Evidencia de la estimulación de puntos de acupuntura en el tratamiento de la hipogalactia: revisión sistemática con metaanálisis / Evidence of the acupuncture points stimulation for the treatment of hypogalactia: a systematic review and meta-analysis

Objetivo: Realizar una revisión de la literatura para analizar si la estimulación de puntos de acupuntura aumenta la cantidad de leche producida durante la lactancia. Método: Se recopilaron estudios de cinco bases de datos electrónicas siguiendo las recomendaciones internacionales para la elaboración de revisiones sistemáticas y metaanálisis. Los criterios de elegibilidad fueron artículos de texto completo en inglés o español con diseño de ensayos clínicos y estudios observacionales, sin restricción en el tiempo de publicación, en los cuales se hubiera evaluado el efecto de la estimulación de puntos de acupuntura en la mejora de la cantidad de lactancia mediante acupuntura convencional, electroacupuntura, láser, agujas de fuego, estimulación manual, Tui Na o catgut. Dos autores extrajeron de forma independiente los datos de las características y los resultados principales de los estudios seleccionados para su inclusión. Se realizaron las evaluaciones de riesgo de sesgo y de calidad (GRADE). Para la síntesis cuantitativa se calculó la diferencia de medias estandarizada para cada estudio individual seleccionado y luego se combinaron los datos mediante un metaanálisis de efectos aleatorios. Resultados: En la presente revisión se incluyeron un total de 14 estudios, la mayoría de ellos mostraron riesgo de sesgo y una calidad moderada. El metaanálisis mostró que la estimulación manual del punto de acupuntura aumenta la cantidad de leche materna (DME 95% IC=1,63 [1,13-2,13]; p<0,0001). Conclusión: La literatura sugiere que la estimulación manual de puntos de acupuntura mejora la cantidad de leche producida durante de lactancia.(AU)

Objective: To perform a literature review aimed to analyze if acupoint stimulation increases lactation quantity. Method: Studies were collected from five electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. Eligibility criteria were full-text articles in English or Spanish with clinical trial design and observational studies, with no restriction on time of publication, in which the effect of acupoint stimulation on improving the quantity of lactation by conventional acupuncture, electroacupuncture, laser, fire needling, manual stimulation, tuina or catgut had been evaluated. Two authors independently extracted data for the characteristics and main outcomes of the studies selected for inclusion. The risk of bias (RoB 2 and Robins-I) and the quality assessments (GRADE) were performed. For the quantitative synthesis, the standardized mean difference was calculated for each individual study selected and then the data were combined using a random-effects meta-analysis. Results: A total of 14 studies were included in the present review. Most of the included studies exhibited some concerns in the risk of bias assessment. The quality of the studies was moderate. The meta-analysis showed that manual acupoint stimulation improves the lactation quantity (SMD 95% CI=1.63 [1.13-2.13]; p<0.0001). Conclusion: The literature suggests that manual stimulation of acupuncture points improves the amount of milk produced during lactation.(AU)

Off-label postpartum use of domperidone in Canada: a multidatabase cohort study.

BACKGROUND: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients. METHODS: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death. RESULTS: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41). INTERPRETATION: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.

European Network of Pregnancy Registers in Rheumatology (EuNeP)-an overview of procedures and data collection.

BACKGROUND: The collaborative initiative of the European Network of Pregnancy Registers in Rheumatology (EuNeP) aims to combine data available in nationwide pregnancy registers to increase knowledge on pregnancy outcomes in women with inflammatory rheumatic diseases (IRD) and on drug safety during pregnancy and lactation. The objective of this study was to describe the similarities and differences of the member registers. METHODS: From all registers, information about their structure and design was collected, as well as which parameters regarding demographics, maternal outcomes, treatment, course and outcome of pregnancy, and development of the child were available in the respective datasets. Furthermore, the current recruitment status was reported. RESULTS: The four registers (EGR2 (France), RePreg (Switzerland), RevNatus (Norway), and Rhekiss (Germany)) collect information prospectively and nationwide. Patients can be enrolled before conception or during pregnancy. To date, more than 3500 patients in total have been included, and data on 2200 pregnancies with an outcome are available. The distribution of diagnoses in the respective registers varies considerably, and only three entities (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) are captured by all the registers. Broad consistency was found in non-disease-specific data items, but differences regarding instruments and categories as well as frequency of data collection were revealed. Disease-specific data items are less homogeneously collected. CONCLUSION: Although the registers in this collaboration have similar designs, we found numerous differences in the variables collected. This survey of the status quo of current pregnancy registers is the first step towards identifying data collected uniformly across registers in order to facilitate joint analyses. TRIAL REGISTRATION: Not applicable.

