Contracepción hormonal combinada versus no hormonal versus con progestina solamente durante la lactancia
Resumen
Antecedentes
La anticoncepción posparto mejora la salud de las madres y los niños al alargar los intervalos entre los partos. En el caso de las mujeres que lactan, las opciones anticonceptivas se ven limitadas por la preocupación por los efectos hormonales sobre la calidad y cantidad de la leche y el paso de las hormonas al lactante. Lo ideal es que el anticonceptivo elegido no interfiera con la lactancia o el crecimiento del lactante. El momento en el que se inicia la anticoncepción también es importante. Inmediatamente después del parto, la mayoría de las mujeres tienen contacto con un profesional de la salud, pero muchas no regresan para recibir consejería anticonceptiva de seguimiento. Sin embargo, la iniciación inmediata de los métodos hormonales puede interrumpir el inicio de la producción de leche.
Objetivos
Determinar los efectos de los anticonceptivos hormonales sobre la lactancia y el crecimiento infantil
Métodos de búsqueda
Se realizaron búsquedas de ensayos elegibles hasta el 2 de marzo de 2015. Las fuentes incluyeron el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov y la ICTRP. Se examinaron los artículos de revisión y se estableció contacto con los investigadores.
Criterios de selección
Se buscaron los ensayos controlados aleatorizados en cualquier idioma que compararon la anticoncepción hormonal versus otra forma de anticoncepción hormonal, anticoncepción no hormonal o placebo durante la lactancia. La anticoncepción hormonal incluye anticonceptivos orales combinados o que solo contienen progestina, anticonceptivos inyectables, implantes y dispositivos intrauterinos.
Los ensayos debían tener una de las medidas de resultado primarias: cantidad o composición bioquímica de la leche materna; inicio, mantenimiento o duración de la lactancia; crecimiento infantil; o momento del inicio de la anticoncepción y efecto sobre la lactancia. Las medidas de resultado secundarias incluyeron la eficacia anticonceptiva durante la lactancia materna y el intervalo del parto.
Obtención y análisis de los datos
Para las variables continuas se calculó la diferencia de medias (DM) con el intervalo de confianza (IC) del 95%. Para los resultados dicotómicos se calculó el odds ratio (OR) de Mantel‐Haenszel con el IC del 95%. Debido a las diferencias en las intervenciones y las medidas de resultado no se realizó un metanálisis.
Resultados principales
En 2014 se agregaron siete ensayos para un nuevo total de 11. Antes de 1985 se publicaron cinco informes, y seis entre 2005 y 2014. Estos estudios incluyeron 1482 mujeres. Cuatro ensayos examinaron los anticonceptivos orales combinados (AOC) y tres estudiaron un sistema intrauterino liberador de levonorgestrel (SIU‐LNG). Se encontraron dos ensayos de píldoras con progestina sola (AOPS) y dos de implante liberador de etonogestrel. Los estudios más antiguos a menudo carecieron de resultados cuantificados. La mayoría de los ensayos no informaron diferencias significativas entre los brazos del estudio en cuanto a la duración de la lactancia materna, la composición de la leche materna o el crecimiento del lactante. Se observaron excepciones, principalmente en los estudios más antiguos con información limitada.
Para la duración de la lactancia materna, dos de ocho ensayos indicaron un efecto negativo sobre la lactancia. Un estudio de AOC informó de un efecto negativo sobre la duración de la lactancia en comparación con placebo, pero no cuantificó los resultados. Otro ensayo mostró un porcentaje más bajo de lactancia materna en el grupo con SIU‐LNG a los 75 días versus el grupo con DIU no hormonal (p informada < 0,05), pero no hubo diferencias significativas al año.
Para el volumen de leche materna, dos estudios más antiguos indicaron un menor volumen para el grupo AOC versus el grupo placebo. Un ensayo no cuantificó los resultados. El otro mostró medias más bajas (ml) para el grupo AOC, p.ej. a las 16 semanas (DM ‐24,00; IC del 95%: ‐34,53 a ‐13,47) y a las 24 semanas (DM ‐24,90; IC del 95%: ‐36,01 a ‐13,79). Otros cuatro ensayos no informaron diferencias significativas entre los grupos de estudio en cuanto al volumen o la composición de la leche con dos AOPS, un AOC o el implante de etonogestrel.
Siete ensayos estudiaron el crecimiento infantil; uno mostró un mayor aumento de peso (gramos) para el implante de etonogestrel versus ningún método durante seis semanas (DM 426,00; IC del 95%: 58,94 a 793,06), pero menos comparado con el acetato de medroxiprogesterona de depósito (AMPD) de seis a 12 semanas (DM ‐271,00; IC del 95%: ‐355,10 a ‐186,90). Los otros estudiaron AOPS, AOC versus AOPS, o un SIU‐LNG.
Conclusiones de los autores
Los resultados no fueron consistentes entre los 11 ensayos. La evidencia fue limitada para cualquier método hormonal en particular. La calidad de la evidencia fue moderada en general y baja para tres de los cuatro ensayos controlados con placebo de AOC o AOPS. Un análisis de sensibilidad incluyó estudios con evidencia de calidad moderada o alta y datos de resultado suficientes. Cinco ensayos no indicaron diferencias significativas entre los grupos en cuanto a la duración de la lactancia materna (tiempos de inserción del implante de etonogestrel, AOC versus AOPS y SIU‐LNG). Para el volumen o la composición de la leche materna, un estudio de AOC mostró un efecto negativo, mientras que un ensayo de implantes no mostró diferencias significativas. De los cuatro ensayos que evaluaron el crecimiento infantil, tres no indicaron diferencias significativas entre los grupos. Uno mostró un mayor aumento de peso en el grupo de implante de etonogestrel versus ningún método, pero menos versus el AMPD.
PICO
Resumen en términos sencillos
Control de la natalidad hormonal y no hormonal durante la lactancia materna
El control de la natalidad para las mujeres que lactan es importante en todo el mundo. Retrasar el siguiente embarazo mejora la salud de las mujeres y los niños. Cada año millones de mujeres deciden si usan anticonceptivos después de tener un recién nacido. La decisión incluye el tipo de método anticonceptivo y cuándo comenzar a utilizarlo. Este es un tema de debate entre los investigadores y los proveedores de atención médica. A algunos les preocupa que las hormonas puedan afectar la leche materna y, por lo tanto, el crecimiento del lactante. Idealmente, el control de la natalidad no afectaría el tipo ni la cantidad de leche materna, ni el crecimiento del lactante. También es importante identificar el mejor momento para comenzar a utilizar los métodos anticonceptivos. Cuando el retorno de los ciclos mensuales no está claro la mujer podría quedar embarazada de nuevo.
Los métodos combinados para el control de la natalidad contienen las hormonas estrógeno y progestina. Otros tipos de anticonceptivos solo contienen progestina o no contienen hormonas. Se analizó si los métodos anticonceptivos combinados o los métodos que solo contienen progestina afectan la lactancia materna más que otros métodos. Se realizaron búsquedas electrónicas de ensayos aleatorizados de anticonceptivos utilizados durante la lactancia materna, hasta el 2 de marzo de 2015. Estos ensayos compararon los métodos hormonales con otros métodos hormonales o con placebo (método "simulado"). También se examinaron las listas de referencias para encontrar ensayos. En la revisión inicial también se le escribió a los investigadores para encontrar otros ensayos.
