Methods and Success Factors of Induced Lactation: A Scoping Review

Background Induced lactation enables a woman who has not given birth to breastfeed a child. Lactation may be induced through both pharmacological and non-pharmacological methods, although the desired outcome cannot always be achieved. Research Aims The aims of this scoping review was to assess the different methods used to induce lactation, as well as the factors related to sucking the breast effectively and the production of human milk. Methods We searched five databases from June 2019–February 2020 for studies referring to methods and factors related to breast suckling and/or the volume of milk produced after inducing lactation, using the following search terms and Boolean operators: breastfeeding AND induced lactation AND adoptive mothers OR surrogate mothers OR female homosexuality OR non-gestating. The final review included a total of 24 articles. Results Pharmacological methods were not always used to produce milk, although breast stimulation was essential. The age of the child, interference due to bottle feeding, breast stimulation, and the support received were important factors in the induction of lactation. There were several factors that may account for the differences between developing and higher income countries in methods of induced lactation and the amount of milk that study participants produced. There was no consensus over whether previous pregnancy and/or breastfeeding experience influenced induced lactation. Conclusion Health professionals need to have adequate knowledge about induction methods, the preferences of each woman, and the reasons for inducing lactation, to provide proper assistance. However, the lack of standardization about induction of lactation makes it difficult.


Background
There are two stages in milk production that are related to hormonal processes during pregnancy and upon delivery. During pregnancy, estrogens stimulate the proliferation and differentiation of mammary glands and ducts, while progesterone causes the growth of lobes and alveoli and inhibits lactation. At the time of the birth, a rapid fall in the levels of these hormones disinhibits prolactin secretion, the increase in which triggers milk secretion. Suckling by the newborn helps to maintain lactation and is accompanied by the production of oxytocin, which causes contraction of the mammary epithelium and the ejection of milk (Truchet & Honvo-Houéto, 2017).
Induced lactation is the process whereby a woman who has not recently been pregnant or who is not nursing another child produces milk (Sriraman, 2017). If they have previously breastfed, it is termed relactation (World Health Organization [WHO], 1998). The main reasons why women induce lactation is to develop closeness between mother and child and/or to satisfy the child's nutritional needs. The reasons and methods for inducing lactation vary in different countries (Rahim et al., 2017).
Difference in the duration of breastfeeding between developing and higher income countries may be due to the different reasons why lactation is induced: ensuring the child's survival through the provision of human milk prior to introducing other foods, in developing countries, as opposed to strengthening the closeness between mother and child in high income settings (Gribble, 2007;Ogunlesi et al., 2008).
Adoption is historically known as the legal process to achieve parenthood without delivery. The growth and development of assisted reproduction techniques have allowed other options of motherhood, including surrogacy or pregnancy in a female same-sex couples (Gürtin et al., 2018). These new family structures have increased in recent years, thereby increasing rates of breastfeeding due to lactation being induced (Schnell, 2015), although women who adopt a child, who have a child through surrogacy, or who are the non-pregnant partners in a lesbian couple, may be able to breastfeed. However, it has been reported that many of these new family structures have found a lack of support during the process from nurses and physicians (Chuisano & Anderson, 2019).
Providing all women who wish to breastfeed with adequate support and advice should be a priority for health professionals and would contribute to better health in both the woman and child, with increased rates of breastfeeding (Kornides & Kitsantas, 2013;Chetwynd et al., 2019). We define breastfeeding for the child as the consumption of human milk including expressed milk and milk from a wet nurse and other food or liquid (Noel-Weiss et al., 2012).
Despite the increased desire for induced lactation, many health professionals do not have precise knowledge about induced lactation and may feel insecure when faced with a request for advice. The aim of this scoping review was to assess the different methods used to induce lactation, as well as the factors related to sucking the breast effectively and the production of human milk.

