mean Risperidone (N=1,566) Risperidone (N=1,565) (N=1,290,485) 5.17 4.50 2.56 3.10 0.68 5.13 4.49 5.51 4.53-0.07 8.14 9.51 2.80 3.95 0.73 8.06 9.43 7.98 8.84 0.02 0.11 0.57 0.04 0.24 0.16 0.11 0.57 0.09 0.36 0.06 0.50 2.60 0.13 0.93 0.19 0.51 2.64 0.39 2.24 0.04 0.71 1.55 0.31 0.81 0.32 0.70 1.53 0.72 1.57 0.00 () *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 9. Women With Exposure to Ziprasidone During the First Trimester Characteristic Unadjusted Adjusted (1) Ziprasidone (N=697) Ziprasidone (N=696) (N=979,614) Age, mean () 25.00 6.20 24.01 5.77 0.17 25.05 6.26 25.07 6.10-0.01 Year of delivery, N (%) 2000-2002 15 2.15 176,598 13.26-0.43 15 2.16 23,785 1.80 0.03 2003-2005 162 23.24 437,846 32.87-0.22 162 23.28 300,180 22.69 0.01 2006-2007 200 28.69 302,404 22.70 0.14 200 28.74 378,766 28.63 0.00 2008-2010 320 45.91 415,062 31.16 0.31 319 45.83 620,043 46.87-0.02 Race, N (%) White 431 61.84 532,864 40.01 0.45 431 61.93 890,668 67.33-0.11 Black 172 24.68 446,430 33.52-0.20 171 24.57 274,099 20.72 0.09 Hispanic 35 5.02 8,830 0.66 0.26 35 5.03 52,650 3.98 0.05 Other or unknown 59 8.46 156,027 11.71-0.11 59 8.48 105,357 7.96 0.02 Multiple gestation, N (%) 26 3.73 45,188 3.39 0.02 26 3.74 48,810 3.69 0.00 Antipsychotic indications, N (%) Bipolar disorder 293 42.04 9,548 0.72 1.17 292 41.95 539,554 40.79 0.02 Psychosis 50 7.17 36,912 2.77 0.20 50 7.18 73,558 5.56 0.07 Depression 217 31.13 62,931 4.72 0.73 217 31.18 456,439 34.51-0.07 Schizophrenia 110 15.78 873 0.07 0.61 109 15.66 136,413 10.31 0.16 Anxiety 184 26.40 41,813 3.14 0.69 184 26.44 392,040 29.64-0.07 ADHD 58 8.32 9,965 0.75 0.37 58 8.33 112,237 8.48-0.01 Other psychiatric disorders 90 12.91 14,930 1.12 0.47 89 12.79 160,117 12.10 0.02
Characteristic Unadjusted Adjusted (1) Ziprasidone (N=697) Ziprasidone (N=696) (N=979,614) Other mental and neurological conditions, N (%) Adjustment disorder 12 1.72 13,153 0.99 0.06 12 1.72 25,827 1.95-0.02 Delirium 10 1.43 768 0.06 0.16 10 1.44 16,917 1.28 0.01 Sleep disorders 35 5.02 8,830 0.66 0.26 34 4.89 69,997 5.29-0.02 Personality disorder 33 4.73 127,722 9.59-0.19 33 4.74 54,652 4.13 0.03 Alcohol abuse or 27 3.87 6,669 0.50 0.23 27 3.88 48,597 3.67 0.01 dependence Chronic fatigue 50 7.17 36,912 2.77 0.20 50 7.18 107,101 8.10-0.03 syndrome Drug abuse or 65 9.33 16,256 1.22 0.37 65 9.34 115,424 8.73 0.02 dependence Epilepsy or convulsions 35 5.02 8,830 0.66 0.26 35 5.03 65,981 4.99 0.00 Migraine/headache 103 14.78 92,100 6.91 0.25 102 14.66 203,691 15.40-0.02 Chronic maternal illness, N (%) Diabetes 25 3.59 23,780 1.79 0.11 25 3.59 42,059 3.18 0.02 Hypertension 27 3.87 6,669 0.50 0.23 27 3.88 53,215 4.02-0.01 Obesity 33 4.73 127,722 9.59-0.19 33 4.74 64,464 4.87-0.01 Renal disease * * 395 0.03 0.08 * * 5,280 0.40 0.00 Smoking 79 11.33 39,418 2.96 0.33 79 11.35 149,265 11.28 0.00 Other psychotropic medications, N (%) Anticonvulsants 252 36.15 21,055 1.58 0.98 251 36.06 477,640 36.11 0.00
