GRADE table 1, [(Question 1): Among breastfeeding women...]. - Medical Eligibility Criteria for Contraceptive Use

GRADE table 1

(Question 1): Among breastfeeding women (and their infants), does the use of progestogen-only contraceptives (POCs) and levonorgestrel-releasing intrauterine devices (IUDs) have an impact on breastfeeding or infant health outcomes compared with those not using POCs? (Direct evidence)

Question 2: Among breastfeeding women (and their infants), does the use of progestogen-only contraceptives (POCs) and levonorgestrel-releasing intrauterine devices (LNG-IUDs) initiated up to 6 weeks postpartum have an impact on breastfeeding or infant health outcomes compared with initiation after 6 weeks postpartum? (Direct evidence)

Factor	Type and number of studies (number of participants)	Limitations	Inconsistency	Imprecision	Indirectness	Other factors	Quality	Estimate of effect
Progestogen-only pill (POP) vs combined oral contraceptive (COC) initiated at < 6 weeks postpartum
Breastfeeding continuation	1 RCT (n=127)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Low	Norethindrone vs ethinyl estradiol (EE) COC (1 RCT): 64% vs 64%, RR 0.99 (95% CI 0.76–1.3) at 8 weeks; 41% vs 44%, RR 0.94 (95% CI 0.63–1.4) at 6 months
Use of supplementation	1 RCT (n=127)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Low	Norethindrone vs EE COC (1 RCT): no difference at 8 weeks (data not provided)
Infant growth	1 RCT (n=127)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Low	Norethindrone vs EE COC (1 RCT): no difference in percent change in weight (P = 0.56), length (P = 0.41), or head circumference (P = 0.79) from weeks 2–8
LNG-IUD initiated at < 6 weeks postpartum vs non-hormonal contraception
Breastfeeding continuation	1 RCT (n=110)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Very low	LNG-UD (30 mcg/d or 10 mcg/d) vs Cu-IUD (1 RCT): 58% vs 79% at 8 months, RR 0.74 (95% CI 0.57–0.95)
Breastfeeding duration	1 RCT (n=110)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Very low	LNG-IUD 30 mcg/d vs LNG IUD 10 mcg/d vs Cu-IUD (1 RCT): 197 vs 182 vs 208 days (P > 0.05)
Infant growth	1 RCT (n=110)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	NA	Very low	LNG-IUD (30 mcg/d or 10 mcg/d) vs Cu-IUD (1 RCT): no differences through 12 months
Progestogen-only injectable initiated at < 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	3 cohort studies (n=617)	Very serious limitations (1 fair, 2 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	No clear differences in 2 studies; in a 3rd study weaning occurred later with DMPA or NET-EN
Use of supplementation	5 cohort studies (n=1370)	Very serious limitations (1 fair, 4 poor)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	All 5 studies found DMPA or NET-EN associated with similar or lower likelihood of exclusive breastfeeding
Duration of breastfeeding	5 cohort studies (n=1732)	Very serious limitations (1 fair, 4 poor)	No serious inconsistency	No serious imprecision	No indirectness	None	Low	All 5 studies found DMPA associated with no difference or increased duration of breastfeeding vs non-hormonal methods
Infant growth	6 cohort studies (n=4403)	Very serious limitations (5 poor)	No serious inconsistency	No serious imprecision	No indirectness	None	Low	None of 5 studies found DMPA or NET-EN associated with decreased infant growth; 1 study found progestogen-only injectable associated with increased weight gain through 3 months
POPs initiated at < 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	1 non-randomized trial (n=273) 3 cohort studies (n=756)	Serious limitations (1 fair-quality cohort study, 3 poor-quality studies)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	None of 4 studies found various POPs associated with lower likelihood of breastfeeding continuation; 2 studies found POPs associated with higher likelihood of breastfeeding continuation
Breastfeeding initiation	1 RCT (n=20) and 1 nonrandomized trial (n=20)	Very serious limitations (2 poor)	No serious inconsistency	Very serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	1 RCT found no difference between norethisterone at ≤ 14 hours postpartum (PP) vs placebo in breastfeeding initiation; 1 non-randomized trial found lynestrenol at 2 days PP associated with initiation of breastfeeding at 3 vs 5 days PP with placebo
Duration of breastfeeding	2 cohort studies (n=572)	Very serious limitations (2 poor)	No serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	2 studies found POPs associated with somewhat longer duration of breastfeeding vs non-hormonal comparators
Use of supplementation	2 cohort studies (n=1000)	Very serious limitations (1 fair, 1 poor)	Serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	1 fair-quality study found norgestrel associated with more frequent supplementary feeding but no difference in proportion of women supplementing; 1 poor-quality study found LNG associated with somewhat later initiation of supplementation (5.4 vs 4.6 months PP)
Infant growth	1 RCT (n=20), 1 non-randomized trial (n=20); 3 cohort studies (n=1083)	Serious limitations (2 fair-quality cohort studies, 3 poor-quality studies)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	4 studies found no difference on measures of infant growth; 1 small, poor-quality, non-randomized study found greater increase with lynestrenol than placebo