Design
We conducted a scoping review, which allows researchers to identify knowledge gaps, scope a body of literature, and clarify concepts (Munn et al., 2018). We have followed the five stage-process proposed by Pham et al. (2014), based on Arksey and O'Malley (2005): (1) identify the research question; (2) identify relevant studies; (3) study selection; and (4) collate, summarize, and report the results.

Sample
Articles were selected if they contained information about the methods used to induce lactation, and the factors associated with suckling the breast effectively and the volume of milk produced after inducing lactation. Inclusion criteria were: (1) articles with information about the methods used to induce lactation; (2) articles with information about the factors associated with suckling the breast effectively and/or the volume of milk produced after inducing lactation; (3) English or Spanish language articles; and (4) due to the relevance of studies published in the 1980s, we decided to include studies published during the last 39 years. Exclusion criteria were: (1) nonclinical studies; (2) non-human studies; (3) reports not written in either English or Spanish; (3) letters; (4) protocols; (5) reviews; and (6) clinical guidelines. The sample selection process is explained in Figure 1. The total sample was 24 articles.

Data Collection
The literature search was conducted from June 2019-February 2020 by the first author, using the following databases: Pubmed, Web of Science Cumulative Index to Nursing and Alice Health Literature (CINAHL), JSTOR, and Psycinfo. The following search terms and Boolean operators were used: Breastfeeding (under alternative spellings e.g., breast feeding and breast-feeding) AND induced lactation AND adoptive mothers OR surrogate mothers OR female homosexuality OR non-gestating. Two authors read the 98 abstracts to determine if the articles met the inclusion criteria. From September-October 2019 They then carefully read the selected articles to extract data on methods and success factors in induced lactation.

Data Analysis
We drew up a table in order to classify the 24 articles according to the following variables: (1) first author and year of publication; (2) context of induced lactation; (3) study design; (4) country in which the study was conducted; (5) number of participants (and their characteristics); (6) methods of induction of lactation; and (7) main contributions to and factors associated with suckling the breast effectively

Key Messages
• Stimulation is essential to induce breastfeeding despite the use or not of pharmacological methods; however, no consensus exists regarding what methods should be used to continue breastfeeding.
• No standardized approach for women who decide to undergo induced lactation exists.
• Factors associated with the success of induced lactation are the age of the child, interference due to bottle feeding, breast stimulation, and the support received. and/or the volume of milk produced after inducing lactation.
The first author extracted data from each selected article. The context of induction refers to whether induction occurred in case of adoption, surrogacy, or in lesbian couples. The methods used could be pharmacological: hormonal treatment or galactagogues (including herbal galactagogues), or non-pharmacological stimulation (manual or mechanical stimulation or with at-breast suckling supported by a supplemental nursing system). In the results section of the studies we extracted the factors associated with suckling the breast effectively and/or the volume of milk produced after an induced lactation (if there was a reference in the article).

Results
A summary of variables extracted from each article is detailed in Table 1. These included demographic variables (e.g., country where the study was done, year of publication); study methods (e.g., design, sample size); and the outcome variables of interest for this review (e.g., method of induction, effectiveness of milk production) that are discussed below.

Methods for Inducing Lactation
Lactation may be induced through non-pharmacological methods (i.e., manual stimulation of the breasts, the use of breast pumps, or suckling by the child) or pharmacologically, via the administration of hormones (progesterone and estrogen) and/or galactagogues.