Characteristic Unadjusted Adjusted (1) Ziprasidone (N=697) Ziprasidone (N=696) (N=979,614) Antidepressants 499 71.59 107,131 8.04 1.71 498 71.55 1,078,761 81.55-0.24 Anxiolytics 27 3.87 6,669 0.50 0.23 27 3.88 53,475 4.04-0.01 Barbituates 19 2.73 12,992 0.98 0.13 19 2.73 39,901 3.02-0.02 Benzodiazepines 220 31.56 35,889 2.69 0.83 220 31.61 467,985 35.38-0.08 Other hypnotics 159 22.81 43,700 3.28 0.61 158 22.70 316,368 23.92-0.03 Stimulants for ADHD 69 9.90 7,789 0.58 0.43 69 9.91 140,157 10.60-0.02 Other medications, N (%) Antidiabetics 15 2.15 8,973 0.67 0.13 15 2.16 26,952 2.04 0.01 Antihypertensives 62 8.90 28,278 2.12 0.30 62 8.91 128,358 9.70-0.03 Buphrenophine * * 12,170 0.91 0.02 * * 16,905 1.28-0.01 Insulin * * 768 0.06 0.16 * * 20,206 1.53-0.01 Methadone * * 1,581 0.12-0.05 * * 7 0.00 0.00 Naloxone * * 1,134 0.09 0.15 * * 18,896 1.43-0.01 Naltrexone * * 14,149 1.06-0.09 * * 3,187 0.24 0.01 Opioids 271 38.88 254,845 19.13 0.45 270 38.79 549,232 41.52-0.06 Suspected teratogens, N 123 17.65 110,453 8.29 0.28 123 17.67 238,136 18.00-0.01 (%) (2) N of distinct prescriptions, 4.89 4.03 1.63 2.31 0.99 4.90 3.96 5.35 4.09-0.11 excluding APMs, mean () Patients hospitalized, N 67 9.61 48,687 3.66 0.24 66 9.48 112,245 8.49 0.03 (%) Proxies for severity Comorbidity Index, mean 1.47 1.69 0.89 1.39 0.37 1.49 1.67 1.54 1.84-0.04
Characteristic Unadjusted Adjusted (1) () N of diagnoses, mean () N of outpatient physician visits, mean () N of hospitalizations, mean () N of days hospitalized, mean () N of ER visits, mean Ziprasidone (N=697) Ziprasidone (N=696) (N=979,614) 5.92 4.87 2.56 3.10 0.83 5.88 4.82 6.39 4.94-0.09 9.53 10.55 2.80 3.95 0.84 9.46 10.53 8.69 8.79 0.09 0.12 0.43 0.04 0.24 0.22 0.11 0.42 0.10 0.36 0.04 0.51 1.86 0.13 0.93 0.25 0.47 1.81 0.48 2.33 0.01 1.07 3.60 0.31 0.81 0.29 1.09 3.74 0.94 1.76 0.04 () *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy (1) All characteristics included in PS. To account for PS, the untreated observations were weighted using the distribution of the treated among 50 PS strata. Observations from the non-overlapping regions of the PS distributions were trimmed. (2) Suspected teratogens included fluconazole, methimazole, danazol, propylthiouracil, progestins, and corticosteroids. Women exposed to known teratogens (warfarin, angiotensin converting enzyme inhibitors, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) were excluded from the cohort. : ard deviation; Diff: ardized Difference Medicaid Analytic extract, 2000-2010.
