Anticonvulsant use during lactation.

The issue of prescribing anticonvulsant drugs during lactation is clinically important, but also complex. Data for some drugs are completely lacking and for other drugs information is only available from single dose or short term studies or case reports. Moreover, limited knowledge exists about the practical impact of the drug concentrations found in breast milk and there are great methodological problems in the assessment of possible adverse drug reactions in infants. Nevertheless, based on current knowledge, some recommendations can be suggested. Treatment with carbamazepine, valproic acid (sodium valproate) and phenytoin is considered compatible with breastfeeding. Treatment with ethosuximide or phenobarbital (phenobarbitone)/primidone should most probably be regarded as potentially unsafe and close clinical monitoring of the infant is recommended if it is decided to continue breastfeeding. Occasional or short term treatment with benzodiazepines could be considered as compatible with breastfeeding, although maternal diazepam treatment has caused sedation in suckling infants after short term use. During long term use of benzodiazepines, infants should be observed for signs of sedation and poor suckling. Only very limited clinical data are available for the new generation anticonvulsant drugs and no clearcut recommendations can be made until further data are present. If it is decided to continue breast feeding during treatment with these drugs, the infant should be monitored for possible adverse effects. In general, the drug should be given in the lowest effective dose, guided by maternal serum or plasma drug concentration monitoring. If breast feeding is avoided at times of peak drug levels in milk, the exposure of the infant can be reduced to some extent. As breast milk has considerable advantages over formula milk, the benefits of continuing breast feeding should always be taken into consideration in the risk-benefit analysis.     

Antibiotics and breast-feeding: a critical review of the literature

Continuous breast-feeding, an integral component of the postpartum period, is often threatened upon maternal initiation of antibiotics. The real risk of antibiotic use while breast-feeding must be carefully analysed with regard to all the variables that influence the extent of antibiotic distribution into breast milk, including breast milk composition, physicochemical properties of the antibiotic (molecular weight, lipid solubility, pH, protein binding), length of feeding, and maternal disposition. In addition, infant disposition, including ability to absorb, metabolize, eliminate, and tolerate any amounts of antibiotic, must also be considered prior to maternal administration of antibiotic. The milk to plasma (M/P) ratio is a frequently quoted parameter used to predict drug distribution into breast milk. However, its utility is questionable and often fraught with misinterpretation. An alternative approach when the amount of antibiotic concentration in breast milk is known (through clinical trials) is to calculate an estimated or expected infant drug exposure factoring in known/expected milk consumption, drug concentration and bioavailability. In this review, the following antibiotic classes and current literature regarding their distribution into breast milk are critically reviewed: beta-lactam antibiotics, fluoroquinolones, sulfonamides, macrolides, aminoglycosides, tetracyclines, nitrofurantoin, metronidazole, vancomycin, clindamycin and chloramphenicol. In the majority of instances, these antibiotics do not distribute into breast milk in sufficient concentrations to be of any clinical consequence in the breast-feeding infant.     

剖宫产围手术期预防性应用抗生素的探讨

目的:探讨剖宫产围手术期抗生素预防感染的合理应用。方法:对100例剖宫产手术随机分为围手术期用药组(试验组)和术后用药组(对照组)各50例。观察术后体温、术后感染、母乳喂养情况、药物不良反应及用药费用等。结果:术后感染率两组比较差异无统计学意义,试验组术后体温正常、药物无不良反应、抗生素应用少及早期母乳喂养率高,两组差异有统计学意义。结论:剖宫产围手术期预防性应用抗生素安全、有效且剂量小、疗程短、花费低,优于术后常规用药。     

