DATA SUPPLEMENT
Fetotoxic risk of angiotensin receptor blockers exceeds that of angiotensin-converting enzyme inhibitors - an observational study
Corinna Weber-Schoendorfer, Angela Kayser, Tatjana Tissen-Diabaté, Ursula Winterfeld, Georgios Eleftheriou, Bernke te Winkel, Orna Diav-Citrin, Amanda Greenall, Maria Hoeltzenbein, Christof Schaefer
Figure S1: Flow diagram for angiotensin-converting enzyme inhibitor (ACE-I) exposed pregnancies – Teratology Information Service (TIS) Berlin
*There were three cases with ARB and ACE-I exposure >GW 12 6/7: One woman was
concomitantly treated with irbesartan and ramipril throughout pregnancy (P31). The second took enalapril and olmesartan until GW 15 (P70). The third one (R 111) was treated with ramipril from GW 17 6/7 until GW 18 4/7 and with azilsartan from before pregnancy until GW 23 4/7. All three cases were attributed to the ARB group.
Figure S2: Flow diagram for angiotensin II type 2 receptor blocker (ARB) exposed pregnancies – Teratology Information Service (TIS) Berlin
*There were three cases with ARB and ACE-I exposure >GW 12 6/7: One woman was
concomitantly treated with irbesartan and ramipril throughout pregnancy (P31). The second took enalapril and olmesartan until GW 15 (P70). The third one (R 111) was treated with ramipril from GW 17 6/7 until GW 18 4/7 and with azilsartan from before pregnancy until GW 23 4/7. All three cases were attributed to the ARB group.
Table S1: Cases with incomplete follow-up
P or R and TIS
Substance Exposure time
Outcome Reason for
exclusion R from BER ramipril 0 – 25 6/7 Hydrocephalus No further data.
Mother did not agree to provide further data.
R from BER captopril 0 - 16 Moebius-sequence Case from Brazil.
No further data.
Mother had denied taking misoprostol.
P from BER captopril 0 - 15 Healthy child No data on pregnancy course, no child data
R from JER candesartan 0 - 15 Suspected
oligohydramnios, kidney malformation in prenatal ultrasound. TOPFA ≥ 15 GW
No additional data to verify the kind of
malformation, no medical records, no detailed ultrasound report P from LAU candesartan 0 – 21 1/7 GW at call was 21 1/7: no
oligohydramnios. HIV positive mother with hypertension and kidney failure requiring
haemodialysis.
Candesartan, labetalol and carvedilol until GW 21 1/7. Nelfinavir, zidovudine and lamivudine until GW 22 1/7. Torasemide and amlodipine until
intrauterine death at GW 24 1/7
Case could not be allocated to either the fetopathy or the non-fetopathy group.
P: prospective; R: retrospective; TIS: Teratology Information Service; BER: Berlin; JER:
Jerusalem; LAU: Lausanne; GW: gestational week; TOPFA: termination of pregnancy for fetal anomalies.
Figure S3: Flowchart of renin-angiotensin system inhibitor (RAS-I) exposed pregnancies and fetopathy rates
Legend: ARB: angiotensin II type 2 receptor blocker; ACE-I: angiotensin-converting enzyme inhibitor; pro: prospectively ascertained cases; retro: retrospectively ascertained cases
Figure S4: Outcomes of renin-angiotensin system inhibitor exposed pregnancies without fetopathy
P: prospectively ascertained case; R: retrospectively ascertained case; * infant’s death ARB: angiotensin II type 2 receptor blocker; ACEI: angiotensin-converting enzyme inhibitor;
IUFD: intrauterine death; TOPFA: termination of pregnancy for fetal anomalies
Table S2: Overview of RAS-I symptoms in the 59 pregnancies with fetopathy (prospective and retrospective) (See also Figure 1)
Fetopathy symptoms
Symbol Frequency (all)
Frequency (subset ARBs)
Frequency (subset ACE-I) Oligo
/anhydramnios
a 53 50 3
Postnatal renal involvement
b 38 33 5
Contractures c 14 13 1
Widened sutures d 19 18 1
Lung hypoplasia e 11 11 0
Infant's thrombosis f 5 5 0