etable 10. Relative Risks Comparing the Risk for Malformations Between AP-Exposed and Unexposed Women Exposure Group Exposed Unexposed RR 95% CI Outcomes Total N Outcomes Total N UNADJUSTED Congenital malformation overall Typical antipsychotics 28 733 43,494 1,331,910 1.17 (0.81, 1.68) Atypical antipsychotics 412 9,258 43,494 1,331,910 1.36 (1.24, 1.50) Aripiprazole 75 1,756 43,494 1,331,910 1.31 (1.05, 1.63) Olanzapine 59 1,394 43,494 1,331,910 1.30 (1.01, 1.66) Quetiapine 182 4,221 43,494 1,331,910 1.32 (1.15, 1.52) Risperidone 80 1,566 43,494 1,331,910 1.56 (1.26, 1.94) Ziprasidone 26 697 43,494 1,331,910 1.14 (0.78, 1.67) Cardiac Malformation Typical antipsychotics * 733 15,405 1,331,910 1.18 (0.64, 2.18) Atypical antipsychotics 150 9,258 15,405 1,331,910 1.40 (1.19, 1.64) Aripiprazole 27 1,756 15,405 1,331,910 1.33 (0.91, 1.93) Olanzapine 20 1,394 15,405 1,331,910 1.24 (0.80, 1.92) Quetiapine 70 4,221 15,405 1,331,910 1.43 (1.14, 1.81) Risperidone 29 1,566 15,405 1,331,910 1.60 (1.12, 2.30) Ziprasidone * 697 15,405 1,331,910 1.12 (0.58, 2.14) ADJUSTED FOR PSYCHIATRIC INDICATIONS Congenital malformation overall Typical antipsychotics 27 668 43,478 1,331,449 1.00 (0.69, 1.45) Atypical antipsychotics 409 9,240 43,493 1,331,896 1.12 (1.02, 1.23) Aripiprazole 73 1,750 43,247 1,325,710 1.04 (0.83, 1.30) Olanzapine 56 1,335 43,413 1,329,948 1.05 (0.82, 1.36) Quetiapine 182 4,213 43,478 1,331,557 1.09 (0.95, 1.26)
Exposure Group Exposed Unexposed RR 95% CI Outcomes Total N Outcomes Total N Risperidone 76 1,472 43,487 1,331,674 1.31 (1.05, 1.63) Ziprasidone 26 695 41,418 1,270,722 0.90 (0.61, 1.31) Cardiac Malformation Typical antipsychotics * 668 15,400 1,331,449 0.94 (0.49, 1.80) Atypical antipsychotics 148 9,240 15,405 1,331,896 1.15 (0.98, 1.35) Aripiprazole 26 1,750 15,307 1,325,710 1.06 (0.72, 1.55) Olanzapine 18 1,335 15,380 1,329,948 0.96 (0.61, 1.52) Quetiapine 70 4,213 15,398 1,331,557 1.18 (0.94, 1.49) Risperidone 28 1,472 15,402 1,331,674 1.39 (0.96, 2.01) Ziprasidone * 695 14,677 1,270,722 0.88 (0.46, 1.69) FULLY ADJUSTED Congenital malformation overall Typical antipsychotics 27 727 42,464 1,297,638 0.90 (0.62, 1.31) Atypical antipsychotics 410 9,237 42,529 1,289,826 1.05 (0.96, 1.16) Aripiprazole 74 1,752 33,090 957,012 0.95 (0.76, 1.19) Olanzapine 59 1,392 40,171 1,231,441 1.09 (0.85, 1.41) Quetiapine 181 4,213 39,291 1,161,955 1.01 (0.88, 1.17) Risperidone 80 1,565 42,443 1,290,485 1.26 (1.02, 1.56) Ziprasidone 26 696 33,500 979,614 0.88 (0.60, 1.28) Cardiac Malformation Typical antipsychotics * 727 15,015 1,297,638 0.75 (0.39, 1.43) Atypical antipsychotics 148 9,237 15,040 1,289,826 1.06 (0.90, 1.24) Aripiprazole 26 1,752 11,820 957,012 0.93 (0.64, 1.37) Olanzapine 20 1,392 14,316 1,231,441 0.99 (0.64, 1.53) Quetiapine 70 4,213 13,984 1,161,955 1.07 (0.85, 1.35)
Exposure Group Exposed Unexposed RR 95% CI Outcomes Total N Outcomes Total N Risperidone 29 1,565 15,062 1,290,485 1.26 (0.88, 1.81) Ziprasidone * 696 11,803 979,614 0.85 (0.44, 1.63) *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy Medicaid Analytic extract 2000-2010.
