Impact of Surfactant Protein-A on Immunomodulatory Properties of Murine and Human Breast Milk.

OBJECTIVES: Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk's immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice. METHODS: Human milk was collected at postpartum days 1-3 and 28. Mouse milk was collected at postpartum days 1-10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR. RESULTS: SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1ß, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams. CONCLUSIONS: SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.

Hydroxyurea Exposure in Lactation: a Pharmacokinetics Study (HELPS).

Lactation is contraindicated for women with sickle cell anemia receiving hydroxyurea therapy, despite sparse pharmacokinetics data. In 16 women who were lactating volunteers, we documented hydroxyurea transferred into breastmilk with a relative infant dosage of 3.4%, which is below the recommended 5%-10% safety threshold. Breastfeeding should be permitted for women taking daily oral hydroxyurea.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use. OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification. MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome. AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

Cannabis Use During Lactation: Literature Review and Clinical Recommendations.

Cannabis is the most commonly used psychoactive substance in Canada. The prevalence of cannabis use both during pregnancy and in the postpartum period has been estimated at 5% of the population. Women who use the drug during lactation place their infants at risk of exposure to cannabis and its metabolites in breast milk. This article provides a systematic review of infant outcomes associated with cannabis use by women during lactation followed by clinical recommendations. A review of the literature was conducted using Medline, Embase, and PsychInfo from their start to July 2018. Inclusion criteria consisted of articles addressing the impact of postpartum cannabis use by lactating women and providing developmental outcomes for infants. Two articles met these criteria and were included in our systematic review. Results indicate conflicting outcomes regarding the risk of exposure to cannabis in breast milk. Women should be advised to abstain from cannabis use during lactation or reduce consumption if abstinence is not possible. Furthermore, women should be advised to avoid breastfeeding within 1 hour of inhaled use to reduce exposure to highest concentration of cannabis in breast milk. Despite some evidence regarding health risks of post-natal exposure to cannabis, further research is needed to determine its impact on infant neurodevelopmental outcomes beyond the first year of life.

Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety.

Nicotinamide is a water-soluble vitamin B3 derivative that has many roles in medicine. This review examines the role of nicotinamide in dermatology and its actions in preventing photoageing and skin cancers in humans. Nicotinamide prevents ultraviolet radiation (UV) from reducing ATP levels and inhibiting glycolysis, thus preventing the UV radiation-induced energy crisis. This enhances DNA repair and reduces UV-induced suppression of immunity. Randomised controlled clinical trials have also shown that nicotinamide reduces transepidermal water loss and the development of new non-melanoma skin cancers in high-risk humans. This review also examines nicotinamide's safety profile.

Valproic acid concentrations in nursing mothers, mature milk, and breastfed infants in monotherapy and combination therapy.

Valproic acid (VPA) is currently one of the four most often prescribed antiepileptic drugs (AEDs) in pregnancy. However, only a small number of studies have measured suckling infant serum levels of the drug. We studied the transport of VPA from breastfeeding mothers to the mature milk and breastfed infants and the influence of comedication with enzyme-inducing AEDs. The data of 30 nursing women treated by VPA were analyzed retrospectively. Mature milk, maternal, and infant serum levels were collected between the 6th and 32nd postnatal day and measured by gas chromatography during the years 1996-2017. Valproic acid levels varied from 5.4 to 69.0 mg/L (mean: 39.0 ±â€¯16.1 mg/L) in the maternal serum, from <1.0 to 16.7 mg/L (mean: 1.6 ±â€¯3.9 mg/L) in the milk, and from <1.0 to 17.5 mg/L (mean: 4.2 ±â€¯4.3 mg/L) in the infant serum. The milk/maternal serum level ratio ranged from <0.03 to 0.25 (mean: 0.03 ±â€¯0.06) and the infant/maternal serum level ratio from <0.03 to 0.61 (mean: 0.11 ±â€¯0.13). Sixty-seven percent of milk and 33% of infant VPA concentrations were below the limit of quantification. No correlations were observed between maternal serum and milk levels or between maternal and infant serum levels. In conclusion, none of the milk or infant serum VPA levels reached the lower limit of the reference range used for the general population with epilepsy, so the degree of VPA exposure in breastfed infants is less than during gestation. Nevertheless, if signs of potential adverse reactions manifest, infant serum concentrations should be measured.

