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. Author manuscript; available in PMC: 2015 Feb 17.
Published in final edited form as: J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):512–521. doi: 10.1097/QAI.0000000000000211

Table 1.

Study Characteristics

Study Design;
setting		 Reporting
period		 Overall
study
size		 Numbers
receiving
CTX		 Indication HIV+ Dose Timing Duration Main drug
provided		 Other drugs Folate
Anderson et al, 201322 Hospital registry cohort & Danish Fertility Registry; Denmark 1997–2007 931,504 265 UTI 0 NR 1st Trimester NR TMP or TMP+SMX Sulfamethizole given to 34/265 NR
Anderson et al, 201323 Danish Fertility Registry; Denmark 1997–2005 521,267 402 UTI (assumed) 0 NR 12 weeks prior to pregnancy NR TMP or TMP+SMX NR 9
Angelakis et al, 201324 Retrospective cohort; France 2006–2011 46 17 Brucellosis NR NR Throughout pregnancy Variable (range 2 weeks – 6 months) TMP+SMX No NR
Bailey et al, 198325 RCT; New Zealand 1980–1982 44 44 Asymptomatic bacteriuria NR Either single dose CTX at 1.92g or 0.96g CTX BD (160 mg TM + 800mg SMX) for 5 days <30 weeks gestation Single dose or 5 days TMP+SMX No No
Brumfitt & Pursell, 197326 RCT; United Kingdom 1973 155 120 +35 referrals Bacteriuria 0 NR Only 10<16 weeks pregnant; 35 referrals exposed at time of conception Unclear TMP+SMX NR NR
Carcopino et al, 200727 Retrospective cohort; France 1991–2005 53 22 Q fever NR 320 mg TMP and 1600 mg SMX Throughout pregnancy Variable; mainly long-term >5 weeks TMP+SMX No No
Colley et al, 198228 Retrospective cohort; Australia 1978–1981 7371 209* Unclear 0 NR (most given “normal dose”) Throughout pregnancy NR TMP+SMX NR NR
Czeizel et al, 200129 Case-control study; Hungary 1980–1996 61016 794 Respiratory and UTI 0 80 mg TMP + 400 mg SMX 2 tablets x 2/3 daily on day 1, then 1 tablet x 2/day Throughout pregnancy 4 days TMP+SMX Various Cases 50%
Denoeud-Ndam et al, 201443 RCT; Benin 2009–2011 432 364 HIV (malaria prophylaxis) 432 160mg TMP + 800mg SMX 2nd and 3rd trimester Throughout pregnancy TMP+SMX Mefloquine (one arm, n=146); mefloquine, quinine or arthemeter–lumefantrine in case of malaria, depending on symptoms and levels of parasitaemia; antiretroviral therapy (32.7% AZT/3TC/EFV, 23.6% AZT/3TC/NVP, 18.1% D4T/3TC/NVP, 15.7% D4T/3TC/EFV) 5 mg folic acid (all)
Dow et al, 201344 RCT; Malawi 2004–2009 1236 768 HIV (malaria prophylaxis) 1236 160mg TMP + 800mg SMX BD 2nd and 3rd trimester Throughout pregnancy TMP+SMX Antiretroviral therapy (225/768) NR
Hernández-Díaz et al, 200030 Case-control study; USA and Canada 1976–1998 15319 66** UTI 0 NR −1 to +3 lunar months NR TMP+SMX Unclear 11% used daily peri-conceptional folic acid supplements
Hill et al, 198831 Case-control study; United Kingdom 1983 791*** 42 NR NR NR 3 months pre-conception & 1st trimester NR TMP+sulpha drugs NR Unclear
Jungman et al, 200132 Retrospective cohort; United Kingdom 1994–1999 195 29 HIV (prophylaxis) 29 NR 1st Trimester NR TMP+SMX No NR
Khan et al, 200133 Retrospective cohort; Saudi Arabia 1983–1995 92 40 Brucellosis 0 160mg TMP + 800mg SMX BD Throughout pregnancy >=4 weeks TMP+SMX (23)
TMP+SMX + rifampicin (17)		 17 also received rifampicin NR
Klement et al, 201445 RCT; Togo 2009–2012 264 126 (number analysed) HIV (malaria prophylaxis) 264 160mg TMP + 800mg SMX BD 2nd and 3rd trimester Throughout pregnancy TMP+SMX 300mg AZT or d4T, 3TC and NVP (depending on WHO Stage); malaria treatment where indicated Yes (all)
Matok et al, 200934**** Retrospective cohort; Israel 1998–2007 84823 346 “primarily” UTI NR NR 1st trimester Mean 7.4 days for all DHRI TMP+SMX 2 women methotrexate only, 1 sulfasalazine only NR
Meijer et al, 200535 Case-Control study; Netherlands 1997–2002 2217 15 Unclear NR NR 1st Trimester Unclear TMP 7 TMP only, 2 TMP+sulfoxamide, 3 sulfasalazine ~24% all cases and controls
Michigan Medicaid surveillance study, 200336 Surveillance; USA Unclear 2296 2296 Unclear NR NR NR NR TMP+SMX NR NR
Roushan, et al 201137 Retrospective case series; Iran 2000–2010 19 14 Brucellosis NR NR Throughout pregnancy 2 months TMP+SMX Rifampicin (all women) NR
Santos et al, 201138 Case-control (prospectively collected data); Canada 1998–2003 63338 214 Unclear NR NR Throughout pregnancy Variable TMP+SMX NR NR
Valentini et al, 200939 Retrospective hospital case review; Italy 2009 (published) 76 76 Toxoplasmosis NR 160mg TMP + 800mg SMX BD 2nd and 3rd trimester (Start at least after week 14, and stop 2 weeks before delivery) Variable – up to 24 weeks TMP+SMX Spiramycin (all women) Yes (all)
Walter et al, 20063 Cohort nested within an RCT; Zambia 2001–2004 255 67 HIV (prophylaxis) 67 80mg TMP + 400mg SMX BD Delayed until 2nd trimester Ongoing; dependent on CD4 TMP+SMX Chloroquine (2002) then sulfadoxine-pyrimethamine (2003) ART 800 mg (all women)
Wen et al, 200840 Retrospective cohort; Canada 1980–2000 74807 DHRI: 11386 TMP-SMX: 12546 NR (any exposure but mostly UTI) NR NR Pre-conception period and throughout pregnancy NR TMP+SMX No NR
Yaris et al, 200441 Toxicology Information and Follow-up Service; Turkey 1999–2004 511 11 UTI NR TM-SMX 160–800 mg for 7–10 days (2 cases with Gentamicin) 1st trimester 7–10 days TMP+SMX Gentamicin in 2 cases NR (unlikely)

CTX, cotrimoxazole; 3TC, lamivudine; ART, antiretroviral therapy; AZT, zidovudine; BD, twice daily; DHRI dihydrofolate reductase inhibitors; NR, not reported; NVP, nevirapine; RCT Randomised control trial; TMP+SMX, cotrimoxazole (TMP trimethoprim; SMX sulfamethoxizole); UTI, urinary tract infection

*

127 additional patients given sulfamethizole alone

**

Trimethoprim, triamterene, and sulfasalazine. Exact numbers not given

***

Cases only

****

Includes fetal anomalies diagnosed via prenatal ultrasound