Accumulation of atenolol and metoprolol in human breast milk

Summary Passage of the cardioselective beta adrenoceptor antagonists atenolol and metoprolol from serum to breast milk was assessed in 7 lactating women treated with atenolol due to hypertension developing during pregnancy, and in 3 healthy women who agreed to take metoprolol at cessation of lactation. For both drugs, the concentration in breast milk was higher than that in serum at every time studied, and the resulting AUC values were 1.5–6.8 times (atenolol) and 2.6–3.7 times (metoprolol) greater in milk than in serum. Assuming ingestion of 75 ml milk per meal, and as the maximum milk concentrations recorded were 6.35 µmol/l (atenolol) and 2.58 µmol/l (metoprolol), the data indicate that the dose following a meal at the time of maximum maternal drug concentration would not exceed 0.13 mg atenolol and 0.05 mg metoprolol, and would be considerably less after the other meals. In the only infant from whom serum samples could be obtained, the plasma atenolol concentration ranged between 0 and 0.26 µmol/l. None of the atenolol-exposed infants had any sign of an effect of the beta blocker. It would seem likely that, unless renal (atenolol) or hepatic (metoprolol) function in the infant were pronouncedly impaired, breast feeding need not be interrupted due to maternal medication with ordinary doses of either of these drugs. However, the infants should be observed for signs of beta blockade.     

Metformin before and during pregnancy and lactation in polycystic ovary syndrome

Metformin improves the endocrinopathy of polycystic ovary syndrome (PCOS), facilitates conception, appears to reduce first trimester miscarriage and gestational diabetes and does not appear to be teratogenic. The concentrations of metformin in breast milk are generally low and the mean infant exposure to metformin has been reported in the range 0.28-1.08% of the weight-normalized maternal dose, well below the level of concern for breastfeeding. No adverse effects on blood glucose of nursing infants have been reported. Metformin during lactation versus formula feeding appears to have no adverse effects on infants' growth, motor-social development and intercurrent illness during the first 6 months of life. Systematic studies have not yet been done assessing how hyperinsulinemia, polycystic ovary syndrome and metformin may affect lactation.     

乳汁中药物浓度测定的研究进展

母乳喂养对婴儿来说是一种非常健康及有营养的获取能量的方式，对母亲和婴儿都有益处。患有某些疾病的哺乳母亲在进行药物治疗时，需要考虑药物是否会进入乳汁而对婴儿产生一些不良反应或对母亲产生影响。由于许多药物的哺乳期用药安全性并不十分明确，因此在临床治疗中不推荐哺乳期妇女使用。测定乳汁中的药物浓度可以明确合理的给药时间和给药剂量，提高用药安全性，对临床用药具有非常重要的意义。但乳汁成分复杂，含有大量脂质和蛋白质等干扰物质，使乳药浓度测定有一定困难。本文综述了国内外乳药浓度测定方法，以期为哺乳期合理用药提供参考。     

Excretion of paracetamol in human breast milk

Summary Breast milk and plasma levels of paracetamol were monitored in 3 lactating women after ingestion of a single 500 mg dose of paracetamol. The paracetamol concentrations were consistently lower in milk, with a mean milk/plasma AUC ratio of 0.76. This value was in close agreement with the milk/plasma partition ratio of 0.81 foundin vitro, and could be related to quantitative binding differences between the two fluids. The half-lives of paracetamol in plasma and breast milk were almost identical, with an overall mean of 2.7 h. As less than 0.1% of the maternal dose would be present in 100 ml milk, breast feeding need not be discontinued due to paracetamol treatment in conventional dosage.     

护理干预对母婴分离产妇乳汁分泌的影响

目的 探讨护理干预对母婴分离产妇乳汁分泌的影响.方法 选取母婴分离产妇160例,将其按照随机数字表法分为研究组和对照组各80例,对照组采用常规护理,研究组采用乳房护理干预,比较两组产妇产后开始泌乳时间、泌乳量及乳房肿胀发生率.结果 研究组产妇产后开始泌乳时间早于对照组,第1、2、3、4天的泌乳量均多于对照组,差异有统计学意义（P＜0.05）.产后4d内研究组乳房肿胀发生率为13.75％,低于对照组的35.00％,差异有统计学意义（x^2=6.132,P＜0.05）.两组均随访1个月,研究组母乳喂养率为85.00％,高于对照组的66.25％,差异有统计学意义（x^2=4.120,P＜0.05）.结论 乳房护理干预可加快母婴分离产妇的泌乳时间,增加乳汁分泌量,减轻乳房肿胀,保证母乳的顺利喂养.     

