Introduction
Lactation is a natural and physiological process after childbirth. Breast milk is a perfect food for the right nutrition, and optimal growth for infants. Lactation which is the complementary part of the fertility process with important effects on maternal health is the standard method of feeding a baby [1, 2]. In the body of pregnant women, the level of prolactin hormone increases naturally, and as the time comes to delivery and the end of the pregnancy, the hormone increases, so that in the last quarter of the pregnancy, the breast begins to make colostrum. Colostrum is a yellow or light fluid that carries proteins and immune materials through the intercellular space to the baby's body [3]. These low-volume substance, including drugs, lymphocytes and immunoglobulins, protect the child from illness after birth. From about 30 to 40 hours after removing the placenta, the breast begins to make breast milk [4]. Various studies have shown that the lives of more than seven million children each year can be saved from deaths caused by diarrhea and acute respiratory infections, only through increased breastfeeding alone in the first four to six months of life [5].
Lactation contraindications: In spite of the many benefits of breastfeeding, breastfeeding contraindication is also necessary in some cases. In case of taking narcotic drugs, alcohol and benzodiazepines, or a sedative drug in mother, the infant should not be fed with breast-milk. Studies have shown that drug abuse is a major and increasing problem in most countries. According to the protocol of the country that was published by the Health Office of the Population, Family and Schools in 2011, opioids (such as opium, syrup, heroin, codeine and morphine), stimulants (such as cocaine, crack (heroin + Methamphetamine), amphetamine, methamphetamine (glass or crystal, ice, crack, gypsum, ecstasy (MDMA), nicotine and caffeine), Hallucinogenic substances (such as LSD), phencyclidine (PCP), ketamine, cannabis and compounds and similar substances (cannabis, grass, bang, marijuana) and tobacco (such as cigars, pip, hookahs and chops) are considered to be narcotics and their use causes serious damage to the fetus. ; In such cases, breast milk also causes serious complications for the baby [6]. In all countries, regardless of developmental level, breastfeeding is still the best way to begin a child's life, as long as the use of the drug does not affect the mother and fetus. Since, addition is the cause of many problems, substance abuse indirectly affects the developmental process of the fetus, and after birth, it also affects the baby by feeding breast milk [7].
According to the protocol provided by the Ministry of Health, Treatment and Medical Education on the management of drug dependence during pregnancy, childbirth and lactation, in dealing with drug dependent women, the potential risks of breast milk against benefits, should be evaluated for each case; and then the mothers should be informed of these dangers. The infants of these mothers should not breastfeed as much as possible. However, in cases that breast-feeding is done, it should preferably be given before or at least one to two hours after the last dose. The advice of the US Academy of Pediatric Medicine in 1983 was that methadone maintenance therapy in lactation would be only unproblematic if the mother's dose of methadone was not more than 20 mg per day. Although subsequent studies showed that in doses below 180 mg, the release of methadone in breast milk is low and the 20 mg limit is not scientific. Other studies have shown that lactation in mothers on methadone maintenance therapy can shorten the duration of neonatal abstinence syndrome [8].
Mothers who drink alcohol are also known to be harmful to breastfeeding. Although some reports suggest that there is no accurate relationship between the amount of alcohol consumed and the amount of damage to the baby (dose-response), other findings have shown that drinking one or more glasses of alcohol per day results in a 5-fold increase in the risk of infant low-weight at birth and a 2-fold increase in the risk of an early birth of the fetus. Reports have also shown that children who have been exposed to more than 12 grams of ethanol per day through breast-feeding up to one year old have been attenuated by indicators of mental development. Among the samples, children who had been exposed to two glasses of alcohol each day, had decreased IQ and learning difficulties at the age of 7 [9]. Even in some infants who had been prone to alcohol during pregnancy of the mother and before birth, abnormalities and neurological disorders were observed in motor skills and responsiveness to stimuli although they had normal growth. Also, among these samples, delusional disorientations in vision, speech, behavior, and delay in equilibrium behaviors (due to damage to the cerebellum) have been observed. On the other hand, children who are exposed to alcohol during the lactation period besides their fetal period also suffer from disorders such as ADHD, sleep disturbances, nutritional disorders, poor communication skills, and so on [9-12].
Infant Indications: Some infants have problems with classical galactosemia; in these cases, the infant does not have the ability to break breast milk. Classical hereditary galactosemia is one of the most common metabolic carbohydrate disorders that can be dangerous in infancy. The cause of this disease is the malformation of the galactose-phosphate uridylyltransferase enzyme (GALT deficiency). Infants infected with the disease have symptoms such as breastfeeding abstinence, vomiting, jaundice, sleep deprivation, etc., and have no ability to breastfeed [1]. Of course, in some cases, the infant abstain to breastfeed without a convincing reason.
