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.

Inflammatory markers before and after farrowing in healthy sows and in sows affected with postpartum dysgalactia syndrome.

BACKGROUND: The pathogenesis of postpartum dysgalactia syndrome (PDS) in sows is not fully elucidated and affected sows often present vague clinical signs. Accurate and timely diagnosis is difficult, and PDS is often recognized with a delay once piglets begin to starve. Increased rectal temperature of the sow is an important diagnostic parameter, but it may also be influenced by a number of other parameters and is thus difficult to interpret. Inflammatory markers may be important adjuncts to the clinical assessment of sows with PDS, but such markers have only been studied to a limited extent. The objective was to characterize the inflammatory response in healthy sows and in sows suffering from PDS, and to identify biomarkers that may assist in early identification of PDS-affected sows. RESULTS: Thirty-eight PDS-affected (PDS+) and 38 healthy (PDS-) sows underwent clinical examination and blood sampling every 24 h, from 60 h before the first piglet was born to 36 h after parturition. In both groups, inflammatory markers changed in relation to parturition. Most inflammatory markers changed 12-36 h after parturition [white blood cell counts (WBC), neutrophil counts, lymphocyte counts, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin (Hp), iron (Fe) and albumin (ALB)]. Changes in neutrophil counts, lymphocyte counts, CRP, Fe and ALB were observed -12 to 0 h before parturition. WBC, neutrophil and lymphocyte counts, serum concentrations of TNF-α, IL-6, Hp and Fe differed between PDS+ and PDS- sows. These differences were mainly apparent 12 to 36 h after parturition, but already at 12 h before parturition, PDS+ sows had lower lymphocyte counts than PDS- sows. CONCLUSIONS: Parturition itself caused significant inflammatory changes, but PDS+ sows showed a more severe response than PDS- sows. WBC, neutrophil and lymphocyte counts, and concentrations of TNF-α, IL-6, Hp and Fe can be potential biomarkers for PDS. Lymphocyte counts may be used to detect PDS at pre-partum. To assess their diagnostic potential, these markers must be investigated further and most likely combined with assessment of clinical parameters and other biomarkers for improved identification of sows at risk of developing PDS.

Selected serum acute-phase proteins in peripartum sows and evaluation of their diagnostic usefulness.

Lactation impairment in sows is a frequent and significant clinical problem. Due to a complex aetiopathogenesis, early diagnosis of postpartum dysgalactia syndrome (PDS) is difficult and so far has usually been based on physical examination performed in the first days after farrowing. To date no data have been provided on the diagnostic usefulness of acute phase proteins (APP) in early diagnosis of peripartum disorders, including lactation disorders in sows. This study aimed at measuring the serum concentration of selected APP (C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP)) in sows with physiological and pathological course of the peripartum period and at evaluating the possibility of utilising the studied markers in the early diagnosis of lactation disorders. Also, the correlation between the studied APP serum concentration and production parameters was assessed. To the best of the authors' knowledge, the present study is the first such performed on sows. The experiment was conducted on 139 sows divided into three experimental groups based on the course of peripartum period: HEALTHY (n = 58) - clinically healthy sows, PDS (n = 45) - sows with milk production disorders, and OTHERS (n = 36) - sows which had experienced difficult parturitions, inflammations not connected with mammary glands (abscesses, hooves infections), or lameness. Thirteen serum samples from each sow were analysed, samples being taken on days -28 (-30 to -25), -14 (-16 to -11), -7 (-8 to -6), -5, -3, -1, 0 (parturition day), +1, +3, +5, +7, +14 and +28 (prior to or post farrowing). In order to measure the level of serum APP, commercial, quantitative ELISA tests were used. The results of the study indicate that the diagnosis made on the basis of the assessment of SAA levels on day 7 before the farrowing was not statistically different from the diagnosis made on the basis of the physical examination in the first days after the farrowing, that is the so-called "gold standard". The achieved results indicate that SAA may be a useful early marker of lactation impairments in sows, which allows detection of which sows are susceptible to lactation disorders with high probability even as early as one week before parturition.

Delayed diagnosis of Sheehan's syndrome in a developed country: a retrospective cohort study.