Progestogen-containing implants initiated at < 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	3 cohort studies (n=520)	Very serious limitations (1 fair, 2 poor)	Serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	3 studies reported conflicting findings regarding effects of progestogen-containing implants on measures of breastfeeding continuation; the 1 fair-quality study found no difference between nomegestrol implant in 2nd month PP vs Cu-IUD
Breastfeeding episodes	2 cohort studies (n=392)	Very serious limitations (1 fair, 1 poor)	No serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	2 studies found no differences in breastfeeding frequency
Duration of breastfeeding	1 cohort study (n=80)	Serious limitations (1 fair)	Cannot determine (1 study)	Very serious imprecision	No indirectness	None	Very low	1 fair-quality cohort study found no difference between etonogestrel (ETG) implant at 28–56 days PP vs Cu-IUD in duration of breastfeeding
Use of supplementation	3 cohort studies (n=430)	Very serious limitations (1 fair, 2 poor)	Serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	2 studies found no difference in use of supplementation; 1 study found norethindrone associated with increased likelihood of supplementation at 3 months
Infant growth	6 cohort studies (n=870)	Serious limitations (2 fair, 4 poor)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and assessment of outcomes^a	Low	2 fair-quality and 2 poor-quality studies found no difference in measures of infant growth; 1 poor-quality study found LNG associated with more weight gain than Cu-IUD; 1 poor-quality study found LNG associated with slower weight gain than Cu-IUD or barrier/no method
Multiple progestogen-only methods initiated at < 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	1 cohort study (n=319)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	1 study found no difference between LNG implant or POP prior to discharge vs non-hormonal contraception in breastfeeding continuation at 2–6 weeks PP
Use of supplementation	1 cohort study (n=319)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	1 study found no difference between LNG implant or POP prior to discharge vs non-hormonal contraception in use of supplementation at 2–6 weeks PP
Non-orally available progesterone initiated at < 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	2 cohort studies (n=1092)	Very serious limitations (1 fair, 1 poor)	Serious inconsistency	Serious imprecision	No indirectness	None	Very low	1 fair-quality study found progesterone pellets at 30–35 days PP associated with decreased likelihood of breastfeeding at 6 months (51% vs 58%) and 12 months (11% vs 18%); 1 poor-quality study found no difference between progesterone pellets at 30 or 60 days vs Cu-IUD or placebo injection in breastfeeding rates
Use of supplementation	2 cohort studies (n=1092)	Very serious limitations (1 fair, 1 poor)	No serious inconsistency	Serious imprecision	No indirectness	None	Very low	2 studies found no differences in use of supplementation
Infant growth	2 cohort studies (n=1092)	Very serious limitations (1 fair, 1 poor)	No serious inconsistency	Serious imprecision	No indirectness	None	Very low	2 studies found no differences in infant growth
LNG-IUD initiated at > 6 weeks postpartum vs non-hormonal
Duration of breastfeeding	1 RCT (n=320)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): 149 vs 160 days
Use of supplementation	1 RCT (n=320)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): no difference in exclusive breastfeeding
Infant growth	1 RCT (n=320)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): no difference in infant growth
Progestogen-only injectable initiated at > 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	1 RCT (n=170)	Very serious limitations (1 poor)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	DMPA at 6 weeks PP vs non-hormonal (1 RCT): no difference in rates of discontinuation
Duration of breastfeeding	1 cohort study (n=1538)	Serious limitations (1 fair)	Cannot determine (1 study)	No serious imprecision	No indirectness	None	Low	DMPA or NET-EN at 6–8 weeks PP vs non-hormonal contraception (1 cohort study): no difference in duration of breastfeeding
Use of supplementation	1 RCT (n=170); 1 cohort study (n=212)	Very serious limitations (2 poor)	No serious inconsistency	Serious imprecision	No indirectness	None	Very low	2 studies found no differences in use of supplementation
Infant growth	1 RCT (n=170); 2 cohort studies (n=1750)	Very serious limitations (1 fair-quality cohort study, 2 poor-quality studies)	No serious inconsistency	No serious imprecision	No indirectness	Variability in outcomes^a	Low	None of 3 studies found decreased infant growth with DMPA or NET-EN; 2 studies reported some findings suggesting greater weight gain
POP initiated at > 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	1 RCT (n=144)	Very serious limitations (1 poor)	Cannot determine (1 study)	Very serious imprecision	No indirectness	None	Very low	Norgestrel at 6 weeks PP vs non-hormonal contraception (1 RCT): no difference in discontinuation of breastfeeding
Duration of breastfeeding	2 cohort studies (n=1709)	Serious limitations (2 fair)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions^a	Low	2 studies found no difference in breastfeeding duration