Effects of Domperidone in Increasing Milk Production in Mothers with Insufficient Lactation for Infants in the Neonatal Intensive Care Unit.

Breast milk is the optimum for all infants, but hospitalization in the neonatal intensive care unit can cause separation of mothers and infants, which often interferes with milk secretion. Some reports show that domperidone is effective in promoting milk secretion. However, the Food and Drug Administration in the United States cautioned to not use domperidone for increasing milk volume because domperidone carries some risk of cardiac events, including QT prolongation, cardiac arrest, and sudden death. In contrast, it is used in Canada, Australia, and the United Kingdom with safety. The pharmacodynamics and pharmacokinetics of drugs may vary by race or ethnic origin, and it is not known whether domperidone is effective or safe for Japanese. In this study we report the effects of domperidone for Japanese mothers with insufficient lactation. Ten mothers were enrolled in a pilot study. After confirming that there were no abnormal findings on the electrocardiogram, the mothers were administered domperidone. Seven of 10 who took domperidone increased their milking volume. Prolactin was increased in 9 of 10 mothers. Adverse events were observed in two mothers, one headache and one abdominal pain; all symptoms were mild and improved promptly; and there were no adverse cardiac events. These results are consistent with reports from other countries. Domperidone may tentatively be considered effective for increasing milk secretion in Japanese mothers as in other populations. Our preliminary study of 10 cases indicates the need for further studies with larger sample sizes to assess the efficacy and safety of domperidone.

Evaluating the Effect of a 14-Day Course of Domperidone on Breast Milk Production: A Per-Protocol Analysis from the EMPOWER Trial.

BACKGROUND: Galactogogues are often considered when mothers of very preterm infants experience challenges in producing adequate amounts of breast milk. We conducted a per-protocol analysis of those mothers who completed a 14-day course of domperidone during the EMPOWER trial. Our primary aim was to evaluate the response to a completed course of domperidone and whether the response was affected by the timing of the initiation of intervention. METHODS: For this analysis, 83 mothers of infants ≤29 weeks gestation were included: 45 mothers who received domperidone from days 1 to 14 of the trial study treatment period and 38 mothers who received domperidone from days 15 to 28. Domperidone was given at a dose of 10 mg thrice daily for 14 days. The primary outcome was the proportion of mothers who achieved a modest 50% increase in breast milk volume from the volume at the end of the 2-week period of treatment of domperidone. RESULTS: When adjusted for the initiation of domperidone treatment, the proportion of mothers in the days 1-14 group (77.8%) was similar compared to those in the days 15-28 group (65.8%), OR 1.96 (95% CI 0.72-5.32; p = 0.19). CONCLUSION: Taking into consideration potential limitations in power, this secondary analysis was able to show that the mothers in the EMPOWER study who were identified as actually completing a 14-day treatment course responded irrespective of the timing of their initiation of domperidone and demonstrated a modest increase in breast milk volume.

Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of ß-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells.

Efficacy of Chinese herbal medicine Zengru Gao to promote breastfeeding: a multicenter randomized controlled trial.

