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Unnatural constituents of breast milk—medication, lifestyle, pollutants, viruses
Unnatural constituents of breast milk-medication, lifestyle, pollutants, viruses Jean Golding Unit qf Paediutric and Perinatal Epidemiology. Institute of Child Herrlth. ~Jniverrity of Bri.
Abstract It is welt recognised that although nutritionally breast milk is the optimal food for babies, there are a number of caveats to this, based on the consequences of the modern lifestyle. Here we have considered ways in which the young breast fed child may be exposed to various environmental and medical contaminants which might cause adverse reactions and to which he/she may not otherwise be exposed. These substances are divided into four different areas: (i) medication taken by the mother; (ii) exposure to possibly addictive drugs taken by the mother: (iii) exposure to pollutants mainly from the maternal diet or as the result of her occupation; (iv) viruses. The infant who consumes breast milk may be exposed to a variety ofchemicals which may have untoward effects on his/her immediate health and temperament and future development. Potentially hazardous substances ingested by the breast fed infant include medicaments (or their metabolites) that may have been ingested by the mother. potentially addictive common neurotoxicants such as nicotine, caffeine and alcohol, illicit drugs such as biphenyls and diheroin and cocaine, and pollutants such as polychlorinated chlorodiphenyltrichloroethane (DDT). There is a paucity of good information on which to base reliable estimates of the harm that this may cause the child. Although breast feeding is known to protect against bacterial infection, a number of viruses are excreted in the breast milk which may infect the child asymptomatically (e.g. cytomegalovirus, Epstein-Barr virus) and which are not known to be harmful, as well as human immunodeficiency virus (HIV) excretion which, in contrast, does appear to increase the risk of the child becoming infected. Balancing the risk of infection to the child born to an HIV infected mother, results in tie proposition that known HIV positive women in developing countries (where the risk of gastrointestinal infection is high) should continue to breast feed but those in the developed world (where the risk of gastrointestinal infection is lower) are better advised to bottle feed. 0 1997 Elsevier Science Ireland Ltd. Keywords:
Breast feeding: Medication; Addictive drugs; Pollutants: Viruses
0378-3782/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reservctl PII SO3?X-3782(97)00052-2
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1. Medication A study in Canada of 838 children who were being breast fed by mothers who were on medication of various sorts reported that 11.2% had minor adversereactions [I]. This proportion must be considered the tip of an iceberg since these were recognised adverse reactions with immediate demonstration. Identification of any long-term adverse outcome, not obviously related, could be more important but will certainly be more difficult to demonstrate. Of the minor adverse reactions identified, the three most common ones were: diarrhoea in the child due to antibiotics being taken by the mother; drowsiness associatedwith the mother’s intake of analgesics or narcotics and irritability associatedwith the mother’s exposure to antihistamine. Most drugs can be transmitted through breast milk to the infant [2]. Drugs administered to a lactating mother are passedby way of the epithelial cells of the mammary glands to the milk. The rate of diffusion of therapeutic agents across the mammary glands may be modulated by the physio-chemical properties of drug molecules. Thus, lipid-soluble drugs with low molecular weight pass through the membranein large amounts. Acidic drugs, such as barbiturates and benzyl penicillin, reach the milk less readily than alkaline drugs, such as erythromycin, antihistamines or alkaloids. The concentration of the drug in the milk depends on the dose administered, the duration of treatment, the daily quantity of milk secreted, the mother’s health, the mother’s drug tolerance and her genotype. Examples of drugs that may be harmful to the nursing infant have been listed below [2] with the adverse consequences in brackets: chloramphenicol (inhibition of bone growth), sulphonamides (jaundice), salicylates (disturbance of blood coagulation), paracetamol (methaemoglobinaemia), barbiturates (drowsiness, weak suck reflex), phenytoin (drowsiness, weakness),antidepressants(tremor, insomnia), anticoagulants (haemorrhage), steroid hormones (jaundice, disturbed bone growth) and thyroid hormones (hyperthyroidism). Given the freely available information about the numbers of drugs that reach the young infant via the breast milk it may seemsurprising that in the maternity hospital drugs are freely administered to women who have just delivered but intend to breast feed. In Norway [3] a study of 970 women delivered vaginally in five hospitals showed that 90% had received drugs; this excluded from consideration laxatives, oxytocics, vitamins and iron as well as long-term medication. The drugs that were given to the mothers included hypnotics (86% of mothers) and analgesics(65-95%). The author comments that the frequent use of hypnotics indicates that breast feeding mothers were treated like ordinary hospital patients rather than mothers about to breast feed a young infant. She noted that for most of the drugs used routinely on the post-natal wards there was little or no data on excretion in breast milk upon which to base any judgement about the appropriatenessof prescription. The commonly used drugs are the most worrying in regard to effects on the child, since if there are adverse consequences,large numbers of children may be affected.