Use of supplementation	1 RCT (n=144); 1 nonrandomized trial (n=120)	Very serious limitations (2 poor)	Serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	1 RCT found no difference in use of supplementation and 1 non-randomized trial found lower mean age at supplementation with lynestrenol vs IUD + placebo (11 vs 15 weeks, P not reported)
Infant growth	1 RCT (n=144); 3 nonrandomized studies (n=1829)	Serious limitations (2 fair-quality cohort studies, 2 poor-quality studies)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	4 studies found no difference in measures of infant growth
Progestogen-only implant or progestogen-containing IUD initiated at > 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	2 cohort studies (n=57)	Very serious limitations (2 poor)	No serious inconsistency	Very serious imprecision	No indirectness	None	Very low	2 studies found no difference in breastfeeding rates
Breastfeeding duration	4 cohort studies (n=2329)	Serious limitations (4 fair)	No serious inconsistency	No serious imprecision	No indirectness	Variability in outcomes^a	Low	4 studies found no difference in breastfeeding duration
Use of supplementation	3 cohort studies (n=549)	Serious limitations (2 fair, 1 poor)	No serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	3 studies found no difference in use of supplementation
Infant growth	6 cohort studies (n=2386)	Serious limitations (4 fair, 2 poor)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	6 studies found no difference in measures of infant growth
Multiple progestogen-only methods initiated at > 6 weeks postpartum vs non-hormonal
Breastfeeding duration	1 cohort study (n=34)	Very serious limitations (1 poor)	Cannot determine (1 study)	Very serious imprecision	No indirectness	None	Very low	DMPA, POP or LNG-IUD vs non-hormonal contraception (1 cohort study): 183 vs 183 days (P =0.38)
Infant growth	1 cohort study (n=140)	Very serious limitations (1 poor)	Cannot determine (1 study)	Very serious imprecision	No indirectness	None	Very low	DMPA at 6 weeks PP vs non-hormonal contraception (1 cohort study): no difference in weight through 26 weeks PP
Non-orally available progesterone initiated at > 6 weeks postpartum vs non-hormonal
Breastfeeding continuation	2 cohort studies (n=788)	Very serious limitations (1 fair, 1 poor)	No serious inconsistency	No serious imprecision	No indirectness	Variability in interventions^a	Very low	1 fair-quality study found elcometrine implant associated with higher breastfeeding rate at 3 and 5 months (but not at 9 and 12 months); 1 poor-quality study found no difference between progesterone pellets vs Cu-IUD or placebo at 6 or 13 months PP
Breastfeeding duration	1 cohort study (n=200)	Serious limitations (1 fair)	Cannot determine (1 study)	Serious imprecision	No indirectness	None	Very low	Nesterone implant at 55–60 days PP vs Cu-IUD (1 cohort study): 273 vs 263 days (NS)
Infant growth	3 cohort studies (n=988)	Serious limitations (2 fair, 1 poor)	No serious inconsistency	No serious imprecision	No indirectness	Variabilty in interventions and outcomes^a	Low	3 studies found no differences in measures of infant growth
Earlier vs later initiation of progestogen-only methods
Breastfeeding continuation	2 RCTs (n=165) and 1 cohort study (n=35)	Serious limitations (2 fair-quality RCTs, 1 poor-quality cohort study)	No serious inconsistency	Serious imprecision	No indirectness	Variabilty in interventions and outcomes^a	Low	1 RCT found immediate LNG-IUD associated with lower breastfeeding rate at 6 months vs initiation at 6–8 weeks PP (6% vs 24%, P = 0.02); 1 cohort study found norethindrone implant at 6 days PP associated with lower rate at 8 months (57% vs 67%); 1 RCT found no difference in rate of lactation failure
Breastfeeding duration	1 RCT (n=96)	Serious limitations (1 fair)	Not applicable 1 study)	Very serious imprecision	No indirectness	None	Very low	Immediate LNG-IUD vs 6–8 weeks PP (1 RCT): 5 vs 8.5 weeks (P=0.06)
Use of supplementation	3 RCTs (n=205) and 4 cohort studies (n=660)	Serious limitations (3 fair-quality RCTs, 1 fair- and 3 poor-quality cohort studies)	Serious inconsistency	No serious imprecision	No indirectness	Variability in interventions and outcomes^a	Very low	Inconsistent effects on use of supplementation among 7 studies
Infant growth	1 RCT (n=40) and 3 cohort studies (n=543)	Very serious limitations (1 fair-quality RCT, 3 poor-quality cohort studies)	No serious inconsistency	Serious imprecision	No indirectness	Variability in interventions and outcomes^a	Low	4 studies found no differences in measures of infant growth

: CI: confidence interval; COC: combined oral contraceptive; Cu-IUD: copper-bearing intrauterine device; EE: ethinyl estradiol; LNG-IUD: levonorgestrel intrauterine device; NA: not applicable; NS: not significant; POP: progestogen-only pill; PP: postpartum; RCT: randomized controlled trial; RR: relative risk.
a: Refers to variability in the progestogen evaluated, timing of initiation of POC, outcome measures assessed, and/or timing of outcome assessment.

From: I, Development of the Medical eligibility criteria for contraceptive use, fifth edition

Cover of Medical Eligibility Criteria for Contraceptive Use

Medical Eligibility Criteria for Contraceptive Use. 5th edition.

Geneva: World Health Organization; 2015.

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