BACKGROUND: Breastfeeding is recommended worldwide but not fully practiced. The first week after childbirth is regarded as a critical period for increasing breast milk production. The aim of the study was to investigate whether Chinese herbal medicine Zengru Gao would result in more women breastfeeding in the first week after childbirth. METHODS: A multicenter randomized controlled trial was conducted of 588 mothers considering breastfeeding in China. Among the mothers of the intervention group, the intervention included Chinese herbal medicine Zengru Gao; among those of the control group, it did not. Primary outcomes were the percentages of fully and partially breastfeeding mothers. Secondary outcome was baby's daily formula intake. RESULTS: At 3 d and 7 d after delivery, significant differences were found in favour of Zengru Gao group on the percentage of full/ partial breastfeeding (Z = - 3.0037, p = 0.0027). At day 7, the percentage of full/ partial breastfeeding of the active group increased to 71.48%/20.70% versus 58.67%/30.26% in the control group, the differences remained significant (Z = - 3.0037, p = 0.0027). No statistically significant differences were detected on primary measures at 1 d. While intake of formula differed between groups at 1 d and 3 d, this difference did not achieve statistical significance, but this difference was apparent by 7 d (55.45 ± 115.39 ml/day vs 90.66 ± 153.89 ml/day). CONCLUSION: In conclusion, Chinese Herbal medicine Zengru Gao enhanced breastfeeding success during one week postpartum. The approach is acceptable to participants and merits further evaluation. TRIAL REGISTRATION: ChiCTR-IPR-15007376 , December 11, 2015.

Case report: domperidone use as a galactagogue resulting in withdrawal symptoms upon discontinuation.

We present a case of domperidone withdrawal in a woman using the medication as a galactagogue. Our primary goal is to increase the literature available to providers who work with women who are breastfeeding. We evaluated a woman presenting to our reproductive psychiatry clinic for consultation regarding anxiety and agitation in the context of domperidone discontinuation. We evaluated the available literature regarding domperidone as a galactagogue, as well as the literature regarding adverse effects. The patient presented with withdrawal symptoms after gradual taper and discontinuation of domperidone. After restarting the medication, her symptoms resolved. She was able to successfully discontinue domperidone with a slow, gradual taper. Domperidone is occasionally used as a galactagogue in women with inadequate milk supply. We report a case in which a woman experienced withdrawal symptoms after domperidone discontinuation.

Postpartum Lactation-Mediated Behavioral Outcomes and Drug Responses in a Spontaneous Mouse Model of Obsessive-Compulsive Disorder.

Using a spontaneous mouse model of obsessive-compulsive disorder (OCD), the current study evaluated the influence of postpartum lactation on the expression of compulsive-like behaviors, SSRI effectiveness, and the putative role of oxytocin and dopamine in mediating these lactation specific behavioral outcomes. Compulsive-like lactating mice were less compulsive-like in nest building and marble burying and showed enhanced responsiveness to fluoxetine (50 mg/kg) in comparison to compulsive-like nonlactating and nulliparous females. Lactating mice exhibited more anxiety-like behavior in the open field test compared to the nulliparous females, while chronic fluoxetine reduced anxiety-like behaviors. Blocking the oxytocin receptor with L368-899 (5 mg/kg) in the lactating mice exacerbated the compulsive-like and depression-like behaviors. The dopamine D2 receptor (D2R) agonist bromocriptine (10 mg/kg) suppressed marble burying, nest building, and central entries in the open field, but because it also suppressed overall locomotion in the open field, activation of the D2R receptor may have inhibited overall activity nonspecifically. Lactation- and fluoxetine-mediated behavioral outcomes in compulsive-like mice, therefore, appear to be partly regulated by oxytocinergic mechanisms. Serotonin immunoreactivity and serum levels were higher in lactating compulsive-like mice compared to nonlactating and nulliparous compulsive-like females. Together, these results suggest behavioral modulation, serotonergic alterations, and changes in SSRI effectiveness during lactation in compulsive-like mice. This warrants further investigation of postpartum events in OCD patients.

After Chemotherapy Treatment for Maternal Cancer During Pregnancy, Is Breastfeeding Possible?

