Table 1.

Articles identified, divided by time of insertion for research question #1: Among IUD users, do women who breastfeed have an increased risk of adverse events (perforation, expulsion, infection, pain, or other adverse events) compared with women who do not breastfeed?

Author, location and funding source	Study design	Study population	IUD type	Outcomes, follow-up duration	Results	Strengths	Weaknesses	Quality
Immediate PPIUD insertion
Xu et al. [21], China, FHI and USAID	Cohort study (within RCT)	Women age 20–40 y, willing to receive immediate PP IUD Exposed: BF women (n=834) Unexposed: non-BF women (n=76)	CuT 380A	Expulsion	BF Expulsion rate at 6 mos; n (%) Yes 99 (11.9) p<0.05 No 17 (22.4)	Low attrition Adequate follow-up Outcome well defined		II-2, fair
Mixed immediate PP/interval IUD insertion or unspecified timing
Cole et al. [19]; 35 countries from Asia, Latin America, Middle East and Africa; IFRP, USAID	Cohort (pooled analysis from a series of multicentered trials)	Immediate PP insertion: Exposed: BF women receiving IUD (n=1022) Unexposed: non-BF women receiving IUD (n=817) Interval insertion: Exposed: BF women receiving IUD (n=282) Unexposed: non-BF women receiving IUD (n=150)	Cu-T	Expulsion Removal for bleeding or pain Follow-up 3 and 6 months	Immediate PP: BF Expulsion rate at 3 mos Removal bldg./pain at 3 mos Yes 10.9 2.3 No 7.3 0.7 Interval: BF Expulsion rate at 3 mos Removal bldg./pain at 3 mos Yes 2.1 0.0 No 2.6 4.3 No p values reported for 6-month time point; however, text says “no statistical differences” between any outcome at either time period for BF women compared to non-BF women.	Exposure well defined Large sample size for outcomes Adequate follow-up	No information about attrition Outcomes not defined Values not shown for 6-month time frame	II-2, fair
Heartwell, 1983 [9]  United States  NICHD	Multicenter case control	Cases (n=32): women with IUD perforation admitted to hospital for removal Controls (n=497): women with IUD in place admitted for acute self-limiting condition Exclusions: women <6 weeks PP	Many	Perforation Difficult removal (not further defined)	BF at time of IUD insertion* Perforation RR (95% CI) Difficult removal RR (95% CI) Yes 10.1 (4.9-20.6) 2.3 (1.1-4.4) No Ref Ref * Analysis limited to women with at least 1 prior live birth	Multiple hospitals	Results not reported by IUD type Unclear how BF status measured (recall) Perforation status not ascertained from controls Analysis not adjusted for potential confounders	II-2, poor
Chi and Kelly [16] andChietal. [17], 31 countries, FHI and USAID	Case–control analysis of large FHI international dataset March 1976–December 1981	Cases (n=41): women with IUD perforation Controls (n=41): women with no perforation matched by IUD type, inserter, center and date	Many	Perforation	Perforations in women in which BF status was known BF women N (%)* Cases (n=19) 3 (15.8) Controls (n=31) 1 (3.2) * No p value reported but authors stated “no significant difference” in risk of perforation for women breastfeeding at time of insertion compared to non-breastfeeding	Clearly defined outcomes and measurement clear	Small sample size Results not reported separately by IUD type No information about attrition Unclear how BF status measured	II-2, poor