Mother's Personal Choice: In many cases, mothers do not have a chance to breastfeed their infants because of their work [9]. Studies have shown that about 70% of mothers who return to work after giving birth, lactation has been very difficult for them, and they often have problems. In mothers who have full-time jobs or in high-paid and high-responsibility jobs, as well as in mothers who have returned immediately after childbirth, and there is no gap between delivery and restart of the work, the likelihood of lactation is much lower [14]. One of the ways to overcome this problem can be the change the employers' policy of some businesses to provide leave to lactating mothers. According to studies, there is a direct relationship between the time of postpartum leave and the length of breastfeeding of mothers. As long as mothers' rights are paid during lactation and economically secured, their psychological stresses are reduced and this affect the amount of milk production [14-16]. In a research carried out in 2004 in Bushehr Province, the second major cause of non-breastfeeding was the employment of the mothers. The amount of working hours, the absence time of mother at home and the type of work had the greatest impact on the lack of breastfeeding [15].
In some societies, because of their religious and cultural values ​​and specific norms, mothers refuse to breastfeed [5, 17, and 18]. One of the other factors in not feeding a baby with breast milk is that breastfeeding can be difficult, so that the mother has to stop breastfeeding.
Losing pregnancy or the birth of a dead infant: In cases of neonatal death at time of birth or after birth, the secretion of milk in the gland need to be stopped [4, 5, and 13]. The secretion of milk has a complicated mechanism. The high level of estrogen, progesterone and prolactin during pregnancy can stimulate anatomical growth of the breasts; with increasing levels of prolactin, lactose synthesis begins in the breast; prolactin concentrations continue to rise for weeks, and in women who lose their infant for any reason, this process continues to release the milk [18]. Schaubert and Kirk use the term "white tears" to describe a mother's milk in the mother that has lost infant; this interpretation well reflects the depth of mother's pain and sorrow that lost her baby [19]. Accordingly, in case of missing an infant, milk should be stopped in any way.
Psychological problems and depression of mother: It's known that losing a baby is one of the worst experiences of life. When the mother's love of affection is challenged with her child's death, it is an experience that may not only mean the loss of a new child, but it can be a defeat in transforming a woman into a mother [19]. When a mother loses her baby, she experiences depression and deep frustration. In this period, the pain caused by swelling and milk accumulation in the breast as a stressor increase depression and stress in the mother [18]. Usually, after the baby's death, due to depression and severe psychological pressures, the mother has pain and swelling in the breasts. In this situation, the sooner the milk production should be cut or reduced [16]. On the other hand, the baby may be alive and healthy, but the mother has problems such as schizophrenia, bipolar disorder, psychopathological history, mental retardation or the risk of recurrence of postpartum psychological problems. Given the use of drugs such as lithium and clozapine in such cases, it is better not to breastfeed [20].
Refusing to breastfeeding for any reasons causes swelling in the breast, and the lack of adequate drainage may lead to problems such as duct obstruction, breast swelling and severe pain [20]. Although in the absence of physical stimulation (for example, breastfeeding), lactation is stopped, when the pituitary-hypothalamus's axis sends a message to reduce milk secretion, this milk accumulation causes mastitis. Inflammation of the breast after delivery can cause puerperal fever in many women [5]. In this regard, although breast swelling plays its role naturally through a self-regulating mechanism to reduce lactation, one must also use breastfeeding suppression at the same time. When the breast is full of milk and is not sucked by a baby, a set of peptides and proteins causes the appearance of apoptotic phenomena in the epithelial cells of the lacrimal gland and helps reduce the milk's secretion. Over time, this process causes swelling in the breast to cause severe pain in the area [19]. Obviously, in these cases, there are many problems for the mother and the lactation should be suppressed in any way. Therefore, the present study was conducted with the aim of introducing the methods of lactation suppression in the world in comparison with the Sarem Hospital administrative protocol.
In this review article, the criterion for selecting articles was to examine the causes and indications of postpartum lactation suppression. The relevant issues were collected about the disadvantages and benefits of any of the methods of suppressing lactation. The keywords for lactation suppression, lactation suppression treatments, narcotic drugs in breastfeeding, lactation after prenatal period, neonatal lost, etc. were searched by referring to valid and scientific sites (Science Direct, Pubmed, Elsevier, Cochrane). Among the articles related to the discussed topics, main topics and existing treatments were collected.