OBJECTIVE: To report breastfeeding complaints of women diagnosed with cancer during pregnancy and correlate success with characteristics of their treatment. MATERIALS AND METHODS: This is a prospective cohort study of women diagnosed with cancer during pregnancy who attempted breastfeeding. We surveyed participants about breast engorgement, milk let down, and consistent breast milk production through mailed questionnaires. Treatment details, including the type and number of chemotherapy cycles given during pregnancy and antepartum or postpartum depression, were collected. A single pathologist evaluated surgical specimens to note lactational changes while blinded to patient's treatment. The primary endpoint was successful breastfeeding without reporting any lack of or decreased breast milk production. RESULTS: When comparing women who underwent chemotherapy during pregnancy to women who did not, there was a significant difference in reporting a lack of or a perceived decrease in breast milk supply and the need to provide supplemental feeding to their infants (63.5% and 9%, respectively, p < 0.001). In the women who received chemotherapy, there was no significant difference in maternal age, cancer type, or stage with regard to breastfeeding difficulties. Gestational age at the first cycle and the number of cycles were significant factors associated with breastfeeding difficulties (p = 0.006 and p = 0.0003, respectively). Antepartum and postpartum depression was not associated with decreased breast milk production. A lack of lactational changes and significant lobular atrophy were noted in the women given neoadjuvant chemotherapy. CONCLUSION: Women who undergo chemotherapy during a pregnancy are more likely to report breastfeeding difficulties.

Progesterone-Containing Gel Does Not Eliminate Postpartum Breast Engorgement?

BACKGROUND: Severe breast engorgement can cause substantial discomfort for mothers and interfere with an infant's ability to feed at the breast. The aim of the study was to clarify the possibility that the percutaneous progesterone-containing gel (Progestogel) can eliminate severe postpartum breast engorgement in lactating women. SUBJECTS AND METHODS: Twenty three patients were examined. The Progestogel for transdermal therapy in an amount of 2.5-3 g was applied to the breast. Before application and 20 min after application the density of the mammary glands was measured by a tonometer. RESULTS: According to our observations, within 20 min application of 2.5-3 g of the Progestogel on the breast skin does not result in reducing breast swelling, engorgement and tenderness. CONCLUSIONS: After 20 minutes, transdermal application of Progestogel does not reduce the degree of engorgement of the mammary glands in the postpartum period.

Domperidone for Treatment of Low Milk Supply in Breast Pump-Dependent Mothers of Hospitalized Premature Infants: A Clinical Protocol.

Mothers of hospitalized premature infants who choose to provide breast milk are at increased risk of an inadequate breast milk supply. When nonpharmacologic interventions to increase milk supply fail, clinicians are faced with limited options. There is no current evidence to support the use of herbal galactogogues in this population and a black box warning for metoclopramide for potential serious side effects. Thus, domperidone was the only known, effective option for treatment of low milk supply in this population. With a thorough review of the literature on domperidone and coordination with the obstetrical, neonatal, lactation, and pharmacology teams, a domperidone treatment protocol for mothers of hospitalized premature infants with insufficient milk supply was developed at our institution and is presented in this article. A comprehensive understanding of domperidone for use as a galactogogue with a standard treatment protocol will facilitate safer prescribing practices and minimize potential adverse reactions in mothers and their hospitalized premature infants.

Evaluation of the galactogogue effect of silymarin on mothers of preterm newborns (<32 weeks).

Hypogalactia has a relative high frequency in women having delivered preterm infants, who often have difficulties in maintaining a sufficient production of milk for their infants' needs over prolonged periods of time. Recent studies have shown a potential galactogogue effect of silymarin on milk production in animal models (cows and rats) and in humans (mothers of term newborns); nonetheless, none of the studies conducted on humans consisted of double-blind randomized clinical trials and no data are available concerning mothers who delivered preterm infants. The aim of our study was to assess the efficacy of silymarin (BIO-C®) as galactogogue and its tolerability in mothers who delivered preterm infants. We enrolled 50 mothers at 10±1 days post-partum who had delivered infants at ® and placebo arms. No adverse events were observed in the 2 arms among mothers and infants, and silymarin and its metabolites were not detectable in the analyzed human milk samples. Further investigation on specific patient groups affected by hypogalactia, defined according to stricter criteria, should be planned to assess the efficacy of the product in increasing milk production.