Se incluyeron 11 estudios con un total de 1482 mujeres. Estos ensayos examinaron muchos métodos: píldoras, un implante, "Depo" inyectable y un dispositivo intrauterino (DIU) hormonal. Algunos informes más antiguos no tenían muchos datos. La mayoría de los ensayos no mostraron diferencias importantes debido al uso de anticonceptivos hormonales. Dos de los ocho ensayos observaron menos lactancia materna entre las mujeres que utilizaron anticonceptivos hormonales. Uno fue una píldora combinada con pocos resultados y el otra un DIU hormonal. En un estudio los lactantes del grupo con implantes aumentaron más de peso que los del grupo con ningún método, pero menos que los del grupo "Depo". Dos ensayos observaron que una píldora combinada tuvo un efecto negativo sobre el volumen o el contenido de la leche materna. Un informe no tenía muchos datos. El otro mostró un volumen más bajo para las usuarias de píldoras combinadas en comparación con las mujeres que tomaban píldoras con progestina solamente.
Se encontró poca información sobre cualquier método anticonceptivo específico, con generalmente dos estudios por método. Los resultados no fueron consistentes entre los ensayos. En general los ensayos fueron de calidad moderada. Los resultados de una mejor calidad mostraron poco efecto sobre la lactancia materna o el crecimiento del lactante.
Authors' conclusions
Background
Description of the condition
Contraception for women who are breastfeeding is a public health issue of global importance. According to early Demographic and Health Surveys (DHS), nearly two‐thirds of women in their first postpartum year have an unmet need for family planning (WHO 2013). More recent DHS indicate that unmet need for modern contraceptive methods is 32% among married women in general, and one‐third to one‐half of unmarried women have an unmet need for such methods (Westhoff 2012). Each year more than 100 million women make decisions about beginning or resuming contraception after childbirth (Tsui 1997). These decisions include the choice of contraceptive method and the time at which to begin use. For women who are breastfeeding, the choice and timing of hormonal contraception may influence both lactation and infant growth.
Breastfeeding has well‐established health benefits. It provides the infant with complete nutrition up to six months, a safe food source, and immunological defense against infectious diseases (USAID 2009; AAP 2012). Breastfeeding has economic benefits from conserving funds that would be spent on milk substitutes (AAP 2012). Lactation is associated with reducing a woman's risk of type 2 diabetes and ovarian and breast cancer (Ip 2007). Infants exclusively breastfed for the first six months appear to have better health outcomes than those partially breastfed as of three or four months of age (Kramer 2012).
Breastfeeding influences the need for and timing of postpartum contraception. An interval of anovulation occurs after delivery, and the length of time until ovulation resumes depends on breastfeeding patterns, biological variation, nutrition, geography, culture, and socioeconomic factors (Knijff 2000). Lactation itself can be an effective form of temporary contraception, known as the lactational amenorrhea method (LAM) (Van der Wijden 2003). For LAM to be effective, the woman must fully (or nearly fully) breastfeed, have no menstrual bleeding, and be within six months of delivery (Kennedy 2011; K4 Health 2014). Return of menstruation and ovulation can be unpredictable in breastfeeding women. Therefore, the timing of contraception initiation is important. Ideally, the contraceptive method chosen should not interfere with lactation.
Description of the intervention
Contraception after childbirth improves the health of mothers and infants by lengthening birth intervals. Women are more likely to report births or pregnancies as unintended when they occur within an interval of 24 months or less (Tsui 1997). Preventing such unintended pregnancies reduces health risks and helps avoid associated financial and psychological costs. A longer birth interval of 18 to 27 months decreases the risk of major maternal complications including death, third‐trimester bleeding, puerperal endometritis, and anemia (Conde‐Agudelo 2000; WHO 2005). To reduce risk for poor maternal and infant health outcomes, the World Health Organization has recommended waiting 24 months before attempting the next pregnancy (WHO 2005).
Hormonal contraception includes combined methods that contain both estrogen and progestin as well as progestin‐only methods. Combined hormonal contraceptives include combined oral contraceptives (COCs), combined injectables, and the combined vaginal ring and transdermal patch. Progestin‐only methods include progestin‐only pills (POPs), the injectable depot medroxyprogesterone acetate (DMPA), levonorgestrel and etonogestrel implants, and the levonorgestrel intrauterine system. A progesterone vaginal ring was developed for use during lactation and is available in some Latin American countries (RamaRao 2013).
How the intervention might work
Hormonal contraceptives, especially those containing estrogen, may impair lactation through their effect on prolactin, the hormone responsible for production of milk. During pregnancy, prolactin levels rise and they peak at delivery. However, during pregnancy, both estrogen and progesterone block the effect of prolactin on the breasts. After delivery, levels of both estrogen and progesterone drop markedly, and, without their inhibitory effects, prolactin initiates milk production. Infant suckling stimulates more prolactin, which then sustains milk production. Breast engorgement and full milk secretion start three to four days after delivery, when estrogen and progesterone have sufficiently cleared from the maternal circulation (Speroff 2004; Pang 2007).
Choices of contraception may be limited for lactating women because of concerns about potential negative hormonal effects on quality and quantity of milk, passage of hormones to the infant, and infant growth and development. Some studies have found negative effects on lactation from COCs but not from progestin‐only contraception (Kapp 2010a; Kapp 2010b; Kennedy 2011). However, those studies had various ways of measuring effects on milk production, yielded inconsistent results, and generally did not show negative effects on infants. Theoretical concerns about milk production focus on the early postpartum period, i.e. the onset of lactogenesis (CDC 2011; Gurtcheff 2011). Gonadal steroids may also impact milk supply in established lactation, as suggested by evidence of slower growth among children who continue to breastfeed when their mothers conceive another pregnancy (Bohler 1996). To determine whether hormonal contraception affects milk production, studies ideally would quantify the rate of exclusive or full breastfeeding, as well as the supplementation that infants receive, among women using different contraceptive methods. In the setting of mixed feeding, comparisons of infant growth are difficult to interpret because mothers can compensate for differences in milk supply by formula supplementation.
Due to concerns about the effect on lactation, combined hormonal contraceptives are considered category 4 for breastfeeding women up to six weeks postpartum and category 3 for six weeks to six months (WHO 2009; CDC 2011). Category 3 means that the theoretical or proven risks usually outweigh the advantages of using the method. The method is not usually recommended unless more appropriate methods are unavailable or unacceptable (WHO 2009). Most progestin‐only methods are considered category 3 for less than six weeks postpartum (WHO 2009). For the first month postpartum in the United States, they are considered category 2, i.e. the advantages of using the method generally outweigh the risks (CDC 2011).
Why it is important to do this review
Despite potential adverse effects of COCs on lactation, many women prefer this method (Erwin 1994). Combined oral contraceptives have many benefits, including familiarity with the method, effectiveness, safety, reversibility, excellent cycle control, a decrease in menstrual cramps and pain, decreased days of bleeding and amount of blood loss, and other noncontraceptive benefits. Other hormonal methods, including the progestin‐only pill, may not offer all of these advantages (Raymond 2011). Progestin‐only pill use is estimated at only 0.4% in the United States, according to an analysis of data from the National Survey of Family Growth (Hall 2012). The percentage may be much higher for breastfeeding women, but the sample size was very small for postpartum women. Some women quit breastfeeding early so they can start the COC (Erwin 1994).