Studies have shown that there are numerous pharmacological and non-pharmacological interventions for suppressing lactation, after the birth of the baby and getting rid of its symptoms. Despite wide-ranging studies in this area, there is no single guidance on how to get the best out of lactation suppression in postpartum.
Non-pharmacological methods and the use of complementary medicine: For many centuries, humans have used non-pharmacological interventions to suppress lactation after delivery. When non-breastfeeding by the baby causes the accumulation of milk in the alveoli and triggering the reflux of the secretion of milk inhibition inhibitors in the hypothalamus-pituitary, in a few days, it prevents the secretion of milk, the dilation of the alveoli causes pain and swelling of the breast that, until the 20th century, it was relieved with pain killer. This is the safest and best method of lactation suppression. The closure of the breast or bandaging, milk withdrawal from the breast with massage, restriction of food and fluids, the use of topical ointments such as Belladonna ointment on the breast and nipple, as well as tight closure of the breast have been effective strategies [1, 5]; later, due to the prohibition of breast tamping, The use of cabbage leaves (due to phytoestrogens) on the breast, jasmine, ice sac, egg and sugar closing on the inflated breast, etc. became prevalent [19, 21]. The use of morphine and codeine to reduce pain has also been another common practice [22]. Of course, there are other methods such as acupuncture, homeopathy, massage therapy and the use of electric pumps to drainage milk from the breast, which can reduce the inflammation and infection caused by milk in the breast [2, 19, and 21]. In one experiment, the effect of the leaf extract of the cabbage leaf treated as cream was tested on the breast of the breastfeeding mother. In comparison with placebo, the results indicated that the swelling and stiffness of the breast were affected by the contact of the cream and the level of lactation was reduced [23]. In another study, the effects of hot tea bag on the breast were studied in comparison with warm water compressors. The results of this study also showed that the secretion of milk on the nipples was limited [23].
Medicinal methods: Many pharmacological treatments are recommended for inhibition of lactation, which can be categorized into three main groups:
A) Estrogen compounds
The effect of estrogen on the mammary glands is not well known, but we know that it directly affects these glands. Estrogen is an important factor in inhibiting prolactin secretion. By 1960, estrogen compounds were used alone or in combination with androgens to suppress the milk. Studies have shown that these compounds are effective up to 40% [5]. However, the results suggest that breast milk has been more than expected when using these compounds, as well as complications such as pulmonary thromboembolism and thrombosis. In 1968, Stirrat et al. tested Stilboestrol (a strong synthetic estrogen) and investigated the effects of different doses on inhibition of breastfeeding. Their findings suggest that long-term use of estrogen compounds can be effective in inhibiting lactation. However, as a potent inhibitor with low side effects in the short term, it cannot have a good effect, and breast swelling is not completely eliminated with this drug [24]. ] Another long-acting estrogen compound is Quinestrol, which is given as a single dose at a dose of 4 mg immediately after delivery [25]. Ethinylestradiol / Testosterone is another drug combination that increases the estrogen effect on the hypothalamus and reduces prolactin secretion [25]. This decrease in the level of prolactin increases the risk of thromboembolism, stroke and myocardial infarction, the MI of consumption and CVA [5, 11].
B) Ergot drug compounds
1. Bromocriptins are mainly derived from the Ergot Group and are dopaminergic. Pathologically and physiologically, it causes hyper prolactinemia, an inhibitor of growth hormone secretion and even anti-Parkinson [20].
Bromocriptine (a dopamine antagonist) and potent prolactin inhibitors were prevalent in 1972. The drug should be continued for 10 to 14 days in order to prevent the return of lactation [1]. This medication puts its effect through inhibiting the release of prolactin from the anterior pituitary gland [18]. In a wide range of studies on the effects of bromocriptine, it was concluded that due to the side effects of this drug (high blood pressure, preeclampsia during pregnancy and a history of mental and psychological illnesses), it should be taken only when the physician prescribes and to eliminate swelling and severe pain in the breast, the non-prescription methods mentioned above should be used [4]. Due to the complications noted for bromocorophenins, other drugs are used to control lactation include estrogens in combination with progesterone or both, clomiphene, pyridoxine, prostaglandin E2, other dopamine agonists such as cabergoline and serotonin antagonists such as cyproheptadine tablets, methysergide and metergoline, all of which have been shown to have a variable effect on postpartum lactation inhibition [5].
