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PEDIATRICS Volume 146, Number 1, July 2020 1 SUPPLEMENTAL TABLE 3 Diagnostic and Procedure Codes Defining Cohort Characteristics Variable Diagnostic or Procedure Codes Deliveries CPT codes: 01960, 01961, 01962, 01963, 01967, 01968, 01969, 59050, 59051, 59400, 59409, 59410, 59412, 59414, 59430, 59510, 59514, 59515, 59525, 59610, 59612, 59614, 59618, 59620, 59622, 99436, and 99440; ICD-9 procedure codes: 72, 72.0, 72.1, 72.2, 72.21, 72.29, 72.3, 72.31, 72.39, 72.4, 72.5, 72.51, 72.52, 72.53, 72.54, 72.6, 72.7, 72.71, 72.79, 72.8, 72.9, 73, 73.0, 73.01, 73.09, 73.1, 73.2, 73.21, 73.22, 73.3, 73.4, 73.5, 73.51, 73.59, 73.6, 73.8, 73.9, 73.91, 73.92, 73.93, 73.94, 73.99, 74, 74.0, 74.1, 74.2, 74.4, 74.9, 74.91, 74.99, and 75.4; ICD-10 procedure codes: 10D07Z3, 10D07Z4, 10D07Z5, 10D07Z6, 10D07Z7, 10S07ZZ, 10900ZC, 10903ZC, 10904ZC, 10907ZC, 10908ZC, 0U7C7ZZ, 10J07ZZ, 3E0P7GC, 10E0XZZ, 0W8NXZZ, 10907ZA, 10908ZA, 10S0XZZ, 10D07Z8, 10D00Z0, 10D00Z1, 10D00Z2, 10A00ZZ, 10A03ZZ, 10A04ZZ, 10D17ZZ, and 10D18ZZ; ICD-9 diagnosis codes: V27.x and V30.xx–V39.xx; ICD-10 diagnosis codes: Z37–Z38 Depression ICD-9 diagnosis codes: 296.2x, 296.3x, 296.90x, 298.0x, 309.0x, 309.1x, and 311.x; ICD-10 diagnosis codes: F32.x–F34.x, F38.x, and F39.x, Anxiety ICD-9 diagnosis codes: 300.0.x and 300.4x; ICD-10 diagnosis codes: F40–F48 Other mental health ICD-9 diagnosis codes: 295.x, 296.0x–296.1x, 296.4x–296.8x, 297.xx, 298.1x–298.9x, 300.1x–300.3x, 300.5x–300.9x, 301.x, 308.x, 309.2x–309.9x, 312.x, and 648.4x; ICD-10 diagnosis codes: F20.x–F29.x, F30.x–F31.x, F40.x, F42.x–F45.x, F48.x, F60.x–F61.x, F91.x–F92.x, O99.34x, O90.6x, and F53.x Pain disorder ICD-9 diagnosis codes: 338.xx, 346.xx, 780.96, 729.1x, 531.x–534.x, 555.x, 556.x, 564.1x, 710.0x, and 714.x; ICD-10 diagnosis codes: G43x, G89.x, R52.x, M79.x, M05.x, M06.x, M08.x, M32.1x, M32.8x, M32.9x, K25.x–K28.x, K50.x–K51.x, and K58.x Sleep disorder ICD-9 diagnosis codes: 307.41, 307.42, 307.45, 307.49, and 780.50–780.52; ICD-10 diagnosis codes: F51.0x, F51.8x, F51.9x, G47.0x, and G47.2x Antidepressants SSRIs: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; SNRIs: levomilnacipran, venlafaxine, duloxetine, and desvenlafaxine; bupropion; other: vilazodone, vortioxetine, reboxetine, mirtazapine, nefazodone, selegiline, mianserin, reboxetine, trazodone, amoxapine, maprotiline, isocarboxazid, phenelzine, tranylcypromine, moclobemide, amytriptyline, clomipramine, desipramine, dothiepin, doxepin, imipramine, nortriptyline, protriptyline, and trimipramine Benzodiazepines Alprazolam, bromazepam, chlordiazepoxide, clonazepam, clorazepate, clobazam, diazepam, estazolam, flurazepam, halazepam, lorazepam, nitrazepam, oxazepam, prazepam, temazepam, and triazolam Antipsychotics Acetophenazine, acetylpromazine maleate, aripiprazole, butaperazine maleate, chlorproethazine, chlorpromazine, chlorprothixene, clothiapine, clozapine, cyamemazine, dixyrazine, droperidol, fluanisone, flupenthixol or flupentixol, fenazine, fluphenazine decanoate, fluphenazine enanthate, asenapine, fluspirilene, haloperidol, loxapine succinate, melperone, mepazine, mesoridazine besylate, methotrimeprazine, metofenazate difumarate, metopimazine, molindone, moperone, olanzapine, paliperidone, perazine, perphenazine, perphenazine enanthate, cariprazine, pimozide, pipamperone, piperacetazine, prochlorperazine, prochlorperazine dimaleate, prochlorperazine edisylate, prochlorperazine maleate, prochlorperazine mesylate, promazine, propericiazine, propiomazine, quetiapine, risperidone, sulpiride, tetrabenazine, thiethylperazine, thiethylperazine maleate, thiopropazate, thioproperazine, thioridazine, thiothixene, tiapride, trifluoperazine, triflupromazine, iloperidone, veralipride, ziprasidone, zuclopenthixol, zotepine, and pimavanserin Hypertension ICD-9 diagnosis codes: 401.x–405.x; ICD-10 diagnosis codes: I10.x–I15.x Major cardiac malformations At least 2 of the following ICD-9 diagnosis codes: 745, 745.0x, 745.1x, 745.10, 745.11, 745.12, 745.19, 745.2x, 745.3x, 745.6x, 745.60, 745.61, 745.69, 745.7x, 745.8x, 745.9x, 746, 746.00, 746.1x, 746.2x, 746.3x, 746.5x, 746.7x, 746.8, 746.80, 746.82, 746.84, 746.85, 746.86, 746.87, 746.89, 747, 747.1x, 747.10, 747.11, 747.2x, 747.20, 747.21, 747.22, 747.29, 747.4x, 747.40, 747.41, 747.42, 747.49, 747.83, 746.9x, 746.01, 746.09, 746.83, 747.3x and no preterm delivery codes in first 60 d after delivery, 746.02 and no preterm delivery codes in first 60 d after delivery, and 745.4x; and ICD-10 diagnosis codes: Q20–Q28. At least 1 of the previous codes plus 1 of the following ICD-9 procedure codes: 35.x, 36.x, 37.x (except 37.94), 38.x (except 38.18, 38.91, 38.92, 38.93, 38.94, 38.95, 38.98,