Heinemann et al. [5], 6 European countries, Center for Epidemiology and Health Research, Germany, and Bayer	Prospective cohort	Women, at least 18 years, with a newly inserted IUD (n=61,448) Exposed: BF women (n=6645) Cu-IUD (n=2682) LNG IUD (n=3963) Unexposed: Non-BF women (n=54,803) Cu-IUD (n=15,688) LNGIUD (n=39,115)	Cu-IUD (many types) and LNG IUD LNG-IUD n= 43,078 (70.1%) Cu-IUD n=18,370 (29.9%)	Incidence of uterine perforation (self-reported, validated by physicians) Follow-up 12-months Noninferiority of LNG vs. Cu-IUD	Cu-IUD: BF Perforation incidence per 1000 women (95% CI) Perforation RR (95% CI) Yes 3.7 (1.8-6.8) 7.8 (2.8-21.4) No 0.5 (0.2-1.0) Ref All women 1.1 (0.7-1.7) -- LNG-IUD: BF Perforation incidence per 1000 women (95% CI) Perforation RR (95% CI) Yes 6.3 (4.1-9.3) 6.3 (3.8-10.5) No 1.0 (0.7-1.4) Ref All women 1.4 (1.1-1.8) -- Combined Cu-IUD and LNG-IUD: BF Perforation RR (95% CI) Yes 6.1 (3.9-9.6) No Ref BF Perforation incidence (≤36 wks PP at the time of IUD insertion) Perforation incidence (>36 wks PP at the time of IUD insertion) RR (95% CI) Yes 5.6 (3.9-7.9) 1.6 (0.0-9.1) 3.4 (0.5-24.8) No 1.7 (0.8-3.1) 0.7 (0.5-1.1) 2.3 (1.1-4.7) RR 95% CI 3.3 (1.6-6.7) 2.2 (0.3-16.3)	Large sample size Very low attrition (2%) Adequate follow-up Well defined exposure and outcome Results separated by IUD type	More than 30 types of Cu-IUDs were included.	II-2,good
Interval IUD insertions
Chi et al. [18] (insertional pain); 18centersinAsia, Latin America and the Middle East; FHI and USAID	Retrospective cohort (analysis oflarge FHI international IUD database) 1977–1986	Parous women at least 42 days PP whose last delivery was term, live, vaginal birth Exposed: BF women (n=3043) Unexposed: non-BF women (n=3450)	Many (Loops, Cu-Ts and multiloads: 55.7% Cu-IUD types that met inclusion criteria)	Mod/severe insertional pain Perforation Cervical laceration Syncope Any insertion-related adverse event	Cu-Ts: BF Syncope n (%)* Immediate perforation n(%)* Full 2 (0.12) 1 (0.06) No 0 (0.0) 1 (0.06) * p Values>.05 Results not separated by IUD type: BF Mod/severe pain at insertion RR (95% CI) Cervical laceration RR (95% CI) Any insertion related adverse event ** Full 0.47 (0.37-0.59) 0.72 (0.35-1.47) 0.46 (0.38-0.56) No ref ref ** Except perforation	Large sample size Adequate exposure and outcome definition Adequate follow-up	Multiple IUD types No information on attrition Some results not reported separately by IUD type	II-2, poor
Sastrawinata et al. [20], Indonesia, National Family Planning Coordinating Board of Indonesia USAID	Prospective cohort study (within an RCT)	Healthy women ages 18–40 aged years; ≥40 days PP Exposed: BF women (n=2237) Unexposed: non-BF women (n=608)	CuT 380A	Expulsion Removals for bleeding/pain Follow-up 24 months	BF Expulsion at 24 mos (Rate/100 women + SE) Removal for bleeding/pain at 24 mos (Rate/100 women + SE) Yes 6.0 ±0.9 1.6 ±0.5 No 6.9±1.7 4.1±1.4 (no p values reported, stated no statistically significant differences)	Long follow-up Low attrition Adequate definition and measurement of outcomes	Poor description of definition ofBF or how BF status may have changed over 24-month study time	II-2, fair
Wu [22], China	Prospective cohort	Healthy women with IUD Exposed: BF women (n=850) “early” 6–12 weeks PP (n=451) “late” 4–12 months PP (n=399) Unexposed: non-BF women; >6 weeks PP (n=2293)	CuT 380A	Perforation Infection Expulsion Removals for bleeding/pain Follow-up 12 month	No perforations No PID BF Expulsion at 12 mos (Rate/100 women)* Removal for bleeding/pain at 12 mos (Rate/100 women)* Yes; early 0.51 1.42 Yes; late 2.11 1.33 No 1.11 1.94 * p>.05 for all comparisons	Long follow-up Large sample size	Outcome assessment not well defined	II-2, fair
Studies from FHI’s randomized, multicenter clinical trial from May 1985 to September 1988. Women (N42 days PP) were randomized to either CuT 380A or another common IUD type used at multiple centers across 14 countries. Follow-up time occurred at 1, 3, 6 and 12 months.