2. Cabergolines: In the late 1980s, Cabergoline, a type of ergot medication and a direct stimulant of the brain's dopamine D2 receptors, which reduces the secretion of prolactin, with fewer side effects than bromocriptine, was introduced to the market and the results of its use was published in 1991 [5]. The US Food and Drug Administration banned the use of routine bromocriptine in postpartum period, while there were no apparent causes for its complications, and no health was proven. In a survey conducted by Nisha et al in 2005, 196 women who had abortion or dead neonate were randomly divided into two groups, and for their lactation suppression, a group was fed with 0.4 mg to 1 mg cabergolin and the other group, were given the estrogen-androgen compounds. The results indicated that one dose of cabergolin at a dose of 1 mg a day was significantly more effective in suppressing breastfeeding 24 to 72 hours after delivery, compared with the combination of estrogen-androgen [2]. In 2013, another study was conducted on the effect of cabergoline on suppression of breastfeeding. In that study, one of the main criteria for entering the study was the lack of use of blood pressure regulators and a lack of hypertension above 120 mm Hg. The results of that study showed that this drug should not be used for mothers who have had eclampsia and preeclampsia during pregnancy due to complications associated with high blood pressure. The best dose of the drug in 93.7% of lactating women using this drug for lactation control, was a dose of 1 mg once daily, and 27 hours after birth [1].
C) Sympathomimetic drugs
Pseudoephedrine is an amino sympathomimetic (adrenergic receptor) that directly stimulates the alpha-adrenergic receptors of the respiratory mucosa and dilates the vessels, decreasing the swelling of the mucous membrane of the nose, reducing the hyperemia and edema of the nasal congestion, opening up the airway (nose) and drainage Sinus and the opening of the Eustachian tube. Direct stimulation of β-adrenergic receptors may cause loose muscle relaxation. It is strictly forbidden for lactating women to take this medicine. In cases of suppression of breastfeeding, this drug, at a dose of 60 mg 4 times a day for the first 24 hours of lactation, can reduce the secretion of milk. The mechanism of action is that it can cause arterial and capillary contractions in the tissue region of the breast, and with a direct effect on dopamine D2 receptors, through dopaminergic effects with pituitary effects, it reduces prolactin and ultimately reduces the secretion of milk.
Contraindications to these drugs
A) Estrogens and venous thromboembolism: the overall risk of venous thromboembolism is 4.7 per 1,000. The risk of it in mothers who do not breast feed is 2.1 in 1000, which may also be associated with low levels of fluids and other factors. In a 1969 study, it was reported that thromboembolism in mothers who do not breastfeed is 13 times more likely than mothers breastfeeding, although the mother's age also contributes to this. The highest risk is in mothers over 35 and having operatine birth. Finally, after standardizing maternal equity and delivery method, it was concluded that higher risk of thromboembolism is more associated with the age of mother and type of delivery and not lactation.
B) Ergot derivatives (bromocripthens, cabergolins): These compounds are D2 antagonists and disrupt the dopaminergic order of the brain. As a result, women with a history of neurological and psychosomatic illness or a history of schizophrenia have been banned from using these drugs. Studies have shown that the use of this class of drugs causes abnormal mental states and disturbs the nervous system in these women [20].
C) Sympathomimetic drugs: The most common side effects associated with amphetamine-like drugs include stomach pain, anxiety, irritability, insomnia, tachycardia, cardiac arrhythmias, and dysphoria. These medications may also increase heart rate and blood pressure and cause tachycardia. Therefore, it is not recommended in lactating women and those who have had preeclampsia during pregnancy.
 
Conclusion
In unsuccessful deliveries, lactation in women continues; as a result, lactation must be stopped. Despite of the many studies that have been done on the use of different methods of lactation, in most cases, doctors recommend that lactation be stopped using complementary therapies. The protocol used at Sarem Hospital is the use of estradiol for lactation suppression, which is one of the good choices that can be made considering the availability of this drug, its effects on the mother's body, the results of drug administration, and so on. Based on this systematic review and its scientific evidence, the most reported impact on resources is the use of bromocriptine. Choosing the right method, taking into account the total mental and physical conditions of the mother, limits the few choices. The research on the mechanism of milk secretion and its methods of suppression is very wide and requires more research.

Acknowledgments
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Contribution of authors
Manijeh Hashemi Jam (First author), author of the article/main author/author of discussion (%60); Zahra Roustaei (Second author), author of the article/helper author/author of discussion (%40).