BACKGROUND: Little is known about Sheehan's syndrome (SS), even though it is believed that its incidence is low. The aims of this study were to determine the clinical features and diagnostic delay of SS and to ascertain whether early signs could have allowed earlier diagnosis. SUBJECTS AND METHODS: All patients with SS diagnosed in reference units in the southeast of France between 1980 and 2011 were recruited for this study. Data on obstetrical history, clinical symptoms suggestive of hypopituitarism, early signs, hormone analysis, and magnetic resonance imaging were collected. RESULTS: Of the 40 women found to have SS, 39 were studied. Mean delay in the diagnosis of SS was 9 ± 9.7 years. We found that four of the 35 assessable patients were diagnosed with agalactia, 16 of the 29 assessable ones with amenorrhea, 19 of the 39 with hypothyroidism, eight with acute adrenal insufficiency, and 15 with asthenia. Among the patients for whom there was a diagnostic delay of more than 1 year (n=28), seven had headaches during the postpartum period, all assessable patients had agalactia, six of the 22 assessable ones had amenorrhea, seven of 28 had hypothyroidism, and 12 of 28 had asthenia. CONCLUSION: Most signs of SS are aspecific and classical signs such as agalactia and amenorrhea are often difficult to detect, which can explain the long diagnostic delay. We suggest that all women failing to lactate after postpartum hemorrhage (PPH) should be evaluated by measuring prolactin levels and women with signs such as amenorrhea and asthenia, even several years after PPH, should undergo a blood test including assessment of thyroxine, TSH, 0800  h ACTH-cortisol, and IGF1 levels.

Short communication: Circulating serotonin (5-HT) concentrations on day 1 of lactation as a potential predictor of transition-related disorders.

The monoamine serotonin (5-hydroxytryptamine; 5-HT) has been described as a homeostatic regulator of lactation. Recently, our laboratory determined that 5-HT is involved in the regulation of calcium and glucose homeostasis during the transition period in rodents. More specifically, we demonstrate that 5-HT is responsible for calcium mobilization from bone and upregulation of hepatic gluconeogenic enzymes and mammary gland glucose transporters. Our objective was to investigate the correlation between circulating 5-HT concentrations and circulating ionized calcium, parathyroid hormone-related protein (PTHrP), and glucose concentrations on d 1 postpartum. We also investigated the correlation between circulating 5-HT and milk fever and ketosis incidence and severity in multiparous Holstein cows at the onset of lactation. Blood samples were collected from 42 multiparous cows on d 1 of lactation and analyzed for 5-HT, calcium, glucose, and PTHrP. Milk fever (determined subjectively for each cow on d 1 postpartum) and ketosis incidence and severity (scale 1 to 4, determined objectively for each cow during the first 10 d postpartum) were recorded for all animals. Serum 5-HT was positively correlated with serum calcium and with plasma PTHrP (r>0.37). Serum 5-HT was negatively correlated with milk fever incidence and with ketosis severity (most severe ketosis incidence recorded during the first 10 d postpartum; r<-0.33). Serum calcium and plasma glucose concentrations were negatively correlated with milk fever and ketosis severity, respectively (r<-0.39). These data indicate that 5-HT potentially plays a role in the regulation of calcium and glucose homeostasis during the transition period in cattle, which we previously demonstrated in rodents. Increased circulating concentrations of 5-HT might decrease milk fever at the onset of lactation and ketosis severity during the first 10 d postpartum in dairy cows. Understanding this physiological axis could help describe the underlying mechanisms associated with these periparturient metabolic disorders in dairy cows.

Rusty pipe syndrome: counselling a key intervention.

Presence of blood in the breastmilk renders a rusty or brownish colour to it; this entity is known as "rusty pipe syndrome". Although this is a self-limiting condition, it can be particularly intimidating for mothers and may act as a psychological barrier to successful breastfeeding. We describe this entity in two mothers who had spontaneous blood-stained breastmilk from both breasts in the early post-partum period and were worried about feeding their infants. Subsequent to proper counselling with the use of skills like active listening, accepting their concerns, building confidence by providing relevant information in simple language and by giving suggestions and avoiding commands, both mothers were able to successfully breastfeed their offspring.