Examining the impact of long‐acting reversible contraception (LARC) on lactation is also important. The levonorgestrel‐releasing intrauterine system (LNG‐IUS) and the etonogestrel‐releasing implant (ETG implant) provide highly effective birth control; both are progesterone‐only methods.
Clinical recommendations must be evidence‐based if women are to make informed choices concerning contraception while breastfeeding. This updated review examined the effects of combined hormonal contraceptives and progestin‐only contraceptives on lactation and infant growth.
Objectives
To determine the effects of hormonal contraceptives on lactation and infant growth
Methods
Criteria for considering studies for this review
Types of studies
All randomized controlled trials (RCTs) reported in any language that compared hormonal contraception during lactation versus other hormonal contraception, nonhormonal contraception, or placebo.
Types of participants
Breastfeeding women of any age or parity who desired contraception
Types of interventions
Any form of hormonal contraception compared with another form of hormonal contraception, nonhormonal contraception, or placebo. Combined hormonal contraceptives include oral or injectable methods, vaginal rings and transdermal patches. Progestin‐only contraceptives include oral and injectable methods, subdermal implants, and hormonal intrauterine devices.
Types of outcome measures
For the 2015 update, we separated the original list of outcomes into primary and secondary outcomes. Trials must have reported on at least one of the primary outcomes, which focus on the effect of the hormonal contraceptive on lactation.
Primary outcomes
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Quantity of milk
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Biochemical analysis of milk composition
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Initiation, maintenance and duration of lactation (any or fully breastfeeding)
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Infant growth
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Timing of contraception initiation and its effects on lactation
Secondary outcomes
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Efficacy of contraceptive method while breastfeeding (pregnancy)
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Birth interval
Search methods for identification of studies
Electronic searches
We searched for eligible RCTs until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, and LILACS. We also searched for recent trials via ClinicalTrials.gov and the search portal of the International Clinical Trials Registry Platform (ICTRP). Search strategies are shown in Appendix 1. The initial review and the 2005 and 2008 updates also included EMBASE (Appendix 2).
Searching other resources
For the initial review, we began with review articles. We also examined reference lists of relevant articles and book chapters to seek publications comparing different forms of contraception in breastfeeding women and their effects on lactation. We contacted other investigators in the field to find publications that might have been missed, including unpublished reports. For the 2015 update, we also examined reference lists of reviews and relevant articles for other trials.
Data collection and analysis
2003: For the initial review, the authors read titles and abstracts from the searches to assess whether trials appeared to meet the inclusion criteria. We retrieved the full text when necessary. The authors verified that included references were satisfactory and reviewed others that could have met the inclusion criteria. They resolved disagreements by consensus. They sought additional information from investigators of the original included trials. Two investigators responded to questions about randomization methods and blinding (Miller 1970; WHO 1984).
2005 to 2010: The authors reviewed titles and abstracts from the database searches to determine whether trials appeared to be eligible. We retrieved the full text when necessary to determine whether the trial met the inclusion criteria.
2014: We describe below the data collection and analysis methods used in the current version of this review.
Selection of studies
We assessed for inclusion all titles and abstracts identified during the literature searches with no language limitation.
Data extraction and management
Two authors independently abstracted the data. One author entered the data into Review Manager (RevMan 2014), and a second author verified the accuracy. We resolved discrepancies through discussion. In Characteristics of included studies, we focused on primary and secondary outcomes for this review, which may not include all outcomes from each study.
Assessment of risk of bias in included studies
We examined studies for methodological quality, according to recommended principles (Higgins 2011). We considered factors such as study design, methods used to generate the randomization sequence, allocation concealment, blinding, and losses to follow‐up and to early discontinuation. We also examined the methods used for outcome assessment.
Measures of treatment effect
For continuous variables, we computed the mean difference (MD) with 95% confidence interval (CI) using a fixed‐effect model. RevMan uses the inverse variance approach. For dichotomous outcomes, we calculated the Mantel‐Haenszel odds ratio (OR) with 95% CI using a fixed‐effect model. When multivariate analysis was conducted, we presented the results as reported by the trial investigators.
Dealing with missing data
We wrote to investigators to request missing data, such as sample sizes for analysis and actual numbers for outcomes presented in figures. However, we limited our requests to studies less than 10 years old, unless a report was produced within the past five years. Investigators are unlikely to have access to data from 10 years ago.
Data synthesis
To assess evidence quality and to address confidence in the effect estimates, we applied principles from GRADE (Grades of Recommendation, Assessment, Development and Evaluation) (Balshem 2011; Higgins 2011). When meta‐analysis is not viable because of varied interventions, a Summary of findings table is not feasible. In this review, experimental and comparison interventions differed across the included trials. Outcomes assessed also varied, e.g. breast milk composition, reports of breastfeeding, or change in infant weight. Because of the heterogeneity of interventions and outcomes, we did not conduct a formal GRADE assessment with an evidence profile and Summary of findings table (Guyatt 2011).
Our quality assessment was based on the quality of evidence from the individual studies, which could be rated as high, moderate, low, or very low. We considered the evidence from RCTs to be of high quality initially, then downgraded it for each of the following: (1) no information on randomization sequence generation or allocation concealment, or one was clearly inadequate; (2) no blinding; (3) follow‐up less than 8 weeks for infant growth or less than 12 weeks for breastfeeding; (4) losses greater than 20%; and (5) information missing on both blinding and losses.
Sensitivity analysis
We examined a subgroup of trials that provided evidence of moderate or high quality and reported sufficient outcome data. Most of the older trials did not quantify results, limiting the interpretation of effect. Even recent trials might not have reported sufficient detail for interpreting the outcome data presented.
Results
Description of studies
Results of the search
The initial search in 2003 identified 50 articles as potentially eligible for inclusion. Seven were included and 43 were excluded, as indicated below. Searches in 2005, 2008, and 2010 did not yield any eligible studies.
In 2014, we identified a study that was eligible but was not include earlier. Therefore, we ran searches starting from September 2001. This revised search, completed in 2015, produced 215 unduplicated references (Figure 1). Duplicates removed totaled 109 (93 identified electronically and 16 by hand). With four citations identified from other sources, we had 219 unduplicated references. We reviewed the full text of 14 items (9 primary and 5 secondary). From recent clinical trial listings, we obtained 15 unduplicated trials. We located a conference abstract for a completed trial, which we included, and we listed another trial in Ongoing studies. In this review, we included seven new primary reports plus two secondary articles. We excluded two new primary reports plus one secondary article. We also discarded two more secondary articles related to an included trial; the abstracts indicated they did not meet our criteria.
Study flow diagram (2014).
Included studies
A total of 11 trials met our inclusion criteria. The seven trials added in 2014 included three recent reports (Gurtcheff 2011; Espey 2012; Dutta 2013), a recent abstract (Stuart 2014), and three older reports missed during earlier searches (Heikkilä 1982; Shaamash 2005; Brito 2009).
The 11 trials included a total of 1482 women. Sample sizes ranged from 20 to 320 with a median of 80. Only four provided information on sample size calculations. Outcomes of focus were breastfeeding (Shaamash 2005; Gurtcheff 2011; Espey 2012) and infant growth (Shaamash 2005); one was designed to assess change in the woman's weight (Brito 2009).
Contraceptive methods examined
Seven trials studied just progestin‐only methods.