etable 11. Relative Risk for Malformations Between AP-Exposed and Unexposed Women: Sensitivity Analyses Using High-Dimensional PS and Restriction Exposure Group Exposed Unexposed RR 95% CI Outcomes Total N Outcomes Total N ADJUSTED FOR HIGH-DIMENSIONAL PROPENSITY SCORE (hdps) Congenital malformation overall Typical antipsychotics 27 726 37,396 1,137,048 0.93 (0.64, 1.35) Atypical antipsychotics 410 9,236 43,318 1,324,021 1.08 (0.98, 1.19) Aripiprazole 75 1,754 34,133 998,728 1.01 (0.81, 1.26) Olanzapine 59 1,391 41,614 1,278,002 1.11 (0.87, 1.43) Quetiapine 181 4,211 40,154 1,199,361 1.03 (0.89, 1.19) Risperidone 80 1,563 41,669 1,266,615 1.36 (1.10, 1.69) Ziprasidone 26 695 35,599 1,052,018 0.95 (0.65, 1.38) Cardiac Malformation Typical antipsychotics * 726 13,228 1,137,048 0.86 (0.45, 1.65) Atypical antipsychotics 148 9,236 15,341 1,324,021 1.10 (0.94, 1.30) Aripiprazole 27 1,754 12,170 998,728 1.07 (0.74, 1.56) Olanzapine 20 1,391 14,769 1,278,002 1.03 (0.67, 1.59) Quetiapine 69 4,211 14,283 1,199,361 1.10 (0.87, 1.39) Risperidone 29 1,563 14,778 1,266,615 1.38 (0.96, 1.98) Ziprasidone * 695 12,520 1,052,018 0.95 (0.49, 1.81) RESTRICTED TO SCHIZOPHRENIA, BIPOLAR DISORDER, PSYCHOSIS Congenital malformation overall Typical antipsychotics 16 384 474 11,705 1.03 (0.63, 1.68) Atypical antipsychotics 209 3,998 474 11,705 1.29 (1.10, 1.51) Aripiprazole 50 952 474 11,705 1.30 (0.98, 1.72) Olanzapine 33 650 474 11,705 1.25 (0.89, 1.77) Quetiapine 92 1,749 474 11,705 1.30 (1.05, 1.61) Risperidone 38 742 474 11,705 1.26 (0.92, 1.75)
Ziprasidone 15 426 474 11,705 0.87 (0.52, 1.44) Cardiac Malformation Typical antipsychotics * 384 171 11,705 1.25 (0.59, 2.64) Atypical antipsychotics 79 3,998 171 11,705 1.35 (1.04, 1.76) Aripiprazole 19 952 171 11,705 1.37 (0.85, 2.18) Olanzapine 12 650 171 11,705 1.26 (0.71, 2.26) Quetiapine 34 1,749 171 11,705 1.33 (0.92, 1.92) Risperidone 19 742 171 11,705 1.75 (1.10, 2.8) Ziprasidone * 426 171 11,705 0.80 (0.33, 1.94) RESTRICTED + ADJUSTED FOR OTHER INDICATIONS Congenital malformation overall Typical antipsychotics 14 335 471 11,568 0.95 (0.56, 1.60) Atypical antipsychotics 191 3,756 470 11,674 1.14 (0.97, 1.35) Aripiprazole 46 894 474 11,702 1.17 (0.87, 1.58) Olanzapine 31 598 473 11,677 1.25 (0.87, 1.78) Quetiapine 89 1,676 473 11,688 1.23 (0.98, 1.53) Risperidone 34 669 470 11,607 1.10 (0.79, 1.55) Ziprasidone 14 383 465 11,536 0.81 (0.48, 1.36) Cardiac Malformation Typical antipsychotics * 335 170 11,568 1.30 (0.62, 2.76) Atypical antipsychotics 75 3,756 170 11,674 1.28 (0.98, 1.67) Aripiprazole 19 894 171 11,702 1.43 (0.89, 2.29) Olanzapine 11 598 171 11,677 1.24 (0.68, 2.27) Quetiapine 34 1,676 171 11,688 1.33 (0.92, 1.92) Risperidone 18 669 170 11,607 1.72 (1.06, 2.78) Ziprasidone * 383 167 11,536 0.83 (0.34, 2.02) RESTRICTED + FULLY ADJUSTED Congenital malformation overall Typical antipsychotics 16 381 417 10,418 0.93 (0.57, 1.51) Atypical antipsychotics 209 3,995 471 11,606 1.16 (0.99, 1.35)