Postpartum hormonal contraception in breastfeeding women.

PURPOSE OF REVIEW: To provide an overview of recent research and guidelines regarding contraception and breastfeeding. RECENT FINDINGS: Recent studies assessed lactogenesis, breastfeeding rates, and milk supply concerns in patients starting postpartum hormonal contraception. One study showed a small but statistically significant increase in milk supply concerns between users and nonusers of postpartum hormonal contraception. Mean time to lactogenesis and breastfeeding rates were similar between patients with immediate and delayed insertion of the levonorgestrel (LNG) implant in one study and the LNG intrauterine device (IUD) in another study. Two studies assessed nursing knowledge and attitudes toward postpartum contraception in breastfeeding women, showing that postpartum nurses had incorrect knowledge of contraceptive safety in this patient population. Both studies demonstrated persistent erroneous beliefs that depot medroxyprogesterone acetate (DMPA) adversely affects breastfeeding. In postpartum patients intending to breastfeed, more than half intended to initiate contraception within 6 weeks postpartum and few indicated effect on breastfeeding as a factor in their decision. SUMMARY: There are no significant differences in lactogenesis, breastfeeding, and infant growth parameters between immediate postpartum (IPP) and delayed insertion of LNG implants and IUDs. Labor and delivery and postpartum nurses have persistent erroneous beliefs that DMPA negatively affects breastfeeding. Patients desire to use contraception postpartum but prenatal counseling rates and practices are of variable content and quality.

Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis.

BACKGROUND: Women with multiple sclerosis (MS) experience an increased risk of relapse in the postpartum period. High-dose methylprednisolone is the first-line treatment for acute relapses. OBJECTIVES: To determine the transfer of methylprednisolone into human milk in breastfeeding MS patients. METHODS: Methylprednisolone therapy was given for postpartum relapse to nine patients for three consecutive days, and seven patients received a daily infusion once a month. Breast milk samples were obtained before infusion and 1, 2, 4, 8, and 12 hours after completion of infusion. RESULTS: Methylprednisolone concentrations in milk were below detection limits immediately before infusion. Cmax was measured at 1, 2, 4, 8, and 12 hours after infusion and levels of 2.100, 1.659, 0.680, 0.174, and 0.102 µg/mL were determined, respectively. The absolute infant dose was 98.98 µg/kg/day, and the relative infant dose (RID) was 0.71% of the weight-adjusted maternal dose. CONCLUSION: The level of methylprednisolone transfer into breast milk is very low. The RID for methylprednisolone was lower than the generally accepted value. As methylprednisolone therapy is of short duration, infant exposure would be very low should a mother choose to breastfeed 1 hour after infusion. Waiting 2-4 hours after infusion will limit infant exposure still further.

Impact of serotonin reuptake inhibitor use on breast milk supply in mothers of preterm infants: a retrospective cohort study.

AIMS: The aims of the present study were to examine the association between late pregnancy exposure to serotonin reuptake inhibitor (SRI) antidepressants and difficulties in achieving an adequate breast milk supply in women who have given birth to preterm infants, while accounting for the potential impacts of underlying maternal psychiatric illness. METHODS: A retrospective cohort study was carried out of 3024 women delivering liveborn preterm infants (<37 weeks' gestation) between January 2004 and December 2008. The primary outcome was postnatal domperidone use, considered to be a valid proxy for the presence and pharmacological management of low milk supply. Relative risks adjusted for maternal sociodemographic characteristics and comorbidities (aRRs) were calculated for low milk supply, comparing women with late pregnancy exposure to SRI antidepressants (n = 86), women with a psychiatric illness but no antidepressant use (n = 126) and women with neither antenatal exposures (n = 2812). RESULTS: Compared with non-exposed women, nonmedicated psychiatric illness [aRR 1.64; 95% confidence interval (CI) 1.16, 2.30] but not late pregnancy SRI use (aRR 1.00; 95% CI 0.59, 1.70) was associated with an increased risk of domperidone use, indicative of low milk supply. CONCLUSIONS: These findings do not support the previously observed negative impacts of antidepressant use on breastfeeding, instead suggesting that women with an underlying psychiatric illness appear at greatest risk of experiencing low milk supply and could benefit from additional breastfeeding education and support.

Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis.

BACKGROUND: Mothers of preterm infants often struggle to produce enough breast milk to meet the nutritional needs of their infant. Galactagogues such as domperidone are often prescribed to increase breast milk supply but evidence supporting their role in clinical practice is uncertain. OBJECTIVE: To evaluate the efficacy and safety of domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants. SEARCH STRATEGY: MEDLINE, Embase and Web of Science were searched without language restrictions from first publication until January 2017. Bibliographies of articles and reviews were hand-searched for additional reports. SELECTION CRITERIA: Randomised controlled trials that compared domperidone with placebo in mothers of preterm infants (<37 weeks' gestation) experiencing insufficient milk supply. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated study quality. Differences in breast milk volume and adverse events were combined using fixed effects meta-analysis. MAIN RESULTS: The pooled analysis of five trials consisting of 194 women demonstrated a moderate increase in daily breast milk volume of 88.3 ml/day (95% CI 56.8-119.8) with the use of domperidone compared with placebo. No difference was evident with respect to maternal adverse events (odds ratio 1.05, 95% CI 0.65-1.71), with no reported cases of prolonged QTc syndrome or sudden cardiac death. Sensitivity analyses showed no important differences in the estimates of effects. CONCLUSIONS: Domperidone is well tolerated and results in a moderate short-term increase in expressed breast milk volume among mothers of preterm infants previously identified as having insufficient breast milk supply. TWEETABLE ABSTRACT: Domperidone leads to short-term improvements in breast milk volume in mothers of preterm infants.

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.

The effects of a lipid-based nutrient supplement and antiretroviral therapy in a randomized controlled trial on iron, copper, and zinc in milk from HIV-infected Malawian mothers and associations with maternal and infant biomarkers.

We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (≤30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal α-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation.

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study.

BACKGROUND: Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. METHODS: CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. RESULTS: 19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. CONCLUSION: When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc--free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. TRIAL REGISTRATION NUMBER: NCT02154425; Results.

Mood stabilizers during breastfeeding: a systematic review of the recent literature.

OBJECTIVE: This review examined the safety of mood stabilizers in exposed breastfed infants. METHODS: PubMed was searched for English language reports between 1 January 1995 and 30 August 2015 by using combinations of key words breastfeeding, lactation, postpartum period, puerperium, mood stabilizers, lithium, lamotrigine, valproate, carbamazepine, and oxcarbazepine. Case reports, case series, and prospective or cross-sectional studies including relevant data such as relative infant dose, milk-to-plasma ratio, infant drug plasma levels, and adverse events were identified. RESULTS: A total of 26 of 604 relevant reports in PubMed were included in the study. These reports included lamotrigine (122 cases in 12 reports), lithium (26 cases in five reports), carbamazepine (64 cases in five reports), valproate (nine cases in three reports), and oxcarbazepine (two cases in two reports). Of 26 reports, one report included both carbamazepine and valproate. The reports suggest that a considerable amount of lithium and lamotrigine are excreted into breast milk. There is a paucity of data on valproate and oxcarbazepine; however, the infant/maternal ratio of serum drug concentration seems to be lower in valproate exposure compared to other mood stabilizers. The incidence of adverse events in infants exposed to mood stabilizers is reported to be very low. CONCLUSIONS: The current data suggest that mood stabilizers can be prescribed without any adverse events in most infants in lactating women. The available reports also suggest a low prevalence rate of laboratory abnormalities including hepatic, kidney, and thyroid functions in the infants. Additional studies examining short-term and especially long-term effects of mood stabilizers on breastfed infants are required.