Anticonvulsants and breast feeding: a critical review

Progress in the diagnosis and management of seizure disorders and the availability of effective anticonvulsive medications has enabled increasing numbers of epileptic women of child-bearing age to raise families. Breast feeding, which these women may wish to choose, provides health, nutritional, immunological, developmental, social, economic and environmental benefits. The traditional anticonvulsants, such as phenytoin, carbamazepine and valproic acid (valproate sodium), are generally considered safe for use during breast feeding; however, observation for adverse effects is recommended. The use of phenobarbital while breast feeding is controversial because of its slow elimination by the nursing infant. The newer anticonvulsants, such as clobazam, felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin, are used mainly as adjunctive therapy. Data on the use of these drugs in pregnancy and lactation, and regarding long term effects on cognition and behaviour, are sparse. Weighing the benefits of breast feeding against the potential risk to the nursing infant, breast feeding is considered to be safe when the mother is taking carbamazepine, valproic acid or phenytoin. Infant monitoring for potential adverse effects is advisable when the mother is taking phenobarbital, clobazam, gabapentin, lamotrigine, oxcarbazepine or vigabatrin. Monitoring of infant serum drug concentrations is advisable but not compulsory. The use of felbamate, tiagabine and topiramate during breast feeding should await further study.     

Drug excretion into breast milk--overview

Breastfeeding is the optimal form of infant feeding for the first months of an infant's life, and the majority of healthy women initiate breastfeeding after the birth of their infant. However, women on medication may default to formula feeding or not taking their drug therapy for fear of exposing their infant to the medication through the breast milk. Although the majority of medications are considered to be compatible with breastfeeding, cases of significant infant toxicity exist, suggesting a case by case risk assessment to be made before the mother initiates breastfeeding or drug therapy. Unfortunately, current clinical risk assessment is often compromised by the paucity of data, as studies in breastfeeding women and their infants are ethically difficult to conduct. Circumventing the ethical constraints, approaches have been proposed to estimate drug excretion into milk from physicochemical characteristics of the drug, which diffuses through the mammary gland epithelia. However, as our understanding on drug transfer mechanisms increases, it has become abundantly clear that carrier-mediated processes are involved with excretion of a number of drugs into milk. This article provides an overview of the benefits of breastfeeding, the effect of medication use during breastfeeding on maternal decisions and infant health, and factors determining infant exposure to medication through the breast milk.     

The safety of amoxicillin/clavulanic acid and cefuroxime during lactation

Breast-feeding is considered the gold standard for infant nutrition. In spite of statements about the safe use of drugs in lactation by the American Academy of Pediatrics, medical professionals remain confused regarding the management of drug therapy in nursing mothers, and this can lead to suboptimal prescribing and poor compliance. The aim of our study was to evaluate the safety of 2 of the newer antibiotics, amoxicillin/clavulanic acid and cefuroxime, during lactation. Breast-feeding women who called a drug consultation center to obtain information about the potential risks of amoxicillin/clavulanic acid (67 women) and cefuroxime (38 women) were prospectively recruited. As a control group, women who were treated with antibiotics known to be safe during lactation were recruited: amoxicillin (n = 40) for the amoxicillin/clavulanic acid group and cephalexin (n = 11) for the cefuroxime group. Women in the control group were matched for indication for antibiotic therapy, duration of treatment, and maternal age. Participants were interviewed after treatment termination regarding adverse reactions during therapy. In the amoxicillin/clavulanic acid group, 15 infants (22.3%) had adverse effects, and the rate increased with dosage (P = 0.0139). This was significantly higher than the amoxicillin group, where 3 infants (7.5%) had adverse effects (P = 0.046, relative risk (RR) = 2.99, 95% confidence interval (CI) 0.92-9.68). However, there were no significant differences between rates of specific events. The rate of adverse effects in the cefuroxime group (2.6%) was not significantly different from that in controls (9%) (P = 0.58, OR = 0.92, 95% CI 0.94-1.06). All adverse effects were minor, self-limiting, and did not necessitate interruption of breast-feeding. Our data suggest that amoxicillin/clavulanic acid and cefuroxime may be safe during lactation. Larger studies are needed to confirm these findings.     