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Two compared progestin‐only pills (POPs) versus placebo (Giner Velazquez 1976; Dutta 2013).
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Three studied a progestin‐only intrauterine systems (IUS); two compared a hormonal IUS versus a nonhormonal IUD (Heikkilä 1982; Shaamash 2005), and one examined different insertion times for the same hormonal IUS (Stuart 2014).
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Two focused on a progestin‐only implant; one compared the implant versus no contraceptive for the first six weeks followed by a progestin‐only injectable (Brito 2009), and the other examined different insertion times for the same implant (Gurtcheff 2011).
Four trials examined COCs.
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Two studied a COC versus placebo (Semm 1966; Miller 1970).
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Two compared a COC versus a POP (WHO 1984; Espey 2012).
Outcomes assessed
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For breast milk, two studies examined quantity (Semm 1966; Miller 1970) and four reported on quantity and composition (Giner Velazquez 1976; WHO 1984; Gurtcheff 2011; Dutta 2013).
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Seven trials assessed any or full (exclusive) breastfeeding (Miller 1970; Heikkilä 1982; Shaamash 2005; Brito 2009; Gurtcheff 2011; Espey 2012; Stuart 2014).
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Seven studies reported infant growth (Giner Velazquez 1976; Heikkilä 1982; WHO 1984; Shaamash 2005; Brito 2009; Espey 2012; Dutta 2013).
Excluded studies
The initial review excluded 43 reports. Currently, we list articles as 'excluded' if the full text was needed to determine eligibility; otherwise, we 'discard' the abstract. Of the original 43 studies, 14 did not require full‐text review. We removed those 14 studies from 'excluded' to shorten the list, and listed them for reference in this update (Appendix 3). Most of the remaining articles had been excluded because communication with investigators indicated the trials were not RCTs, or because the method of participant allocation was unclear. In addition, Drury 1986 and Gellen 1984 were subgroup analyses that examined similar outcomes from WHO 1984 and were dropped from consideration.
In 2014, we divided the outcomes into primary and secondary and required one of the primary outcome measures. An earlier included trial was no longer eligible (Were 1997). The study had no outcomes addressing lactation; no pregnancy occurred in either group. We excluded three additional trials (Rodrigues da Cunha 2001; Chen 2011; Shaaban 2013) for design issues or for lack of our primary outcomes (Characteristics of excluded studies).
Risk of bias in included studies
The included trials span a publication period of nearly 50 years; earlier reports typically have more reporting limitations than later ones. The quality of evidence is discussed below and is summarized later (Table 1). In addition, Figure 2 presents the risk of bias for each study, and Figure 3 summarizes the risk of bias for all included trials.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Four of the recent trials mentioned some type of computer‐generated sequence (Shaamash 2005; Brito 2009; Gurtcheff 2011; Espey 2012), as did one earlier report (WHO 1984). Four of the five early trials and a recent preliminary report did not specify the method used to generate the random sequence (Semm 1966; Miller 1970; Giner Velazquez 1976; Heikkilä 1982; Dutta 2013). Additionally, Miller 1970 stratified the 'randomization' by gender of the infant and showed a disparity in baseline characteristics (primiparas) unlikely to result from a random process. Heikkilä 1982 also appeared to have an imbalance by parity, but the difference reportedly was not significant.
Allocation
Reporting of allocation concealment varied. One trial used pharmacy‐blinded pill packages (Espey 2012). Two used sealed, sequentially numbered, opaque envelopes (Shaamash 2005; Gurtcheff 2011). We determined through communication with an investigator that another also used sealed, opaque envelopes (WHO 1984). The remaining trials did not report the method of allocation concealment.
Blinding
Four trials of oral contraceptives (OCs) had placebos; two used identically labeled placebos (Semm 1966; Miller 1970). Miller 1970 and Giner Velazquez 1976 mentioned double‐blinding but did not describe the specifics. Written communication from Miller 1970 indicated that participants and clinicians were kept unaware of participant treatment assignments. Dutta 2013 did not mention blinding.
Two trials compared combined and progestin‐only oral contraceptives. Espey 2012 used pharmacy‐blinded pill packages. Written correspondence from an investigator in WHO 1984 (Tankeyoon) indicated that participants and clinicians were kept unaware of treatment assignments.
The two implant studies were not blinded. Brito 2009 was identified as an open trial of different contraceptive methods. Gurtcheff 2011 noted that blinding was not feasible because implants were inserted at different time points.
Of the three LNG‐IUS studies, Heikkilä 1982 noted that participants were unaware of which IUD was inserted, Stuart 2014 was listed as open label, and Shaamash 2005 did not mention blinding.
Incomplete outcome data
Four trials did not mention any losses to follow‐up, exclusions, or discontinuations (Semm 1966; Giner Velazquez 1976; Shaamash 2005; Dutta 2013). Heikkilä 1982 had no loss to follow‐up. Three trials had losses less than 20% (Miller 1970; Brito 2009; Gurtcheff 2011).
Losses were greater than 20% in two trials (WHO 1984; Espey 2012). In WHO 1984, the disposition of participants in the randomized arms was unclear. One table indicated that 50 participants in each arm completed the study, yet tables with outcome data showed data for 57 and 58 participants in the study arms at 24 weeks (trial completion) (WHO 1984). Losses at 16 weeks were 22% for the COC group and 14% for the POP group. At 24 weeks, from 32% to 34% of participants in each randomized arm were not included in the analysis. The investigators stated that participants who discontinued or were lost to follow‐up were analyzed via noncompeting risk life‐table procedures, and at least one participant was excluded after randomization.
Effects of interventions
Progestin‐only pills (POPs) versus placebo
These two studies did not provide sufficient data for analysis. The older trial did not provide actual values for the outcomes and the newer trial report did not have sample sizes for analysis or information on losses. Both studies noted no significant differences between the study groups in breast milk volume and composition and in infant growth.
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Giner Velazquez 1976 (n = 20) compared a POP containing norethindrone 350 μg versus a placebo for 14 days, starting 48 hours postpartum. Results were presented in figures without actual numbers. The investigators reported no significant differences between the study groups in milk volume and composition, nor in infant growth.
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In Dutta 2013 (n = 400), a POP containing desogestrel 75 μg was compared with placebo, starting six weeks postpartum. This 'preliminary report' stated the intervention was provided for six months. Results were presented in tables without time frames for assessments or specific sample sizes for analysis. The groups were not significantly different for amount or composition of breast milk nor for percent of infants with 'normal growth' (weight, length, and head circumference) (reported P > 0.15). Pregnancy was 0.5% in the POP group and 4% for the placebo group (reported P = 0.018).
Progestin‐only IUS versus nonhormonal IUD or different insertion times
Two studies compared a levonorgestrel‐releasing intrauterine system (LNG‐IUS) versus a nonhormonal intrauterine device (IUD). Neither provided sample sizes for analysis; results are presented as reported by the investigators.
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Heikkilä 1982 (n = 80) compared an LNG‐IUS (30 μg) versus the Nova T IUD. Insertion was done at six weeks postpartum with a range from 29 to 56 days. Sample sizes were lacking in most tables.
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The source of breastfeeding data was unclear (record or recall); one analysis date (75 days after insertion) did not correspond to clinic visit times (3, 6, and 12 months after insertion). The investigators did not mention whether women were asked to record days of breastfeeding as they did for bleeding and spotting. The percentage of women breastfeeding at 75 days was lower in the LNG‐IUS group than in the Nova T group (Analysis 1.1). However, the groups did not differ significantly in mean days of breastfeeding during the study (Analysis 1.2).