Aripiprazole 50 949 417 10,174 1.13 (0.86, 1.50) Olanzapine 33 648 446 10,949 1.19 (0.84, 1.67) Quetiapine 92 1,747 464 11,440 1.13 (0.92, 1.41) Risperidone 38 740 463 11,497 1.19 (0.86, 1.64) Ziprasidone 15 425 446 10,971 0.84 (0.51, 1.39) Cardiac Malformation Typical antipsychotics * 381 152 10,418 0.91 (0.43, 1.91) Atypical antipsychotics 79 3,995 169 11,606 1.21 (0.93, 1.57) Aripiprazole 19 949 154 10,174 1.13 (0.71, 1.80) Olanzapine 12 648 161 10,949 1.23 (0.69, 2.19) Quetiapine 34 1,747 168 11,440 1.17 (0.81, 1.67) Risperidone 19 740 167 11,497 1.64 (1.03, 2.62) Ziprasidone * 425 159 10,971 0.75 (0.31, 1.81) *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy Medicaid Analytic extract 2000-2010.
etable 12. Fully Adjusted Relative Risk for Malformations Between AP-Exposed and Unexposed Women: Sensitivity Analyses Varying Exposure and Outcome Definition Exposure Group Exposed Unexposed RR 95% CI Outcomes Total N Outcomes Total N EXPOSURE DEFINED AS FILLING AT LEAST TWO PRESCRIPTIONS DURING THE FIRST TRIMESTER Congenital malformation overall Typical antipsychotics * 212 28,578 860,458 0.80 (0.39, 1.66) Atypical antipsychotics 177 3,798 40,866 1,226,901 1.09 (0.94, 1.25) Aripiprazole 27 555 25,221 699,847 1.08 (0.75, 1.56) Olanzapine 19 501 37,250 1,143,869 0.97 (0.62, 1.51) Quetiapine 84 1,851 39,792 1,182,806 1.08 (0.87, 1.33) Risperidone 27 473 30,941 933,940 1.46 (1.01, 2.10) Ziprasidone 12 267 31,332 914,337 1.14 (0.66, 1.98) Cardiac Malformation Typical antipsychotics * 212 10,023 860,458 0.74 (0.24, 2.29) Atypical antipsychotics 70 3,798 14,502 1,226,901 1.17 (0.93, 1.47) Aripiprazole * 555 9,041 699,847 1.02 (0.53, 1.94) Olanzapine * 501 13,312 1,143,869 1.13 (0.59, 2.17) Quetiapine 33 1,851 14,171 1,182,806 1.13 (0.81, 1.59) Risperidone 13 473 10,913 933,940 1.87 (1.09, 3.19) Ziprasidone * 267 11,071 914,337 1.04 (0.39, 2.75) EXPOSURE DEFINED AS DAYS SUPPLY OVERLAP WITH THE FIRST TRIMESTER Congenital malformation overall Typical antipsychotics 27 751 42,688 1,304,624 0.89 (0.62, 1.29) Atypical antipsychotics 414 9,290 42,530 1,289,545 1.06 (0.97, 1.17) Aripiprazole 78 1,858 33,219 961,596 0.95 (0.77, 1.18) Olanzapine 64 1,459 40,392 1,238,011 1.14 (0.9, 1.45) Quetiapine 188 4,379 39,567 1,173,446 1.01 (0.88, 1.16) Risperidone 91 1,719 42,643 1,298,220 1.31 (1.07, 1.6) Ziprasidone 28 760 33,498 972,490 0.85 (0.59, 1.23)