Non-Pharmacological Methods
In the study by Abejide et al. (1997), Nigerian women (N = 6) produced enough milk to feed their adopted child with breast stimulation alone. All participants had previously breastfed, between 9 months and 2 years prior to beginning the induction. In all cases, lactation was initiated by suckling the child at least 10 times each day for at least 10 min on each breast. These participants began to produce milk 13-18 days after initiating suckling, and after 21-28 days, the breastfeeding was exclusive in all cases. Gribble (2005)   Mixed BF for 4 weeks BF established bond between mother and child even if milk production was not sufficient. No change in prolactin levels. The mother's satisfaction and the importance of sharing the experience were key. Consider whether the success of induced lactation was EBF or simply producing any milk.
Wilson et al. 3) 1 yr No BF (n = 5) Bottle feeding was an obstacle for suckling at the breast. Induction of lactation was related to the attachment between mother and child. The success of induced lactation was related to the possibility of BF, milk produced.
Thearle and Weissenberger Mixed BF > 7 months Previous BF was related to longer duration of BF after induced lactation and less supplements. The main reason for inducing lactation was to strengthen attachment between mother and child. Children older than 8 weeks had more difficulty suckling. Not achieving EBF did not affect the experience of induced lactation.
Note. Main contributions included factors related to suckling effectively at the breast and/or the amount of milk produced. USA = United States of America; UK = United Kingdom; CAIS = Complete Androgen Insensitivity Syndrome; HT = hormonal treatment; G = Galactagogues; IO = intranasal oxytocin; S = stimulation; SNS = supplemental nursing system; BF = breastfeeding; EBF = exclusive breastfeeding; mixed BF = BF and formula; hx = history. described five cases of adopted children from 8 months to 5 years old who expressed desire to suckle, by looking for their adoptive mother's breast. In three of the five cases (60%) breastfeeding was achieved with only breast stimulation by suckling.

Pharmacological Methods
Combined Treatment with Hormones. The aim of combined treatment with estrogen and progesterone is to produce a state like pregnancy in women. Hormones cause changes in the mammary tissue, but impede lactation, and the treatment must be stopped at least 24-48 hr prior to beginning breast stimulation (Thearle & Weissenberger, 1984). Study participants began to take combination hormones 2.5-5 months before beginning breast stimulation; it was maintained for 6-10 weeks (Szucs et al., 2010;Wilson et al., 2015). In the study by Nemba (1994) the method used depended on whether the participants had previously breastfed a child. Those who had not were given an intramuscular injection of 100 mg of medroxyprogesterone 1 week prior to breast stimulation, and chlorpromazine 25 mg/4 times per day until lactation was well established. Participants who had previously breastfed were given either chlorpromazine, 25 mg/4 times a day, or metoclopramide, 10mg/4 times a day, until lactation was well established. Both groups stimulated the breasts through frequent suckling by the child. In the study by Thearle and Weissenberger (1984), the induction method varied depending on whether or not participants had a history of lactation. All women used a breast pump for stimulation, but three women (50%) who had not previously breastfed also were administered 2.5-40 mg of non-androgenic progesterone and between 0.05-0.4 mg of estrogen 12-28 weeks prior to