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Women were asked to have their infants weighed and measured monthly and to record those numbers on a special card; results were shown in figures without actual numbers. Reportedly, infant growth did not differ between the two study groups.
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A secondary article noted that no pregnancies occurred during the study.
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Shaamash 2005 (n = 320) compared the LNG‐IUS (20 μg) versus the CuT 308A IUD. The article did not provide sample sizes for analysis or information on losses. Means and standard deviations (SDs) or standard errors (SEs) are presented as available for the 6‐ and 12‐month assessments. The groups did not differ significantly for mean infant weight or length or in the Kaplan‐Meier rates for full breastfeeding or continued use of the IUS or IUD (Analysis 2.1 to Analysis 2.4). Sample size for the study was based on detecting differences in breastfeeding rate and infant weight gain. No pregnancy occurred in either group.
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In Stuart 2014 (n = 35), the LNG‐IUS was inserted either within 48 hours of delivery or four to eight weeks after delivery. The trial was stopped early because expulsion rates met a priori stopping rules. Only 35 women were randomized; 190 had been planned. At the six‐month study visit, the groups were not significantly different for any breastfeeding, but the sample size was much smaller than was intended (Analysis 3.1).
Progestin‐only implant versus no method or delayed method
Two studies examined the etonogestrel‐releasing (ETG) implant. Brito 2009 compared the implant versus no contraceptive for the first six weeks, then DMPA initiated at postpartum week six. In Gurtcheff 2011, both groups received the ETG implant, either by early insertion (one to three days postpartum) or standard insertion (four to eight weeks postpartum).
-
In Brito 2009 (n = 40), the sample size calculation was based on the women's weight change and a metabolic measure, which are not outcomes for our review. Women with a body mass index ≥ 30 kg/m2 were excluded from the trial, potentially affecting generalizability. The study groups did not differ significantly in proportions of women fully breastfeeding at 6 or 12 weeks postpartum (Analysis 4.1). None of the participants completely ceased breastfeeding during the study. Those who were not fully breastfeeding had started supplemental feeding. For infant weight, mean change (grams) by six weeks was greater in the ETG implant group than in the no‐contraceptive group (MD 426.00, 95% CI 58.94 to 793.06; Analysis 4.2). The wide CI indicates imprecision in the estimate; the standard deviations were large. Mean change between 6 and 12 weeks was lower for the ETG implant group than for the group that received DMPA (MD ‐271.00, 95% CI ‐355.10 to ‐186.90; Analysis 4.2). The report did not provide the actual infant weights.
-
For Gurtcheff 2011 (n = 69), the main outcomes were lactation failure and time to lactogenesis stage II (copious milk secretion). Sample size was based on establishing non‐inferiority in those outcomes. Non‐inferiority margins were a 15% increase in lactation failure and an additional eight hours to lactogenesis II in the early insertion group, as assessed through the 95% CI. Study groups were not significantly different for lactation failure (Analysis 6.1), mean time to lactogenesis (Analysis 6.2), or mean creamatocrit of breast milk at six weeks (Analysis 6.3). See Characteristics of included studies for explanations of these outcomes. However, our results differed from the non‐inferiority results for time to lactogenesis; our 95% CI exceeded the prespecified margin of an additional eight hours (MD ‐0.90, 95% CI ‐9.90 to 8.10). For breastfeeding (full or any), the investigator provided the actual numbers for analysis. Early and standard insertion groups did not differ significantly for full breastfeeding (Analysis 6.4) or for any breastfeeding (Analysis 6.5) at any time point. About half of study participants were fully breastfeeding at two weeks.
Combined oral contraceptive versus placebo
Findings from Miller 1970 and Semm 1966 were conflicting. Results were presented in figures without actual numbers. Neither trial quantified the outcomes, making interpretation difficult.
-
Miller 1970 (n = 50) examined a COC containing norethindrone 1 mg plus mestranol 80 μg versus placebo. The investigators noted inhibitory effects on milk volume and lactation duration from COC use. They indirectly measured milk volume by assessing the subjective need for supplemental infant feeds and infant weight as a proxy for milk adequacy. Only general estimates were given for the effects of the COC on lactation duration.
-
Semm 1966 (n = 100) compared a COC containing lynestrenol 2.5 mg plus mestranol 75 μg versus placebo. The investigators found no differences in milk volume or lactation initiation during the first 10 days postpartum. Hormone doses were larger than those in currently marketed COCs; therefore generalizability is limited.
Combined versus progestin‐only oral contraceptives
The two studies in this group included an older multisite trial of OCs containing different progestins (WHO 1984) and a recent trial that compared OCs containing the same progestin (Espey 2012). The report of WHO 1984 provided data on milk volume, but did not have sufficient data to analyze infant growth in this review. Also, data on milk composition were presented by center, not for the full trial. Espey 2012 examined infant growth and breastfeeding continuation.
-
WHO 1984 (n = 171) compared a COC containing levonorgestrel 150 μg plus ethinyl estradiol 30 μg versus a POP containing norgestrel 75 μg. Breast milk volume was determined by pump expression using standardized procedures. The participants breastfed their infants in the morning, waited two hours, and pumped milk while simultaneously nursing from the other breast for 20 minutes. The process was repeated two hours later, using the opposite breast for pumping. The 'average' amount was then presented. Mean milk volume (mL) was lower for the COC group than for the POP group at 9 weeks (MD ‐17.80, 95% CI ‐28.80 to ‐6.80), 16 weeks (MD ‐24.00, 95% CI ‐34.53 to ‐13.47), and 24 weeks (MD ‐24.90, 95% CI ‐36.01 to ‐13.79) (Analysis 7.1). Declines began after study initiation at six weeks postpartum and continued throughout the trial. From week 6 through week 24, average milk volume for COC users declined by 42% versus 12% among POP users. The randomized groups were not significantly different in infant weight change; sample sizes were not available for analysis (Analysis 7.2). Biochemical composition of breast milk was presented by center, not for the total sample. Differences within centers were small and inconsistent. Increases in milk lipid among combined contraceptive users in one center are of unknown clinical significance.
-
Espey 2012 (n = 197) compared a COC containing norethindrone 1 mg plus ethinyl estradiol 35 μg versus a POP containing norethindrone 350 μg. The trial was powered to assess differences in continuation of breastfeeding. The investigator provided means and standard deviations for actual change and percentage change in infant weight and length. The study groups did not differ significantly for mean change in infant weight (Analysis 8.1) or in infant length (Analysis 8.2) from week two to week eight. The groups did not differ significantly at two or eight weeks for supplementing with formula. Results for the Cox proportional hazard regression indicate that the intervention group was not statistically associated with breastfeeding discontinuation (Analysis 8.3). The regression included the covariates of OC history and breastfeeding history due to baseline differences. However, formula supplementation and concerns about milk supply were associated with breastfeeding discontinuation (reported P = 0.033 and 0.005, respectively). No pregnancies were reported by eight weeks.
Discussion
Summary of main results
Most trials did not show or report significant differences between study arms in breastfeeding duration, breast milk composition, or infant growth (Table 2). The few exceptions were seen mainly in older studies with limited reporting.