Cardiac Malformation Typical antipsychotics * 751 15,081 1,304,624 0.78 (0.41, 1.5) Atypical antipsychotics 149 9,290 15,042 1,289,545 1.06 (0.91, 1.25) Aripiprazole 28 1,858 11,857 961,596 0.96 (0.66, 1.38) Olanzapine 21 1,459 14,389 1,238,011 1.00 (0.65, 1.53) Quetiapine 73 4,379 14,072 1,173,446 1.09 (0.86, 1.36) Risperidone 35 1,719 15,128 1,298,220 1.38 (0.99, 1.92) Ziprasidone * 760 11,815 972,490 0.83 (0.45, 1.54) OUTCOME DEFINED BASED ON CODES IN INFANT CLAIMS ONLY Congenital malformation overall Typical antipsychotics 22 727 37,660 1,297,638 0.79 (0.52, 1.19) Atypical antipsychotics 377 9,237 37,724 1,289,826 1.04 (0.95, 1.15) Aripiprazole 69 1,752 29,414 957,012 0.95 (0.75, 1.19) Olanzapine 53 1,392 35,570 1,231,441 1.07 (0.82, 1.40) Quetiapine 164 4,213 34,911 1,161,955 0.99 (0.85, 1.15) Risperidone 74 1,565 37,638 1,290,485 1.26 (1.01, 1.57) Ziprasidone 25 696 29,829 979,614 0.90 (0.61, 1.32) Cardiac Malformation Typical antipsychotics * 727 12,849 1,297,638 0.73 (0.37, 1.45) Atypical antipsychotics 141 9,237 12,879 1,289,826 1.11 (0.94, 1.31) Aripiprazole 25 1,752 10,121 957,012 0.96 (0.65, 1.42) Olanzapine 18 1,392 12,204 1,231,441 1.01 (0.64, 1.60) Quetiapine 67 4,213 11,960 1,161,955 1.13 (0.89, 1.43) Risperidone 27 1,565 12,890 1,290,485 1.30 (0.89, 1.88) Ziprasidone * 696 10,142 979,614 0.91 (0.48, 1.75) *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy Medicaid Analytic extract 2000-2010.
etable 13. Fully Adjusted Relative Risk for Malformations Between AP-Exposed and Unexposed Women Stratified by Low, Medium, and High Dose Exposure Group Exposed Unexposed RR (95% CI) Outcomes Total N Outcomes Total N PS-adjusted Congenital malformation overall Aripiprazole Low dose 25 618 31,026 834,482 1.23 (0.88, 1.71) Medium dose 31 516 39,127 1,025,794 0.69 (0.43, 1.12) High dose 15 618 34,407 880,641 0.94 (0.64, 1.38) Olanzapine Low dose 31 670 39,127 1,200,272 1.19 (0.85, 1.68) Medium dose 15 386 34,407 1,061,542 0.99 (0.61, 1.63) High dose 13 336 38,750 1,196,848 1.01 (0.59, 1.72) Quetiapine Low dose 47 1,279 35,523 1,026,741 0.90 (0.68, 1.19) Medium dose 57 1,093 37,424 1,092,576 1.25 (0.97, 1.61) High dose 78 1,846 34,155 972,415 0.97 (0.78, 1.21) Risperidone Low dose 24 407 33,808 988,963 1.42 (0.96, 2.09) Medium dose 24 532 37,483 1,126,638 1.13 (0.76, 1.67) High dose 32 609 35,823 1,094,959 1.36 (0.97, 1.90) Ziprasidone Low dose 12 229 30,740 888,561 1.29 (0.74, 2.24) Medium dose * 225 25,540 732,642 0.86 (0.44, 1.71) High dose * 242 30,295 889,183 0.59 (0.27, 1.29) Cardiac Malformation
Exposure Group Exposed Unexposed RR (95% CI) Outcomes Total N Outcomes Total N PS-adjusted Aripiprazole Low dose * 618 11,168 834,482 0.97 (0.50, 1.85) Medium dose * 516 13,854 1,025,794 0.98 (0.49, 1.96) High dose * 618 12,267 880,641 0.93 (0.48, 1.77) Olanzapine Low dose * 670 13,854 1,200,272 0.83 (0.42, 1.66) Medium dose * 386 12,267 1,061,542 1.46 (0.74, 2.90) High dose * 336 13,806 1,196,848 0.81 (0.31, 2.15) Quetiapine Low dose 19 1,279 12,658 1,026,741 1.01 (0.64, 1.57) Medium dose 18 1,093 13,291 1,092,576 1.10 (0.69, 1.74) High dose 33 1,846 12,317 972,415 