beginning stimulation. In the case report (N = 2) by Wilson et al. (2015), 3 months before the baby's due date one of the participants (A) began taking drospirenone/ethinylestradiol, 3 mg/0.03 mg for 8 weeks. After the last dose she began pumping a minimum of 15 min 4 times a day, as well as drinking fenugreek tea. She also started taking domperidone during this period. The first drops of milk appeared on the 12th day of pumping, after which her production increased to a maximum of 64 ml/day. Starting 2.5 months before their baby's due date, Participant B took ethynodiol diacetate/ethinylestradiol, 1 mg/35 mcg for 6 weeks. On the 3rd week of birth control, she initiated domperidone, and on the 5th week, she began drinking the same herbal tea with fenugreek and taking two malunggay (moringa oleifera, a tree leaf used as a galactagogue) pills 3 times a day (Wilson et al., 2015).
After stopping the hormones, she pumped for a minimum of 15 min, 4-5 times per day. The first drops appeared 2 days after beginning stimulation, and her production reached a maximum of 26 ml/day. In the study by Cazorla-Ortiz et al. (2020), five (55.5%) of the nine participants, took progesterone and estrogen to induce lactation in addition to galactagogues and stimulation of the breasts.
Intranasal Oxytocin. Da Rocha et al. (2014) reported on three women who breastfed their adopted child. One of them (33.3%) used oxytocin (in addition to alfalfa and cinnamon tea) to encourage lactation. Oxytocin nasal spray was also used (just prior to stimulation with a breast pump and suckling by the child) by the two women in the case reports by, respectively, Hawke et al. (2005) and Cheales-Siebenaler (1999). Finally, in the study by Auerbach and Avery (1981), 14 (6%) of the 240 participants used intranasal oxytocin, together with breast stimulation, for 2 weeks after the child's arrival. In this group, it was often reported that milk production was more likely if the oxytocin nasal spray was used in combination with breast stimulation.
Galactagogues. The drug most widely used in the studies reviewed was metoclopramide, a dopamine antagonist. Doses ranged from 20-80 mg per day, and a low dose (5 mg/day) could be maintained while breastfeeding; alternatively, some women stopped taking metoclopramide after a period of between 10 days and 2 months (Banapurmath et al., 1993;Lakhkar, 2000;Biervliet et al., 2001;Shiva et al., 2010;Farhadi & Philip, 2017). In some cases, dopamine was used (dose 30-120 mg/day), either around Week 20 of the pregnancy or after the child was born (Hawke et al., 2005;Szucs et al., 2010;Reisman & Goldstein, 2018;LeCain et al., 2020;Mcguire, 2020). In the study by Zingler et al. (2017) and in the case report by Cheales-Siebenaler (1999), women stopped taking metoclopramide because of similar side effects: fatigue, weight gain, and emotional lability.
Herbal supplements with a galactagogue effect are sometimes used in combination with breast stimulation either with or without additional galactagogue or hormone treatment. An adoptive mother of twins took 1220-1830 mg of fenugreek and 340-1020 mg of blessed thistle (Szucs et al., 2010). One (33.3%) of the three participants combined breast stimulation with alfalfa, cinnamon tea, and an oxytocin nasal spray (Da Rocha et al., 2014). All participants included in this study combined stimulation with herbal galactagogues (Cazorla-Ortiz et al., 2020). In the case report about a mother whose baby was born through surrogacy with complete androgen insensitivity syndrome (CAIS), "the participant also took fenugreek and milk thistle as herbal supplements" (LeCain et al., 2020).