-
Breastfeeding continuation was studied in eight trials. One older study noted a negative effect of a combined oral contraceptive (COC) on lactation duration but did not quantify results. An early trial of a levonorgestrel‐releasing intrauterine system (LNG‐IUS) showed a lower percentage of the LNG‐IUS group breastfeeding at 75 days but no significant difference at one year. The other five trials indicated no significant differences between the study arms. Of those five, two studied insertion times for the etonogestrel‐releasing (ETG) implant, one compared a COC versus a progestin‐only pill (POP), and two examined the LNG‐IUS. Of the latter, one compared the LNG‐IUS versus a nonhormonal intrauterine device (IUD); the other compared insertion times and was stopped early because of expulsion rates.
-
Milk volume or composition was examined in six trials. Two older studies indicated conflicting effects of a COC on milk volume, but neither quantified results. Another older trial showed lower volume for the COC versus POP group. Two placebo‐controlled trials reported no significant effect of a POP on breast milk volume or composition, although one did not quantify results, and the other did not provide sample sizes for analysis. An ETG implant study showed no significant effect of early versus standard insertion.
-
Infant growth was assessed in seven trials. One showed greater infant weight gain for the ETG implant group than for the no‐method group during the first six weeks. The implant group had less weight gain from 6 to 12 weeks when compared to those given depot medroxyprogesterone acetate (DMPA). The other six studied POPs only, COCs versus POPs, or the LNG‐IUS, and indicated no significant differences between groups. Trial reports did not present the amount of supplemental feeding provided to the infants.
-
Pregnancy was self‐reported. One trial showed a lower percentage in the POP group. Three had no pregnancy in either group; they examined an LNG‐IUS or a COC and POP.
Sensitivity analysis
This analysis was restricted to six studies that provided sufficient data and moderate‐quality evidence (Table 3). Two examined the LNG‐IUS, with one comparing it with a nonhormonal IUD and one examining insertion times. Two trials studied insertion times for the ETG implant, and two examined a COC versus a POP. Five of the six trials were published since 2005.
-
Lactation duration: The five trials that examined breastfeeding duration indicated no significant differences between the study groups.
-
Breast milk volume or composition: One study showed a negative effect of the COC versus a POP on milk volume (mL expressed) through 24 weeks postpartum (mean difference (MD) ‐24.90, 95% confidence interval (CI) ‐36.01 to ‐13.79), and a recent implant trial showed no significant difference between insertion times.
-
Infant growth: Three trials indicated no significant differences in weight or length. One trial showed greater weight gain in the ETG implant group compared with the no‐method group at six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less gain compared with the DMPA group at 12 weeks (MD ‐271.00, 95% CI ‐355.10 to ‐186.90).
Overall completeness and applicability of evidence
Most studies assessed breastfeeding duration (full or any) or breast milk volume or composition as well as infant growth. Four examined self‐reported pregnancy. Time frames for contraceptive initiation in the experimental group varied: one to three days after delivery in five trials (implant, LNG‐IUS, and OCs); two weeks postpartum in two trials (OCs); and approximately six weeks postpartum in four trials (OCs or IUS). Follow‐up ranged from 10 days (oldest trial) to one year (more recent studies).
Studies were conducted in Asia, Europe, North Africa, and the Americas. Five trials published before 1985 included a multicenter trial conducted in Hungary and Thailand and four other trials from Finland, Germany, Mexico, and the United States. Six newer trials, published from 2005 to 2014, were conducted in Brazil, Egypt, India, and the United States (three studies).
Inclusion and exclusion criteria varied among trials. Most studies were limited to healthy women with birth at 37 weeks gestation or later. Some trials included any woman intending to initiate breastfeeding, whereas others were limited to women who planned to breastfeed exclusively (Brito 2009) or for a minimum duration (Miller 1970; Stuart 2014), had previously breastfed successfully (WHO 1984), or were exclusively breastfeeding at the time of randomization (Shaamash 2005).
The evidence was limited for any particular hormonal method. Four trials examined COCs: two versus placebo and two versus a POP. Three of the four studies were at least 30 years old and had limited reporting. Older studies used hormonal preparations and doses that may be applicable to contemporary practice. Seven trials focused on progestin‐only methods. Two studied a POP versus placebo; the recent one was a preliminary report. Two trials compared ETG implant insertion times. Three examined an LNG‐IUS (one had an older IUS); two compared the LNG‐IUS versus a nonhormonal IUD, and one compared insertion times. We did not find any RCTs of a vaginal ring or a transdermal patch among lactating women. A trial of emergency contraception as a backup for the lactational amenorrhea method did not include data on our primary outcomes (Shaaban 2013).
This review examined infant growth rather than development or other health outcomes. Two included trials assessed infant health issues at 12 months. In Heikkilä 1982, the LNG‐IUS and Nova T groups did not differ significantly for incidence of otitis media and respiratory infection as reported by the mothers. Shaamash 2005 assessed 19 infant development items, grouped as gross motor, vision and fine motor, hearing and language, self‐help skills, and social skills (WHO 1986). No significant difference was noted between the LNG‐IUS and CuT 380A groups in time to pass any test. An earlier non‐randomized study of progestin‐only methods used the same 19 items (WHO 1994). The investigators found a few differences that were mainly site‐specific but no consistent trends. The progestin‐only methods apparently had no negative effect on infant development. A systematic review of mainly observational studies came to the same conclusion (Kapp 2010a). In a review of combined oral contraceptives, the limited evidence indicated no adverse health outcomes in infants (Kapp 2010b).
Quality of the evidence
The quality of reporting varied over time. The earlier publications often provided little detail on methodology and provided insufficient data on results. Standards for publishing trials were developed in the late 1990s, and the CONSORT statement was widely adopted in 2010 (Schulz 2010). We summarized the quality of evidence from the individual trials (Table 1). Overall, the quality was considered moderate. The lower‐quality evidence, often due to limited reporting, came from three of the four placebo‐controlled trials of oral contraceptives.
Half of the trials provided inadequate information on randomization and allocation concealment. Two trials had high losses to follow‐up (WHO 1984; Espey 2012). Loss to follow‐up greater than 20% threatens trial validity (Strauss 2005). Two trials with moderate‐quality evidence provided insufficient or inconsistent data (Miller 1970; Heikkilä 1982). One trial was terminated early because expulsion rates met a priori stopping rules (Stuart 2014). The resulting sample size was much smaller than was planned, so the trial was underpowered to detect differences between groups in breastfeeding outcomes.
Agreements and disagreements with other studies or reviews
Two systematic reviews of hormonal contraceptives and lactation included studies of various designs (Kapp 2010a; Kapp 2010b). Progestin‐only methods did not appear to negatively affect lactation (Kapp 2010a). The evidence was limited and inconsistent for COCs and breastfeeding (Kapp 2010b). For infant growth and health, the evidence for progestin‐only methods was consistent though limited but did not appear to show an adverse effect. The evidence for COCs was considered inadequate at the time for assessing the effect on infant health. Another systematic review found limited evidence regarding medroxyprogesterone use and breastfeeding at less than six weeks postpartum (Brownell 2012). Only three studies of limited quality were eligible and none adjusted for potential confounding. A non‐randomized study of hormonal contraceptives and lactation examined a COC, the LNG‐IUS, the etonogestrel implant, and a nonhormonal IUD (CuT 380A) initiated at 42 days postpartum (Bahamondes 2013). Participants had previously breastfed and were willing to breastfeed exclusively and on demand for the study duration. The investigators reported no significant differences between the study groups from 42 days to 63 days postpartum in infant milk intake, infant weight or height, or breastfeeding (also assessed at six months).