Effects of recombinant human prolactin on breast milk composition.

OBJECTIVE: The objective of this study was to determine the impact of recombinant human prolactin (r-hPRL) on the nutritional and immunologic composition of breast milk. METHODS: We conducted 2 trials of r-hPRL treatment. In the first study, mothers with documented prolactin deficiency were given r-hPRL every 12 hours in a 28-day, open-label trial. In the second study, mothers with lactation insufficiency that developed while they were pumping breast milk for their preterm infants were given r-hPRL daily in a 7-day, double-blind, placebo-controlled trial. Breast milk characteristics were compared before and during 7 days of treatment. RESULTS: Among subjects treated with r-hPRL (N = 11), milk volumes (73 ± 36 to 146 ± 54 mL/day; P < .001) and milk lactose levels (155 ± 15 to 184 ± 8 mmol/L; P = .01) increased, whereas milk sodium levels decreased (12.1 ± 2.0 to 8.3 ± 0.5 mmol/L; P = .02). Milk calcium levels increased in subjects treated with r-hPRL twice daily (2.8 ± 0.6 to 5.0 ± 0.9 mmol/L; P = .03). Total neutral (1.5 ± 0.3 to 2.5 ± 0.4 g/L; P = .04) and acidic (33 ± 4 to 60 ± 6 mg/L; P = .02) oligosaccharide levels increased in r-hPRL-treated subjects, whereas total daily milk immunoglobulin A secretion was unchanged. CONCLUSIONS: r-hPRL treatment increased milk volume and induced changes in milk composition similar to those that occur during normal lactogenesis. r-hPRL also increased antimicrobially active oligosaccharide concentrations. These effects were achieved for women with both prolactin deficiency and lactation insufficiency.

Clinical observation on the treatment of post-cesarean hypogalactia by auricular points sticking-pressing.

OBJECTIVE: To explore the effect of auricular points sticking-pressing (APSP) in treating post-cesarean hypogalactia (PCH). METHODS: A randomized, controlled, single-blinded clinical trial on 116 patients with PCH was carried out. They were equally assigned to the treatment group and the control group. The treatment group received APSP, with the pellets pressed for 4 times daily, while the control group was only asked to do lactation to meet infant demand. The therapeutic efficacy and the changes in scores of traditional Chinese medicine (TCM) syndrome, volume of milk secretion, supplementary feeding and serum level of prolactin (PRL) in the two groups were estimated and compared after the patients had been treated for 5 days. RESULTS: The cured and markedly effective rate in the treatment group was 89.7%, which was significantly higher than that in the control group (27.6%, P<0.05), 95% CI (0.1543, 0.2527). The improvement of TCM syndrome, elevation of milking volume, decrease of the supplementary feeding and increase of PRL level revealed in the treatment group were all superior to those in the control group, showing statistical significance (P<0.01). CONCLUSION: APSP shows an apparent efficacy in treating PCH and is worthy of application in clinical practice.

Association of serum prolactin and oxytocin with milk production in mothers of preterm and term infants.

The present study was designed to compare milk production and hormone responses (prolactin [PRL], oxytocin [OT]) and to determine associations of hormone levels with milk production in mothers of preterm (PT) and term (TM) infants during the first 6 weeks postpartum. Mothers of PT infants (n = 95) were all pump dependent; mothers of TM infants (n = 98) were all feeding their infant at breast. Mothers of nonnursing PT infants produced less milk over time compared to mothers of TM infants. A higher proportion of PT mothers had lower basal PRL levels compared with TM mothers. PRL and frequency of breast stimulation combined positively influenced milk production in PT mothers. OT levels were higher in PT versus TM mothers, but OT was not related to milk production. Further study is warranted regarding interventions to enhance milk production, particularly in pump-dependent mothers of PT infants.

[Effects of Maidang Rutong granule on l-dopa-induced galactozemia in rats].

OBJECTIVE: To study galactagogue effect of Maidang Rutong granule on the lactation rats. METHOD: The experiments were designed to observe the efficiency of Maidang Rutong granule on lactescence, serum prolactin, and morphology of mammary gland with rat galactozemia model established by injecting l-dopa. RESULT: Maidang Rutong granule showed significant enhancement for lactescence and the offspring's body weight. It could antagonize the decrease of serum prolactin and the atrophy of mammary gland induced by l-dopa. CONCLUSION: Maidang Rutong granule exhibited significant galactagogue effect on the l-dopa-induced galactozemia in rats.