Factors Associated With Suckling the Breast Effectively and/or the Volume of Milk After an Induced Lactation
Successful induced lactation could be defined as achieving milk secretion, even if the quantity produced is insufficient for the exclusive breastfeeding of the child (Banapurmath et al., 1993;Shiva et al., 2010;LeCain et al., 2020). In this respect, success was more related to the mother's satisfaction and her sense of self-realization than to the amount of milk produced or the duration of breastfeeding (Cazorla-Ortiz et al., 2020;Cheales-Siebenaler, 1999;Zingler et al., 2017).

Factors Associated With the Mother's Satisfaction
Support/Encouragement by Health Personnel, Partner, Family and Friends. One of the main factors associated with the success of induced lactation was the support and encouragement the participants received during the process from health professionals. Health professionals played a key role in providing information, advising, and counseling women who had not been pregnant regarding the different methods to breastfeed their children. It was important to consider the woman's priorities and the particular family configuration Szucs et al., 2010;Wilson et al., 2015;Cazorla-Ortiz et al., 2020). This kind of support could be offered by an International Board Certified Lactation Consultants (Biervliet et al., 2001;Cazorla-Ortiz et al., 2020;Farhadi & Philip, 2017;Flores-Antón et al., 2017). In the report by Kirkman and Kirkman (2001) concerning a case of surrogate motherhood between two sisters, the support the sisters offered one another was what enabled them to continue with the induction process, despite the difficulties they encountered along the way. Gribble (2001) described an online support group for breastfeeding adoptive mothers. This resource helped participants to cope with feeling alone and provided both information and support through the sharing of experiences of induced lactation. Participants felt the process to be normal and socially acceptable, which was essential for a successful outcome. According to Nemba (1994), the mother who was motivated, confident in herself, and who was well-informed about the induction process, was more likely to achieve a successful outcome. In the study by Cazorla-Ortiz et al. (2020), participants felt that women who were breastfeeding without going through a process of induced lactation had more support than those who were breastfeeding after going through a process induced lactation.
Frequent Stimulation. Each breast had to be stimulated for 10-20 min, 4-10 times a day (including at night), and this could be done manually or by using a breast pump, or both (Banapurmath et al., 1993;Cazorla-Ortiz et al., 2020;Flores-Antón et al., 2017;LeCain et al., 2020;McGuire, 2018;Reisman & Goldstein, 2018;Szucs et al., 2010;Wilson et al., 2015). In the study by Lakhkar (2000), four (33.3%) of the 12 participants who began the process of induced lactation did not produce milk. It was suggested that this was due to a lack of motivation and insufficient breast stimulation. Although, in the study by Nemba (1994), some of the participants (N = 37) received pharmacological treatment during the induction process, one of the key factors in achieving high levels of prolactin and oxytocin was breast stimulation. In the cases of adoptive breastfeeding (N = 240) reported by Auerbach and Avery (1981), the most important factor in inducing lactation was nipple massage and stimulation, either by the child suckling or through use of a breast pump. Wilson et al. (2015) noted that breast stimulation could also be achieved when using a supplemental nursing system (SNS), in this case a bottle with a neonatal nasogastric tube was placed beside the mother's nipple that enabled the child to feed while simultaneously stimulating the breast; a bottle of this sort might contain formula, donor milk, or milk previously expressed by the mother herself (Banapurmath et al., 1993).

Previous Pregnancy and/or
Breastfeeding. In the study by Auerbach and Avery (1981) of adoptive mothers (N = 240), participants who had previously breastfed produced milk more quickly than did those with no history of lactation. In the recent case report by Mcguire (2020), the woman who induced lactation had had a previous pregnancy and lactation and achieved exclusive breastfeeding. In the study by Cazorla-Ortiz et al. (2020) two participants achieved exclusive breastfeeding without a previous pregnancy or breastfeeding, while the other two participants in the same study had previously breastfed but did not achieve exclusive breastfeeding.

Factors Associated With the Child
Child's Age. Auerbach and Avery (1981) reported that "three fourths of the babies less than 8 weeks of age responded well to the opportunity to nurse. Infants 8 weeks of age or older were as likely to accept as to reject the breast" (p. 342). Lakhkar (2000) likewise found that success was more likely the younger the child and the earlier that breastfeeding was initiated. However, Gribble (2005) described five cases of adopted children ranging from 8 months to 5 years old, who breastfed.
Interference Due to Bottle Feeding. The 10 children in the study by Banapurmath et al. (1993) were fed with formula until the mothers produced enough milk. Four of the children (40%) who had been bottle fed subsequently had problems taking to the breast; it was necessary to discontinue bottle feeding in order to achieve adequate suckling. In the event that formula or donor milk was needed as a supplement, this was given through a cup or spoon so as not to interfere with the child's suckling (Banapurmath et al., 1993;Nemba, 1994;Abejide et al., 1997).

Duration of Breastfeeding Following Induced Lactation
The longest reported cases of breastfeeding following induced lactation corresponded to middle-and high-income countries: mothers breastfed from 1 month to 4 years. In developing countries, mothers breastfed their children 4-12 months.