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SUPPLEMENTAL TABLE 3 Continued Variable Diagnostic or Procedure Codes and 38.99), 39.x (except 39.27, 39.50, 39.95, and 39.98); and CPT codes: 00560, 00561, 00563, 33300–35190, 92992, 92993, 93530, 93531, 93532, and 93533 Newborn respiratory distress ICD-9 diagnosis codes: 769, 770.6, and 770.8; ICD-10 diagnosis code: P22.0 Preterm delivery ICD-9 diagnosis codes: 644.2x, 765.0x, 765.1x, and 765.2; ICD-10 diagnosis codes: P07.2x, P07.3x (from maternal records) Exclusions for known teratogens Chromosomal anomaly: ICD-9 diagnosis codes: 758.x, 759.81, 759.826, and 759.83; ICD-10 diagnosis codes: Q90x–Q99x. Known human teratogen in ﬁrst 12 wk gestation: acetretin, aminopterin, carbamazepine, isotretinoin, lanalomide, lithium, misoprostol, methotrexate, mycophenolate, thalidomide, topiramate, valporic acid, warafarin

SUPPLEMENTAL TABLE 4 Cell Sizes and Unadjusted Effect Estimates for 12-Week Trajectory Assignments and the Risk of Major Malformations na Major % Major Crude RR (95% CI) Malformations Malformations Low use with reduction (A) 6780 99 1.46 Reference Low sustained use (B) 3532 62 1.76 1.20 (0.88–1.65) Moderate use with reduction (C) 1866 34 1.82 1.25 (0.85–1.84) Moderate sustained use (D) 2202 52 2.36 1.61 (1.16–2.25) High sustained use (E) 525 13 2.48 1.70 (0.96–3.00) Depression and no antidepressant use 4906 93 1.90 Reference Low use with reduction (A) 6780 99 1.46 0.77 (0.58–1.02) Low sustained use (B) 3532 62 1.76 0.93 (0.67–1.27) Moderate use with reduction (C) 1866 34 1.82 0.96 (0.65–1.42) Moderate sustained use (D) 2202 52 2.36 1.25 (0.89–1.74) High sustained use (E) 525 13 2.48 1.31 (0.76–2.32) Anxiety and no antidepressant use 9362 191 2.04 Reference Low use with reduction (A) 6780 99 1.46 0.72 (0.56–0.91) Low sustained use (B) 3532 62 1.76 0.86 (0.65–1.14) Moderate use with reduction (C) 1866 34 1.82 0.89 (0.62–1.28) Moderate sustained use (D) 2202 52 2.36 1.16 (0.86–1.57) High sustained use (E) 525 13 2.48 1.21 (0.70–2.11) a A total of 136 were excluded because of a teratogen or chromosomal anomaly in the primary model, 179 were excluded in the depression reference model, and 180 were excluded in the anxiety reference model.