Olanzapine treatment during breast feeding: a case report

Postpartum psychosis constitutes a severe complication that entails risk for both mother and child. Little is known about the use of olanzapine in the treatment of postpartum psychosis. In previous studies, it has been reported on mothers receiving relatively low doses of olanzapine. We report a 38-year-old patient who was admitted to the hospital for an acute psychotic exacerbation. She was breast feeding her 5-month-old child, and she wished to continue breast feeding. Olanzapine treatment was started with a daily dosage of 15 mg. The weight-corrected maternal dose was 270 mug/kg. The olanzapine concentration in the mother's plasma was 24 ng/mL. The analysis of olanzapine in breast milk applying two different high-performance liquid chromatography procedures revealed similar results: 12.2 ng/g without and 11.5 ng/g with additional hydrochloric acid extraction, respectively. In addition, breast milk of an unmedicated mother was used for establishing the analytical procedure so that the validity of the results was better confirmed. The milk-plasma ratio arising from our data was 0.5, and the relative infant dose was 0.3%. The olanzapine concentration was below the limit of detection (<5 ng/mL) in the infant's plasma sample. No adverse effects were noticed, and the mother experienced a rapid improvement in her psychopathology during her hospital stay. In future studies, long-term follow-up of both mother and child would be useful.     

全方位护理对剖宫产产妇母乳喂养的影响

目的：探讨提高剖宫产产妇的乳汁分泌和母乳喂养率的护理措施。方法：本文对剖宫产术后母婴进行了全方位护理,指导产妇早进食、早活动、合理膳食,宣传母乳喂养,坚持做好早接触、早吸吮,多做耐心细致的解释和具体方法的指导,促进和保持乳汁的分泌,为产妇提供良好的休养环境。结果：观察组产妇的泌乳始动时间明显早于对照组,48h泌乳量明显较对照组充足,术后开始下床活动时间明显早于对照组（P〈0.05）。结论：全方位护理可提高剖宫产产妇的乳汁分泌和母乳喂养率。     

Keeping abreast of the times: the Tauranga Infant Feeding Survey.

An infant feeding survey revealed that 77% of 187 mothers, whose babies were born over a three month period in the Tauranga maternity annexe, were breast feeding on discharge. Fifty-seven percent of the total breast fed for at least three months. The feeding pattern did not vary with ethnic group nor with previous breast feeding experience. Short-term breast feeders were younger and had fewer children than either the bottle feeders or long-term breast feeders. Bottle feeding tended to occur with extremes of maternal age. Breast feeders sought more advice during pregnancy and confinement. Overall, the most common reason for changing to bottle feeding was "insufficient lactation", although this reason rarely stood alone. Many mothers experienced difficulties with artifical feeds and made at least one milk change, nearly half receiving no advice. Solid food was most commonly introduced at three months.     

Minimising the adverse effects of ketorolac.

Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.     

Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child

Objective: To investigate the transfer of lamotrigine in pregnancy and during lactation from a mother on lamotrigine treatment to her child. Methods: Concentrations of lamotrigine were measured by high-pressure liquid chromatography in umbilical cord serum and in serum samples of the mother and her child as well as in the mother's milk during the first five postpartum months. Results: In the child lamotrigine serum concentrations (up to 2.8 μg ml⁻¹) comparable to those usually achieved in active treatment with lamotrigine were found not only after birth, but also during lactation. A considerable amount of lamotrigine (2–5 mg per day) was excreted in breast milk. No adverse effects were seen in the child. Conclusion: The transfer of lamotrigine taking place during pregnancy and lactation should not be neglected. In this case the child should be thoroughly observed for potential adverse effects. Received: 27 June 1996 / Accepted: 7 October 1996     

Use of psychotropic medications in treating mood disorders during lactation : practical recommendations

Many new mothers who need antidepressant or mood-stabilising drug treatment may wish to breastfeed their infants, but are hesitant to do so because of possible harmful effects of the medication on the infant. This article reviews current data on drug excretion into breast milk and the effects on the breast-fed child, and provides recommendations for the use of the different psychotropic drugs in lactating women.Relevant literature was identified through systematic searches of MEDLINE, EMBASE and the Science Citation Index Expanded (ISI) from 1966 to February 2005. The present knowledge is based on the accumulation of case studies. No randomised controlled trials in breast-fed infants have been performed and there is a lack of long-term follow-up studies.Use of SSRIs and TCAs (except doxepin) is compatible with breastfeeding. However, if treatment with an SSRI is started in the postpartum period, fluoxetine and citalopram may not be drugs of first choice. With regard to other antidepressants, such as venlafaxine, trazodone, mirtazapine, reboxetine, moclobemide and other MAOIs, very little knowledge exists. Breastfeeding should be avoided while using lithium. Carbamazepine and sodium valproate (valproic acid) are generally better tolerated by the breast-fed infant than lithium. Data on lamotrigine are still sparse. Knowledge is also scarce on the novel antipsychotics and thus recommendations in lactating women cannot be made for these agents. It is unwise to expose infants unnecessarily to drugs that may have severe adverse effects. As such, clozapine should probably be avoided because of the risk of agranulocytosis.Our knowledge of the impact of drug exposure through breast milk is still limited. Infant drug exposure is, however, generally higher during pregnancy through placental passage than through breast milk. Despite the low dosage transferred to the infant through breast milk, premature infants and infants with neonatal diseases or inherited disturbances in metabolism may be vulnerable to such exposure.     

低频电刺激结合按摩点穴对剖宫产产妇泌乳的影响

目的 观察低频电刺激结合乳房按摩点穴对剖宫产产妇乳汁分泌的影响.方法 将1 200例剖宫产产妇随机分为对照组600例和实验组600例.对照组给予常规的母乳喂养支持、宣教及床边指导.实验组产妇在对照组同样的护理基础上,于术后12 h开始进行低频电刺激结合乳房按摩点穴治疗.结果 实验组泌乳始动时间明显短于对照组,泌乳量较对照组多,出现乳房胀痛的程度明显低于对照组,差异有统计学意义(P＜ 0.05).结论 低频电刺激结合乳房按摩点穴治疗能促进剖宫产产妇乳汁分泌、泌乳始动时间提前、泌乳量提升,减少乳房胀痛的发生,为母乳喂养提供了保障,此方法可操作性强,值得推广.     

Antibiotics and lactation: An overview of relative infant doses and a systematic assessment of clinical studies

Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling. The infant exposure has been calculated and expressed as a percentage of a normal infant therapeutic dose. Sixty‐six studies were included in five antibiotic groups (broad‐spectrum penicillin, cephalosporins, macrolides and lincosamides, quinolones and sulphonamides). Cephalosporins were the most studied group of antibiotics (n = 21). Fifteen studies met all the criteria of “mother exposure to antibiotic”. Six studies met every criterion related to “plasma sampling”. Only one case report met all listed criteria for lactation studies. The correct calculation of infant exposure to antibiotics via the milk:plasma ratio (AUC) varies between 13% for macrolides and 38% for broad‐spectrum penicillin. The highest assessed exposure as a percentage of infant therapeutic dose was for metronidazole (11%). The studies meet to a limited extent with the quality standards for lactation research. The breastfed infants are exposed to a subtherapeutic concentration of antibiotics.