1.09 (0.78, 1.53) Risperidone Low dose * 407 12,017 988,963 0.95 (0.43, 2.10) Medium dose * 532 13,253 1,126,638 0.67 (0.28, 1.60) High dose 18 609 12,676 1,094,959 2.08 (1.32, 3.28) Ziprasidone Low dose * 229 10,784 888,561 1.53 (0.64, 3.64) Medium dose * 225 8,862 732,642 0.56 (0.14, 2.22) High dose * 242 10,790 889,183 0.58 (0.15, 2.32) *: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy Dose (mg) tertiles: Aripiprazole: <=5; 5 < Dose <= 10; >10 Olanzapine: <=5, 5 < dose <=10, >10
Quetiapine: <=50; 50 < Dose <= 100; >100 Risperidone: <1; 1<= to <2; >=2 Ziprasidone: <=40; 40 < Dose <= 80; >80 Medicaid Analytic extract 2000-2010.
etable 14. Relative Risk for Malformations Between Risperidone-Exposed and Unexposed Women Varying the Exposure Definition to Filling at Least 2 Prescriptions During The First Trimester Exposure Group Risperidone Exposed Unexposed RR (95% CI) Outcomes Total N Outcomes Total N Congenital malformation overall PS-adjusted 27 473 30,941 933,940 1.46 (1.01, 2.1) hdps-adjusted 27 477 40,341 1,244,862 1.50 (1.04, 2.16) Cardiac Malformation PS-adjusted 13 473 10,913 933,940 1.87 (1.09, 3.19) hdps-adjusted 13 477 14,215 1,244,862 1.90 (1.11, 3.25) Medicaid Analytic extract 2000-2010.
etable 15. Relative Risk for Malformations Between Risperidone Continuers and Discontinuers Using Different Definitions for Discontinuers Unexposed Group Exposed Unexposed RR (95% CI) Outcomes Total N Outcomes Total N UNADJUSTED Congenital malformation overall no Rx from start of pregnancy 44 897 73 1,757 1.18 (0.82, 1.70) no Rx from 4 weeks before pregnancy 44 897 50 1,097 1.08 (0.72, 1.60) no Rx from 6 weeks before pregnancy 44 897 35 804 1.13 (0.73, 1.74) no Rx from 8 weeks before pregnancy 44 897 19 505 1.30 (0.77, 2.21) Cardiac Malformation no Rx from start of pregnancy 18 897 26 1,757 1.36 (0.75, 2.46) no Rx from 4 weeks before pregnancy 18 897 18 1,097 1.22 (0.64, 2.34) no Rx from 6 weeks before pregnancy 18 897 11 804 1.47 (0.70, 3.09) no Rx from 8 weeks before pregnancy 18 897 * 505 2.53 (0.86, 7.44) PS-ADJUSTED Congenital malformation overall no Rx from start of pregnancy 44 895 72 1,737 1.00 (0.70, 1.43) no Rx from 4 weeks before pregnancy 41 882 50 1,089 1.13 (0.75, 1.71) no Rx from 6 weeks before pregnancy 41 878 35 799 1.12 (0.71, 1.75) no Rx from 8 weeks before pregnancy 40 866 19 496 1.64 (0.90, 2.98) Cardiac Malformation no Rx from start of pregnancy 18 895 26 1,737 0.85 (0.49, 1.46) no Rx from 4 weeks before pregnancy 15 882 18 1,089 1.31 (0.64, 2.68) no Rx from 6 weeks before pregnancy 15 878 11 799 1.70 (0.72, 4.01) no Rx from 8 weeks before pregnancy 15 866 * 496 2.46 (0.77, 7.87)
*: Cell sizes 10 (and their corresponding %) have been suppressed in accordance with CMS' cell size suppression policy Medicaid Analytic extract 2000-2010.
efigure 1. Study Diagram