We did not review the evidence for venous thromboembolism (VTE) risk, which was a factor in developing medical eligibility criteria for hormonal contraceptive use by postpartum women (WHO 2009; CDC 2011). Physiological risk of VTE is high in the postpartum period, especially for the first three weeks, and declines by six weeks' postpartum (WHO 2010). However, direct evidence is lacking for risk of VTE with combined hormonal contraception.
Study flow diagram (2014).
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
| Study | LNG‐IUS | Nova T | Reported P |
| Heikkilä 1982 | 56% | 79% | < .05 |
Comparison 1 LNG‐IUS (30 μg) versus nonhormonal IUD (Nova T), Outcome 1 Breastfeeding continuation at 75 days.
| Study | LNG‐IUS | Nova T | Reported P |
| Heikkilä 1982 | 197 + 141 | 208 + 104 | not significant (NS) |
Comparison 1 LNG‐IUS (30 μg) versus nonhormonal IUD (Nova T), Outcome 2 Mean days of breastfeeding (over 12 months).
| Study | Time frame | LNG‐IUS | CuT 380A | Reported P |
| Shaamash 2005 | 6 months | 7225 + 810 | 7157 + 759 | NS |
| Shaamash 2005 | 12 months | 9284 + 423 | 9183 + 421 | NS |
Comparison 2 LNG‐IUS (20 μg) versus nonhormonal IUD (CuT 380A), Outcome 1 Reported mean infant weight (g).
| Study | Time frame | LNG‐IUS | CuT 380A | Reported P |
| Shaamash 2005 | 6 months | 65.1 + 3.2 | 64.4 + 3.0 | NS |
| Shaamash 2005 | 12 months | 72.6 + 3.2 | 72.3 + 3.9 | NS |
Comparison 2 LNG‐IUS (20 μg) versus nonhormonal IUD (CuT 380A), Outcome 2 Reported mean infant length (cm).
| Study | Time frame | LNG‐IUS | CuT 380A |
| Shaamash 2005 | 6 months | 16.5 + 3.4 | 19.9 + 3.6 |
| Shaamash 2005 | 12 months | 0.3 + 0.4 | 0.0 + 0.0 |
Comparison 2 LNG‐IUS (20 μg) versus nonhormonal IUD (CuT 380A), Outcome 3 Reported net cumulative rate for full breastfeeding.
| Study | Time frame | LNG‐IUS | CuT 380A |
| Shaamash 2005 | 6 months | 90.6 + 2.3 | 93.5 + 2.0 |
| Shaamash 2005 | 12 months | 89.3 + 2.5 | 90.9 + 2.3 |
Comparison 2 LNG‐IUS (20 μg) versus nonhormonal IUD (CuT 380A), Outcome 4 Reported net cumulative rate for continuation of IUS or IUD.
Comparison 3 LNG‐IUS insertion time after delivery: 48 hours versus 4 to 6 weeks, Outcome 1 Any breastfeeding at 6 months.
Comparison 4 Etonogestrel implant (at 24 to 48 hours) versus no method until 6 weeks, Outcome 1 Exclusive breastfeeding.
Comparison 4 Etonogestrel implant (at 24 to 48 hours) versus no method until 6 weeks, Outcome 2 Mean change in infant weight (g).
Comparison 5 ETG implant (at 24 to 48 hours) versus DMPA from 6 to 12 weeks, Outcome 1 Exclusive breastfeeding.
Comparison 5 ETG implant (at 24 to 48 hours) versus DMPA from 6 to 12 weeks, Outcome 2 Mean change in infant weight (g).
Comparison 6 Etonogestrel implant: early versus standard insertion, Outcome 1 Lactation failure.
Comparison 6 Etonogestrel implant: early versus standard insertion, Outcome 2 Mean time to lactogenesis stage II.
Comparison 6 Etonogestrel implant: early versus standard insertion, Outcome 3 Mean creamatocrit of breast milk at 6 weeks.
Comparison 6 Etonogestrel implant: early versus standard insertion, Outcome 4 Breastfeeding fully.
Comparison 6 Etonogestrel implant: early versus standard insertion, Outcome 5 Breastfeeding, any.
Comparison 7 COC (levonorgestrel 150 μg + EE 30 μg) versus POP (norgestrel 75 μg), Outcome 1 Mean breast milk volume (mL).
| Study | Visit interval | COC | POP |
| WHO 1984 | Mean + | Mean + SE | |
| WHO 1984 | 6 to 9 weeks | 561.9 + 24.4 | 623.5 + 23.5 |
| WHO 1984 | 9 to 12 weeks | 523.0 + 24.3 | 531.9 + 23.2 |
| WHO 1984 | 20 to 24 weeks | 354.6 + 19.9 | 395.7 + 19.8 |
Comparison 7 COC (levonorgestrel 150 μg + EE 30 μg) versus POP (norgestrel 75 μg), Outcome 2 Mean change in infant weight (g).
Comparison 8 COC (norethinodrone 1 mg + EE 35 μg) versus POP (norethinodrone 350 μg), Outcome 1 Mean change in infant weight (kg) from week 2 to 8.
Comparison 8 COC (norethinodrone 1 mg + EE 35 μg) versus POP (norethinodrone 350 μg), Outcome 2 Mean change in infant length (cm) from week 2 to week 8.
| Study | Variable | Reported | Reported | Reported |
| Espey 2012 | Group: COC versus POP | 1.42 | 0.76 to 2.65 | .270 |
| Espey 2012 | Supplementing: yes versus no | 2.81 | 1.09 to 7.23 | .033 |
| Espey 2012 | Milk concerns: yes versus no | 2.07 | 1.37 to 5.91 | .005 |
Comparison 8 COC (norethinodrone 1 mg + EE 35 μg) versus POP (norethinodrone 350 μg), Outcome 3 Breastfeeding discontinuation by 6 months.