Discussion
There are several factors that may account for the differences between developing and higher income countries in methods of induced lactation and the amount of milk that mothers produce. Mothers in developing countries are generally more knowledgeable about breastfeeding, breastfeed more frequently, maintain close physical contact with their child, whose behavior they consequently learn to interpret, and have a history of breastfeeding that may also make it easier. They also live in a culture that is supportive of breastfeeding, not least as it is seen as crucial to children's survival, given the risks of infection associated with the preparation of formulas. As a result of the latter, there is also less interference due to bottle feeding or the use of dummies (Gribble, 2004).
Indeed, there is currently a tendency in the West to regard breastfeeding as a symbol of maternal identity (Schmied & Lupton, 2001). The "good" mother is one who breastfeeds her child, as by doing so she is seeking the best, both for her child and with regard to her own self-realization as a mother (Marshall et al., 2007;Lommen et al., 2015). The new family structures which are the result of same sex couples and the rise of assisted reproduction have led to an increase of induced lactation in both these situations; the maternity in same sex couples and in surrogacy (Imaz, 2017). Induction of lactation will gain importance and more studies about this process will be necessary.
Previous experience of breastfeeding appears to be an important, although not crucial, factor to achieve breastfeeding after inducing lactation. Prior breastfeeding strengthens the mother's intention to breastfeed, and her determination and self-efficacy to meet her goal, and provides her with a more realistic understanding of her breastfeeding intentions and expectations (Hackman et al., 2015). It should also be noted that in their study of the mouse mammary gland, Dos Santos et al. (2015) suggested that pregnancy is the major modulator of mammary gland activity and that the cells of this gland retain a memory of past pregnancies, which benefit future attempts at breastfeeding. In addition, information is lacking regarding whether there had been a previous pregnancy. Hermann (1977) reported that 36 of 65 adoptive mothers (55.38%) who induced lactation managed to produce milk prior to the child's arrival, and, of these, 12 (33.3%) had no history of pregnancy, four (11.1%) had previously been pregnant but had not breastfed, and 20 (55.5%) had previous experience of both pregnancy and breastfeeding. By contrast, Saari et al. (2014) carried out in-depth interviews with adoptive mothers who had induced lactation, and concluded that the potential for success did not differ between those women with previous experience of pregnancy and breastfeeding and those with no history of maternity.
The pharmaceutical and herbal galactagogues used to increase milk production have been associated with a number of side effects, including gastric problems, bradykinesia, drowsiness, trembling, lethargy, hypoglycaemia, dyspnoea, strong smelling urine, sweating, and even depression, although more studies are needed to assess these effects (McGuire, 2018). In the review by Bazzano et al. (2016), which included 18 studies involving both pharmaceutical galactagogues, metoclopramide and domperidone, and herbal galactagogues including Asparagusracemosus (shatavari), Coleus amboinicus L. (torbangun), fenugreek, garlic extract, and Moringa oleifera, participants who took domperidone reported dry mouth as the only side effect. In the articles included in our review, little reference is made to the side effects of the drugs used to induce lactation, therefore more articles analyzing this effect are necessary. In the same way, not all the articles selected in the review refer to the factors related to suckling the breast effectively and/or the amount of milk after an induction of lactation. Considering that the cases of induced lactation will increase, future studies should compare the different methods and the different factors related to the success of the induction of lactation and how to determine which are the most appropriate in each case.
The main limitation of the studies reviewed was the lack of current studies about induction of lactation. Most of the articles were case reports, which do not produce enough evidence to generalize results or build an evidence base. Additionally, most of the case reports were about induction of lactation in adoption. Further research is required to increase knowledge about methods of inducing lactation in non-pregnant women, the circumstances in which one method may be better than another, the possible side effects of galactagogues, and the factors associated with a successful outcome.

Limitations
One of the limitations of this review is that the studies reviewed are in English or Spanish, which limits the usability of the results. In addition, inclusion criteria limited articles with information about the methods used to induced lactation and the factors associated with suckling the breast effectively and/or the volume of milk produced after inducing lactation. Articles referring to other aspects of inducing lactation were not included.

Conclusion
Health professionals can use this review to learn more about the process of induced lactation. Raising awareness and offering women the help and advice they need, taking into account their particular family situation, is essential. Guidance of this kind can empower women and allow them