[Breast-feeding (part II): Lactation inhibition--Guidelines for clinical practice]. / Allaitement maternel (partie II): méthodes d'inhibition de la lactation--recommandations pour la pratique clinique.

OBJECTIVE: Provide guidelines for clinical use of non-pharmacological and pharmacological treatments of inhibition of lactation and the management of the weaning. MATERIALS AND METHODS: Systematically review of the literature between 1972 and May 2015 from the databases Medline, Google Scholar, Cochrane Library, and the international recommendations about inhibition of lactation with establishment of levels of evidence (LE) and grades of recommendation. RESULTS: The available data on the effectiveness of non-pharmacological measures are limited, with very low levels of evidence that fail to make recommendations (Professional consensus). Pharmacological treatments for inhibition of lactation should not be given routinely to women who do not wish to breast-feed (Professional consensus). For women aware of the risks of pharmacological treatments of inhibition of lactation, lisuride and cabergolin are the preferred drugs (Professional consensus). Because of potentially serious adverse effects, bromocriptin is contraindicated in inhibiting lactation (Professional consensus). Available data on management of lactation weaning fail to provide recommendation and no treatment is recommended (Professional consensus). CONCLUSION: Bromocriptin is contraindicated in the treatment of inhibiting lactation. Women who do not wish to breast-feed have to be informed of the benefits and disadvantages of the pharmacological treatment for inhibition of lactation.

[Pharmaceutical treatment of lactation deficiency lacks evidence]. / Manglende evidens for medicinsk behandling af ammeinsufficiens.

In this review we have looked at the evidence for the pharmacological treatment of lactation deficiency. Five RCTs (n = 166) of metoclopramide found no effect on lactation and two RCTs (n = 26) of older date and lesser quality found significant effect. One RCT (n = 51) of syntocinon found no effect on lactation and two older RCTs (n = 60) of lesser quality found significant effect. Three RCTs (n = 105) found significant effect of domperidone on lactation. Education on breastfeeding is important to avoid the need for pharmacological treatment.

Complementary, holistic, and integrative medicine: advice for clinicians on herbs and breastfeeding.

The use of herbal remedies is a tradition held in many cultures throughout the world, and women may use herbal remedies during lactation. Because of the limitations of the current literature, it is difficult to develop accurate information on the safety and efficacy of specific herbs used during breastfeeding. It is critical that more research is conducted in this area, including national prevalence studies and safety and efficacy studies.

[Cure rates of chronic subclinical Staphylococcus aureus mastitis in lactating dairy cows after antibiotic therapy]. / Heilungsraten chronischer subklinischer Staphylococcus aureus-Mastitiden nach antibiotischer Therapie bei laktierenden Milchkühen.

Staphylococcus (S.) aureus is an important mastitis causing pathogen in dairy cows worldwide. The aim of this controlled and randomized study was to analyze the effects of an antibiotic treatment on chronic subclinical S.aureus mastitis during lactation.The study was conducted between July 2011 and December 2011 in Northern Germany including 134 udder quarters (i. e. 103 dairy cows) infected with S. aureus. The animals were randomly divided into two groups (control and treatment group). Quarter foremilk duplicate samples were taken on days 0, 7, 32 and 39 from each infected udder quarter for microbiological analysis and somatic cell count determination. Treatment consisted of cephalexin (200 mg intramammarily 5 times every 12 h) plus marbofloxacine (2 mg/kg BM subcutaneously 3 times every 24 h). "Pathogen elimination" was assessed as the status, when no S. aureus was isolated from the quarter samples of days 32 and 39. "Cure" was defined as the status, when in addition to pathogen elimination the somatic cell count of the quarter in both milk samples was below 100 000/ml. Animals of the treatment group showed a pathogen elimination rate of 35.9% and a cure rate of 21.9%. The rates for the control group were 21.4% and 8.6%, resp. The differences between groups were statistically significant. These results indicate that pathogen elimination and cure rates of chronic subclinical S. aureus mastitis are low after an intramammary cephalexin and subcutaneous marbofloxacine treatment, but still significantly better than without any antibiotic treatment.