Combined hormonal versus nonhormonal versus progestin-only contraception in lactation.

BACKGROUND: Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production. OBJECTIVES: To determine the effects of hormonal contraceptives on lactation and infant growth SEARCH METHODS: We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators. SELECTION CRITERIA: We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval. DATA COLLECTION AND ANALYSIS: For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis. MAIN RESULTS: In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information.For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year.For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant.Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS. AUTHORS' CONCLUSIONS: Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.

Lactation and the Substance-Exposed Mother-Infant Dyad.

Pregnant and postpartum women with substance use disorders have very unique needs and can present challenges to healthcare providers who are not familiar with how to evaluate and respond properly to their necessities. One such situation frequently arises when women with substance use disorders wish to breast-feed. There are many benefits and challenges to this practice that are specific to this population, and treating practitioners are often unclear on how to address them. The purpose of this article is to identify barriers to lactation in substance-exposed dyads and to provide strategies to mitigate these barriers and for promoting lactation in appropriate women with substance use disorders who wish to breast-feed.

Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement. therapy.

The authors describe the first mother-infant pair to complete an on-going, prospective, open-label, Phase 4 trial (ALIU) UU3, NCT00418821) determining the safety of laronidase enzyme replacement therapy (ERT) in pregnant women with mucopolysaccharidosis type I (MPS I) and their breastfed infants. The mother, a 32-year-old with attenuated MPS I (Scheie syndrome), received laronidase for three years and continued treatment throughout her second pregnancy and while lactating. A healthy 2.5 kg male was delivered by elective cesarean section at 37 weeks. He was breastfed for three months. No laronidase was detected in breast milk. The infant never developed anti-laronidase IgM antibodies, never had inhibitory antibody activity in a cellular uptake assay, and always had normal urinary glycosaminoglycan (GAG) levels. No drug-related adverse events were reported. At 2.5 years of age, the boy is healthy with normal growth and development. In this first prospectively monitored mother-infant pair, laronidase during pregnancy and breastfeeding was uneventful.

Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro.

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4h to 20µM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15µM and 9 fold at 20µM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20µM) decreased the mitochondrial membrane potential by 47-64.5% at 4, 8 and 24h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20µM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12h and a 12-fold increased protein concentration at 24h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions necessary for placental development and successful pregnancy, further investigation is warranted of the impact of ROS and BDE-47 on trophoblast cytokine responses.

Antipsychotic drugs and safety concerns for breast-feeding infants.

Antipsychotic drugs prescribed to treat psychiatric symptoms during the postpartum period are secreted into breast milk. Because breast-feeding is crucial to infant development, it is important to select a medication that poses the fewest adverse consequences. Aripiprazole, haloperidol, perphenazine, and trifluoperazine demonstrate no known developmental dangers. Olanzapine, quetiapine, and risperidone are cited as safe, although monitoring is recommended. Chlorpromazine and clozapine may induce developmental concerns. There are limited safety data for asenapine, fluphenazine, iloperidone, loxapine, lurasidone, paliperidone, pimozide, thioridazine, thiothixene, and ziprasidone. Clinicians should choose medications considered to be the safest and prescribe them at the lowest effective doses.

Using nitrofurantoin while breastfeeding a newborn.

QUESTION: My patient has a urinary tract infection and is currently breastfeeding. Her son is only 3 weeks old. Is nitrofurantoin a safe antibiotic for treatment? ANSWER: The use of nitrofurantoin in breastfeeding mothers is generally safe, as only small amounts transfer into the breast milk. Despite the lack of documented reports, there is a risk of hemolytic anemia in all newborns exposed to nitrofurantoin owing to their glutathione instability, especially in infants with glucose-6-phosphate dehydrogenase deficiency. Although some suggest that nitrofurantoin be avoided in infants younger than 1 month, studies have noted that glutathione stability might be established by the eighth day of life. In infants younger than 1 month, an alternative antibiotic might be preferred; however, if an alternative were not available, the use of nitrofurantoin would not be a reason to avoid breastfeeding. In any such case the suckling infant should be monitored by his or her physician.