Chi et al. [23] (performance ofCu)	Prospective cohort study (within larger RCT) Data from 1985 to 1986; CuT T380A users; 5 sites	Healthy women aged 18–40 years at least 42 days PP Exposed: BF women (n=559) Unexposed: non-BF women (n=590)	CuT 380A	Mod/severe pain at insertion Perforation Cervical laceration Expulsion Removal for bleeding/pain Follow-up: 6 months	BF Pain at insertion n(%) Perforation n(%) Cervical laceration n(%) Yes 5 (0.9) 0 (0.0) 5 (0.9) No 16 (2.7) 0 (0.0) 8 (1.4) p-value 0.026 -- 0.581 BF Expulsion at 6 mos (Rate*/100 women + SE) Removal for bleeding/pain at 6 mos (Rate*/100 women + SE)** Yes 2.5 ±0.7 0.4 ±0.4 No 2.8 ±0.7 3.2 ±0.8 * Adjusted for age. ** p<.05.	Large sample size Adequate follow-up Adequate exposure and outcome definition Single IUD type	Outcome assessment not well defined	II-2, good
Farr and Rivera [24]	Prospective cohort study (within larger RCT) Data from May 1985 to Sept. 1988; 25 sites; CuT 380A users	Healthy women aged 18–40 years at least 42 days PP Exposed: BF women (n=1032) Unexposed: non-BF women (n=1243)	CuT 380A	Pain at insertion Perforation Cervical laceration Expulsion Removal for bleeding/pain Follow-up: 12 months	BF Pain at insertion (%) Perforation (%) Cervical laceration (%) Yes 17.1 0 4.0 No 25.2 0 2.8 p-value 0.001 -- 0.156 BF Expulsion at 12 mos (Rate/100 women + SE)* Removal for bleeding/pain at 12 mos (Rate/100 women + SE)** Yes 3.9 ±0.7 2.9 ±0.6 No 2.8 ±0.5 5.1 ±0.7 * Not significant. ** p=.05.	Large sample size Long follow-up Low attrition Single IUD type Adequate definition of BF status		II-2, good
Zhang [25]; FHI, USAID	Nested case–control Data from 1985 to 1986; 13 sites	Healthy women aged 18–40 years at least 42 days PP Cases (n=143): women with IUD removal for bleeding/pain Controls (n=2023): women with IUD in place at last visit	TCu-200, TCu-220C or CuT 380A	Removal for bleeding/pain Follow-up: 12 months	BF Removal for bleeding/pain at 12 mos hazard ratio (95% CI)* Yes 0.75 (0.59-0.97 No Ref * Adjusted for center, age, parity, level of training of inserter, menstrual status and length from the external os to the fundus	Adequate sample size Long follow-up Adequate definition of BF status and outcome	Results not reported separately by IUD type No information on attrition for this subset	II-2, fair
Stanback and Grimes [26], USAID	Case–control analysis of multicenter FHI RCT. Data from1985 to 1986; 18 sites	Healthy women aged 18–40 years at least 42 days PP Cases (n=89): women with IUD removal for bleeding/pain Controls (n=20,536): women with IUD at 1 year	CuT 380A or Multiload 250	Removal for bleeding/pain Follow-up: 12 months	BF Removal for bleeding/pain at 12 mos OR (95% CI) Yes Ref No 2.8 (1.5-5.2)	Long follow-up Large sample size Adequately defined exposure and outcome	Results not reported separately by IUD type No mention of attrition rates for this subpopulation	II-2, poor
Rivera et al. [27]; FHI, USAID	Secondary cohort analysis of multicenter RCT Data from 1985 to 1989; number of sites not specified	Healthy women aged 18–40 years at least 42 days PP Exposed: BF women (n=1582) Unexposed: non-BF women (n=1161)	CuT 380A	Expulsion Removals for bleeding/pain Follow-up: 12 months	BF Expulsion rate at 12 mos Rate (95% CI) Rate of removal for bleeding/pain at 12 mos (95% CI Yes 3.6 (2.4-4.7) 3.2 (2.1-4.4) No 2.8 (1.9-3.7 5.5 (4.2-6.7) p-value 0.23 0.01	Long follow-up Large sample size Adequately defined exposure and outcome	Attrition rates not reported	II-2, good

BF, breastfeeding; FHI, Family health International; PID, pelvic inflammatory disease; PP, postpartum; SE, standard error; USAID, United States Agency of International Development.