SUPPLEMENTAL TABLE 5 Cell Sizes and Unadjusted Effect Estimates for 35-Week Trajectory Assignments and the Risk of Preterm Birth n Preterm % Preterm Crude RR (95% CI) Birth Birth Low use with reduction (A) 7622 769 10.09 Reference Low sustained use (B) 3170 367 11.58 1.15 (1.02–1.29) Moderate use with reduction (C) 1907 191 10.02 0.99 (0.85–1.15) Moderate sustained use (D) 1918 287 14.96 1.48 (1.31–1.68) High sustained use (E) 424 102 24.06 2.39 (1.99–2.86) Depression and no antidepressant use 4949 576 11.64 Reference Low use with reduction (A) 7622 769 10.09 0.86 (0.77–0.95) Low sustained use (B) 3170 367 11.58 0.98 (0.86–1.11) Moderate use with reduction (C) 1907 191 10.02 0.85 (0.73–0.99) Moderate sustained use (D) 1918 287 14.96 1.27 (1.11–1.45) High sustained use (E) 424 102 24.06 2.04 (1.70–2.46) Anxiety and no antidepressant use 9406 1031 10.96 Reference Low use with reduction (A) 7622 769 10.09 0.91 (0.83–0.99) Low sustained use (B) 3170 367 11.58 1.04 (0.93–1.17) Moderate use with reduction (C) 1907 191 10.02 0.91 (0.78–1.05) Moderate sustained use (D) 1918 287 14.96 1.35 (1.19–1.52) High sustained use (E) 424 102 24.06 2.18 (1.82–2.60)

PEDIATRICS Volume 146, Number 1, July 2020 3 SUPPLEMENTAL TABLE 6 Cell Sizes and Unadjusted Effect Estimates for 35-Week Trajectory Assignments and the Risk of Neonatal Respiratory Distress n Respiratory % Respiratory Crude RR (95% CI) Distress Distress Low use with reduction (A) 7622 564 7.40 Reference Low sustained use (B) 3170 331 10.44 1.41 (1.24–1.61) Moderate use with reduction (C) 1907 185 9.70 1.31 (1.12–1.54) Moderate sustained use (D) 1918 256 13.35 1.81 (1.57–2.08) High sustained use (E) 424 86 20.28 2.74 (2.24–3.35) Depression and no antidepressant use 4949 360 7.27 Reference Low use with reduction (A) 7622 564 7.40 1.02 (0.90–1.15) Low sustained use (B) 3170 331 10.44 1.43 (1.24–1.65) Moderate use with reduction (C) 1907 185 9.70 1.33 (1.13–1.58) Moderate sustained use (D) 1918 256 13.35 1.84 (1.58–2.14) High sustained use (E) 424 86 20.28 2.78 (2.25–3.44) Anxiety and no antidepressant use 9406 715 7.60 Reference Low use with reduction (A) 7622 564 7.40 0.97 (0.87–1.08) Low sustained use (B) 3170 331 10.44 1.37 (1.21–1.55) Moderate use with reduction (C) 1907 185 9.70 1.28 (1.09–1.49) Moderate sustained use (D) 1918 256 13.35 1.75 (1.54–2.01) High sustained use (E) 424 86 20.28 2.66 (2.18–3.25)

SUPPLEMENTAL TABLE 7 Effect Estimates for Trajectory Groups and the Risk of Adverse Perinatal Outcomes, Restricting to Women With SSRI Antidepressants Only na No. % Crude RR (95% CI) Adjusted RR (95% CI) Major cardiac malformations Low use with reduction (A) 5083 73 1.44 Reference Referenceb,c Low sustained use (B) 2732 48 1.76 1.22 (0.87–1.720) 1.23 (0.86–1.77)b,c Moderate use with reduction (C) 1041 21 2.02 1.33 (0.83–2.11) 1.47 (0.92–2.37)b,c Moderate sustained use (D) 1358 32 2.36 1.62 (1.09–2.24) 1.71 (1.14–2.57)b,c High sustained use (E) 219 ,11 ,5.0 Suppressed 2.09 (0.91–4.83)b,c Preterm birth Low use with reduction (A) 5636 560 9.94 Reference Referenceb,d Low sustained use (B) 2430 265 10.91 1.10 (0.96–1.26) 1.03 (0.90–1.18)b,d Moderate use with reduction (C) 1057 99 9.37 0.94 (0.77–1.15) 0.88 (0.72–1.08)b,d Moderate sustained use (D) 1206 163 13.52 1.36 (1.15–1.59) 1.22 (1.04–1.43)b,d High sustained use (E) 188 32 17.02 1.72 (1.24–2.38) 1.44 (1.05–1.97)b,d Respiratory distress Low use with reduction (A) 5636 395 7.01 Reference Referenceb,d Low sustained use (B) 2430 257 10.58 1.51 (1.30–1.75) 1.45 (1.25–1.68)b,d Moderate use with reduction (C) 1057 91 8.61 1.23 (0.99–1.53) 1.16 (0.94–1.44)b,d Moderate sustained use (D) 1206 169 14.01 2.00 (1.69–2.37) 1.85 (1.56–2.19)b,d High sustained use (E) 188 36 19.15 2.72 (2.02–3.68) 2.34 (1.74–3.14)b,d Cell sizes ,11 and corresponding crude RRs are suppressed per requirements of OptumLabs. a Eighty-four were excluded from the model because of exposure to a known teratogen or chromosomal anomaly. b The model was adjusted for maternal age; race and/or ethnicity; education; diagnosis of depression, anxiety, other mental health disorders, or pain disorder; and claims for benzodiazepines or antipsychotics. c Claims through 12 wk gestation. d Claims through 35 wk gestation.