| Study | Comparison groups | Inadequate | No blinding | Follow‐up: | Loss to follow‐up | Quality of evidencea |
| Progestin‐only pills (POPs) versus placebo | ||||||
|
| ‐1 | ‐‐‐ | ‐1 | No information | Low | |
|
| ‐1 | No information | ‐‐‐ | No information | Low | |
| Levonorgestrel‐releasing intrauterine system (LNG‐IUS) | ||||||
|
| ‐1 | ‐‐‐ | ‐‐‐ | ‐‐‐ | Moderate | |
|
| ‐‐‐ | No information | ‐‐‐ | No information | Moderate | |
| LNG‐IUS (20 μg), insertion times
| ‐‐‐ | ‐1 | ‐‐‐ | ‐‐‐ | Moderate | |
| Etonogestrel‐releasing (ETG) implant, early versus standard insertion | ||||||
|
| ‐‐‐ | ‐1 | ‐‐‐ | ‐‐‐ | Moderate | |
| ETG implant, postpartum insertion time
| ‐‐‐ | ‐1 | ‐‐‐ | ‐‐‐ | Moderate | |
| Combined oral contraceptive (COC) versus placebo | ||||||
|
| ‐1 | No information | ‐1 | No information | Very low | |
|
| ‐1 | ‐‐‐ | ‐‐‐ | ‐‐‐‐ | Moderate | |
| Combined oral contraceptive versus progestin‐only pill | ||||||
|
| ‐‐‐ | ‐‐‐ | ‐‐‐ | ‐1 | Moderate | |
|
| ‐‐‐ | ‐‐‐ | ‐‐‐ | ‐1 | Moderate | |
| Overall quality of evidence | Moderate | |||||
| aGrade levels were high, moderate, low, or very low. RCTs were downgraded by one level for each of the following: (1) no information on randomization sequence generation or allocation concealment, or one was clearly inadequate; (2) no blinding; (3) follow‐up < 8 weeks for infant growth or < 12 weeks for lactation; (4) loss to follow‐up > 20%; (5) information missing for both blinding and losses. | ||||||
| Study | Comparison groupsa | N | Postpartum initiation | Lactationb | Breast milkc | Infant growthd | Pregnancy |
| Progestin‐only pill (POP) versus placebo | |||||||
|
| 20 | 48 hours | ‐‐‐ | NSe; not quantified | NSe; not quantified | ‐‐‐ | |
|
| 400 | 6 weeks | ‐‐‐ | NSe | NSe | POP < placeboe | |
| Levonorgestrel‐releasing intrauterine system (LNG‐IUS) | |||||||
|
| 80 | 6 weeks | BFe: LNG‐IUS < Nova T IUD | ‐‐‐ | NSe; not quantified | None | |
|
| 320 | 6 to 8 weeks | NSe | ‐‐‐ | NSe | None | |
| LNG‐IUS (20 μg), insertion times
| 35 | 48 hours vs | NS | ‐‐‐ | ‐‐‐ | ‐‐‐ | |
| Etonogestrel‐releasing (ETG) implant: early versus standard insertion | |||||||
|
| 40 | 24 to 48 hours vs 6 weeks | NS | ‐‐‐ | Weight: | ‐‐‐ | |
| ETG implant insertion
| 69 | 1 to 3 days vs 4 to 8 weeks | NS | NS | ‐‐‐ | ‐‐‐ | |
| Combined oral contraceptive (COC) versus placebo | |||||||
|
| 100 | 1 day | NSe; not quantified | NSe; not quantified | ‐‐‐ | ‐‐‐ | |
|
| 50 | 14 days | BFe: COC < placebo; unclear, not quantified | Volumee: COC < placebo; unclear, not quantified, | ‐‐‐ | ‐‐‐ | |
| Combined versus progestin‐only oral contraceptive | |||||||
|
| 171 | 6 weeks | ‐‐‐ | Volume: COC < POP | NSe | ‐‐‐ | |
|
| 197 | 2 weeks | NS | ‐‐‐ | NS | None | |
| aTable shows direction of significant differences (reported or analyzed); NS = not significantly different. | |||||||
| Studya | Comparison groups | N | Postpartum initiation | Lactationb | Breast milkc | Infant growth |
| Levonorgestrel‐releasing intrauterine system (LNG‐IUS) | ||||||
|
| 320 | 6 to 8 weeks | NSd: | ‐‐‐ | NSd: weight (Analysis 2.1) and length Analysis 2.2) | |
| LNG‐IUS (20 μg) insertion times
| 35 | 48 hours vs | NS: | ‐‐‐ | ‐‐‐ | |
| Etonogestrel‐releasing (ETG) implant: early versus standard insertion | ||||||
|
| 40 | 24 to 48 hours vs 6 weeks | NS: | ‐‐‐ | Weight: | |
| ETG implant, postpartum insertion
| 65 | 1 to 3 days vs 4 to 8 weeks | NS: | NS: | ‐‐‐ | |
| Combined (COC) versus progestin‐only (POP) oral contraceptive | ||||||
|
| 171 | 6 weeks | ‐‐‐ | Volume: | NSd: | |
|
| 179 | 2 weeks | NS: | ‐‐‐ | NS: | |
| aIncludes studies with moderate‐quality evidence (Table 1) and sufficient outcome data (Table 2). Direction of significant differences shown (reported or analyzed); NS = not significantly different. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Breastfeeding continuation at 75 days Show forest plot | Other data | No numeric data | ||
| 2 Mean days of breastfeeding (over 12 months) Show forest plot | Other data | No numeric data | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Reported mean infant weight (g) Show forest plot | Other data | No numeric data | ||
| 2 Reported mean infant length (cm) Show forest plot | Other data | No numeric data | ||
| 3 Reported net cumulative rate for full breastfeeding Show forest plot | Other data | No numeric data | ||
| 4 Reported net cumulative rate for continuation of IUS or IUD Show forest plot | Other data | No numeric data | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Any breastfeeding at 6 months Show forest plot | 1 | 35 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.43 [0.38, 5.44] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Exclusive breastfeeding Show forest plot | 1 | 40 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.35 [0.32, 35.36] |
| 2 Mean change in infant weight (g) Show forest plot | 1 | 40 | Mean Difference (IV, Fixed, 95% CI) | 426.0 [58.94, 793.06] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Exclusive breastfeeding Show forest plot | 1 | 40 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.89 [0.38, 9.27] |
| 2 Mean change in infant weight (g) Show forest plot | 1 | 40 | Mean Difference (IV, Fixed, 95% CI) | ‐271.0 [‐355.10, ‐186.90] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Lactation failure Show forest plot | 1 | 69 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.18 [0.13, 80.79] |
| 2 Mean time to lactogenesis stage II Show forest plot | 1 | 69 | Mean Difference (IV, Fixed, 95% CI) | ‐0.90 [‐9.90, 8.10] |
| 3 Mean creamatocrit of breast milk at 6 weeks Show forest plot | 1 | 69 | Mean Difference (IV, Fixed, 95% CI) | 0.70 [‐0.76, 2.16] |
| 4 Breastfeeding fully Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 4.1 At 6 weeks | 1 | 65 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.23 [0.46, 3.28] |
| 4.2 At 3 months | 1 | 63 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.45, 3.45] |
| 4.3 At 6 months | 1 | 61 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.88 [0.28, 2.74] |
| 5 Breastfeeding, any Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 5.1 At 6 weeks | 1 | 65 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.08 [0.55, 17.18] |
| 5.2 At 3 months | 1 | 63 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.13 [1.00, 9.77] |
| 5.3 At 6 months | 1 | 57 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.42 [0.50, 4.03] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mean breast milk volume (mL) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1 At 9 weeks | 1 | 161 | Mean Difference (IV, Fixed, 95% CI) | ‐17.80 [‐28.80, ‐6.80] |
| 1.2 At 16 weeks | 1 | 140 | Mean Difference (IV, Fixed, 95% CI) | ‐24.0 [‐34.53, ‐13.47] |
| 1.3 At 24 weeks | 1 | 115 | Mean Difference (IV, Fixed, 95% CI) | ‐24.90 [‐36.01, ‐13.79] |
| 2 Mean change in infant weight (g) Show forest plot | Other data | No numeric data | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mean change in infant weight (kg) from week 2 to 8 Show forest plot | 1 | 81 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.30, 0.10] |
| 2 Mean change in infant length (cm) from week 2 to week 8 Show forest plot | 1 | 81 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [‐0.48, 1.02] |
| 3 Breastfeeding discontinuation by 6 months Show forest plot | Other data | No numeric data | ||