[Multicentral randomized controlled studies on acupuncture at Shaoze (SI 1) for treatment of postpartum hypolactation].

OBJECTIVE: To explore effect of acupuncture at Shaoze (SI 1) for treatment of postpartum hypolactation. METHODS: Multicentral randomized controlled and single blind clinical trial was adopted, and 276 cases were divided into a treatment group and a control group, 138 cases in each group. The treatment group were treated with electroacupuncture (EA) at Shaoze (SI 1) and the control group with EA at Shangyang (LI 1). After treatment of 2 courses, the therapeutic effects and changes of cumulative score of TCM symptoms, mammary filling degree, lactation amount, prolactin level were evaluated and investigated. RESULTS: The cured and markedly effective rate was 97.8% in the treatment group and 24.3% in the control group with a significant difference between the two groups (P < 0.05). The treatment group in improvement of the cumulative score of TCM symptoms and the mammary filling degree, and increasing the lactation amount and the prolactin level were better than the control group (P < 0.01). CONCLUSION: Acupuncture at Shaoze (SI 1) has obvious therapeutic effect on hypolactation.

Delayed lactogenesis II: a comparison of four cases.

Lactogenesis II is the onset of copious milk production (i.e., the milk "coming in"), which usually occurs between 30 to 40 hours postpartum. When lactogenesis II fails to occur or is delayed, it may be due to a number of underlying hormonal or non-hormonal conditions. Of the various hormonal etiologies, many can be identified with the aid of a few standard blood tests. Gestational ovarian theca lutein cysts may cause delayed lactogenesis II and are fairly easily detected by ordering testosterone levels. Although this condition can delay lactogenesis II for as long as 31 days, with proper management women affected by these cysts have established breastfeeding. Three of the four women reviewed in this article were eventually able to produce 100% of their infants' caloric requirements.

Stress during labor and delivery is associated with delayed onset of lactation among urban Guatemalan women.

A delayed onset of lactation (OL) is likely to have a negative influence on breast-feeding outcomes. Thus, it is important to identify risk factors for delayed OL. We examined prospectively the association between stress during labor and delivery and OL in a cohort of urban Guatemalan women. Healthy women (n = 136) were recruited during the first stage of labor in the labor unit of a social security hospital in Guatemala City. Women provided salivary samples for cortisol determinations 3.2 +/- 3.2 h before birth and 1.7 +/- 1.9 h and 17.1 +/- 4.7 h after delivery. At the same time points women were asked to respond to a 17-item psychosocial stress and anxiety questionnaire. Women were called daily until OL occurred. Primiparous women had higher antepartum and early postpartum cortisol levels that were twice as high as those among multiparous women (P < 0.05). The parity differential in salivary cortisol concentrations vanished with time. General linear model multivariate analysis indicate that multiparous women (n = 77), irrespective of mode of delivery, had an earlier OL (P < 0.05) than primiparae who underwent emergency cesarean section deliveries (n = 11) (adjusted mean +/- SEM, 2.5 +/- 0.1 vs. 3.4 +/- 0.3 d postpartum, respectively). OL took longer to occur among multiparous women with prenatal salivary cortisol levels above (vs. below) the 40th percentile [3 +/- 0.2 (n = 28) vs. 2.4 +/- 0.2 d postpartum (n = 38), respectively; P = 0.02]. Thus, stress during labor and/or delivery is likely to be a significant risk factor for delayed OL in urban Guatemala.

Breastfeeding anaphylaxis case study.

This case describes a woman who experienced an anaphylatic reaction associated with breastfeeding. The reaction occurred with each feeding on day three postpartum and resolved on day four. Possible reasons for this severe reaction are suggested.

Determinants and utility of the anion gap in predicting hyperlactatemia in cattle.

The objectives of this study were to investigate the determinants of the anion gap (AG) in cattle and to evaluate the utility of AG in detecting hyperlactatemia in sick neonatal calves and adult cattle. The AG was calculated as AG = ([Na+] + [K+])-([Cl-] + [HCO-3]), with all values in mEq/L. The AG of healthy neonatal calves (n = 16) was 29.6 +/- 6.2 mEq/L (mean +/- SD), and the blood L-lactate concentration ranged from 0.5 to 1.2 mM/L. The AG was significantly (P < .05) correlated with serum phosphate (r = .66) and creatinine (r = .51) concentrations. The AG of neonatal calves with experimentally induced diarrhea (n = 16) was 28.6 +/- 5.6 mEq/L, and the blood L-lactate concentration ranged from 1.1 to 2.9 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .67), serum phosphate concentration (r = .63), creatinine concentration (r = .76), and blood pH (r = -.61). The AG of adult cattle with abomasal volvulus (n = 41) was 20.5 +/- 7.8 mEq/L, and the blood L-lactate concentration ranged from 0.6 to 15.6 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .60), serum phosphate concentration (r = .71), creatinine concentration (r = .65), albumin concentration (r = .47), total protein concentration (r = .54), blood pyruvate concentration (r = .67), and blood pH (r = -.41) but not plasma beta-OH butyrate concentration. The results indicate that the AG in cattle is only moderately correlated with blood L-lactate concentration and is similarly correlated with serum phosphate and creatinine concentrations in neonatal calves and adult cattle, as well as with serum albumin and total protein concentrations in adult cattle. Anion gap determination is of limited usefulness in predicting blood L-lactate concentration in sick cattle, whereas the correlation between AG and serum creatinine concentration in sick cattle suggests that an increased AG should alert the clinician to the potential presence of uremic anions.

Growth hormone increases breast milk volumes in mothers of preterm infants.

AIMS: To determine the galactopoietic response to recombinant human growth hormone (hGH) in mothers of premature infants with inadequate lactation. STUDY DESIGN: Prospective placebo-controlled, double-blind trial. SUBJECTS: Twenty healthy mothers on no concurrent medication, with infants born between 26 and 34 weeks' gestation with insufficient milk production for their infants' needs. INTERVENTIONS: Ten mothers received hGH, .2 IU/kg/day subcutaneously to a maximum of 16 IU/day, for 7 days, while 10 mothers received the same volume of placebo. One mother from each group withdrew from the study. OUTCOME MEASURES: Maternal milk production and plasma concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and growth hormone (GH) were determined before starting treatment and 1 day after stopping therapy. A nurse measured the amount of milk expressed (5 to 6 times daily) plus, if the infant was suckling, weighed the infant before and after feeding. RESULTS: The mothers were enrolled 35 +/- 26 days after birth; at this time the infants weighed 1.89 +/- .64 kg. Milk production in hGH-treated mothers increased from 139 +/- 49 mL/day to 175 +/- 46 mL/day after 7 days of treatment (a rise of 31%). Placebo-treated mothers showed no significant change from 93 +/- 50 mL/day to 102 +/- 69 mL/day (a rise of 7.6%, not significant). Milk production increased in all treated mothers but decreased in 4 of 9 placebo mothers. Plasma concentrations of IGF-1 and IGFBP-3 increased in hGH-treated mothers but not placebo-treated mothers; there was no change in plasma GH levels in either group. No adverse effects were seen with hGH treatment in the mothers or infants. CONCLUSIONS: hGH therapy in mothers with lactational insufficiency can improve breast milk volumes.

[Clinical and experimental study of yangxueshengru oral liquor in promoting puerperal breast milk secretion].

Applying Yangxueshengru Oral Liquor (YXSR) to treat 103 cases of puerperal insufficient lactation. Six hours after delivery, the parturient took YXSR, its effective rate was 98.06%. The results revealed that it could improve breast milk secretion significantly and increase daily lactation amount of parturient, insufficient lactation rate was reduced. The content of protein and trace elements (Fe, Zn and Mn, etc) in colostrum increased, the difference between medicated group and control group was significant (P < 0.05-0.001). Animal experiment showed that YXSR could increase the response of prolactin (PRL) level of model rats (P < 0.01), the serum, PRL and cortisol level of the rats were also raised significantly (P < 0.01).