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Aspirin is freely taken by large numbers of women, and yet has been banned from administration to young children because of substantial evidence linking it with Reye’s Syndrome. Nevertheless,mothers expose their child to aspirin in breast milk without realising that this may be equivalent to giving aspirin to their baby. Although it is generally thought unlikely [4] that a single dose of aspirin will result in a high dose to the young breast fed child, salicylate will be present in the milk of mothers who are on long-term high dose salicylate therapy. One child, for example, was shown to have very high plasma levels while being breast fed by a mother who was receiving 2.4 g of aspirin per day. In this situation there is a significant risk of both kernicterus and intracranial haemorrhage [51. Phenylbarbitone is a barbiturate used formerly as a sedativebut currently mainly as an anticonvulsant. One study of 42 breast fed infants of epileptic mothers who were on this medication, was reported to show poor weight gain and a high incidence of vomiting and inadequate suckling [6]. Although this report was written with authority, on returning to the actual paper cited, the 42 infants were not, in fact, all exposed to breast milk let alone to phenylbarbitone. Only thirteen of the children were breast fed and phenytoin, primidone and carbamazepinewere taken by some of the mothers rather than phenylbarbitone. It is therefore very difficult to identify the adverse effects of a particular drug. The authors did show, however, that the breast fed group lost weight in the first five days when compared with the bottle fed or control groups of children [7]. A casereport of one child who died while being breast fed by an epileptic mother taking phenylbarbitone showed a very high level of phenylbarbitone in the infant’s blood. It was concluded [6] therefore that it is unsafe for a mother to continue to take this drug while breast feeding. However, a review of the literature published in 1987 [S] stated that “most mothers taking anticonvulsant drugs may safely breast feed their children”. This was despite the author noting that significant amounts of the drugs do pass into the milk. The ratio of the drug content of breast milk to the serum level of the mother was given as 19% for phenytoin, 41% for carbamazepine,36% for phenylbarbitone and 70% for primidone. The samestudy of 42 children 17) quoted before is used to reach a substantially different conclusion. It is therefore obvious that not enough is known about anticonvulsants and their effecr via breast milk on susceptible children. Other substancesthought to have an effect on the developing infant are antidepressants and tranquilisers. Benzodiazepinesmay cause problems since the metabolising ability of the young baby may be impaired and the drugs accumulate in the susceptible infant [9]. One study of the antidepressantlithium [lo] showed that the breast fed child of a mother consuming this drug had detectablelevels in the serum, especially in the first two weeks of life. The authors suggestedthat “Arguments can be presented both for and against the view that a lithium treated woman should be permitted to breastfeed her child. On the one hand during the pregnancy the child has been exposedto the samelithium concentration as the mother for many months and it seemsunlikely that exposure to a lower lithium concentration for a few more months will do any harm. On the other hand any unnecessary ingestion of drugs is undesirable and potentially dangerous”.
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2. Exposure to possibly addictive drugs 2.1. Caffeine
Caffeine is consumed by many women. Currently there is no advice to breast feeding mothers about the possible effects of high caffeine consumption on the breast fed infant. The studies concerning the ingestion of caffeine during breast feeding are very limited. One [ 1l] studied five breast feeding mothers and observedthe results of a standardisedoral dose of caffeine. It was shown that caffeine does not diffuse freely and that the concentrations in breast milk are lower than in maternal serum. The authors suggestedthat the breast fed infant would receive only a low dose of caffeine after the mother had drunk a single cup of coffee but with repeated maternal ingestion, the caffeine would accumulate, depending on the rate of elimination in young infants. A further study [12] of fifteen mothers who were given a single dose of caffeine showed that in eleven of these the caffeine was excreted in the breast milk but no caffeine was found in any of the children’s urine samples.However, there was substantial data suggesting that caffeine metabolism differed in each of the women resulting in different levels in the breast milk. It is possible that children are not exposed to significant dosesof caffeine from the breast milk if the mother consumes relatively small amounts-but caffeine in the breast milk of a high consumer may be more significant. 2.2. Alcohol
Nursing mothers are frequently advised to take alcohol containing drinks on the understanding that this helps in the breast feeding process by relaxing them and aiding the ‘let down reflex’ [ 131. Although experienced breast feeders are often convinced that this enablesthe child to be more readily fed, there is no real evidence of this. It is now well-established [14] that the alcohol drunk by a nursing mother affects the odour of the milk and the feeding behaviour of the infant. Although the young child sucks more frequently during the first minute of breast feeding after the mother has had an alcohol containing drink, he/she consumessignificantly less breast milk during such a feed [ 141.The ethanol is excreted in the breast milk and is there in a similar concentration to that found in the peripheral blood of the mother [ 15,161. Nevertheless,the amount of alcohol that a breast fed child could receive is thought to be relatively low and unlikely to causeharmful effects if the maternal use of alcohol is temperate [ 161. The key question concerns whether the alcohol intake in breast milk can have an adverse effect on the developing child. One study has shown that mice exposed to alcohol in breast milk are substantially less active comparedwith unexposed,control new-born mice [17]. The one major study of alcohol exposure via breast milk on the developing human [ 181 suggestedthat alcohol ingested via breast milk had a slight but significant detrimental effect on motor development though not on mental development. This finding has not yet been tested in any other study. Until that has
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been done, it may be safer to suggestthat alcohol ingestion of anything other than a small amount should be avoided during breast feeding. 2.3. Illicit
drugs
When illicit drugs are taken they are usually continued throughout pregnancy and thereafter. Consequently it is difficult to untangle adverseeffects due to exposure via breast milk from the long-term results of exposure in utero. It is certainly true that a baby who would otherwise experience withdrawal effects during the early neonatal period, is less likely to do so if breast fed by a mother who is continuing to take the particular drug to which the child had been exposed in utero [ 191.Opiates, including morphine, heroin and methadoneare detectablein breast milk after maternal use, but the total amounts excreted are thought to be small. Methadone ingested in breast milk, however, may have contributed to the death of at least one infant [ZO]. In spite of this, the current recommendation [21] is that the risk to the suckling infant of ir mother taking methadone would appear to be low on the basis that the quantity of drugs that appearsin breast milk is small. Breast feeding is recommendedproviding the maternal dose is low and the mother is warned to seek medical advice if her child appearssedated. Cocaine has not yet been studied fully. Nevertheless there is a useful case report [22J of a two week old infant girl whose mother, having avoided cocaine in the last seven months of pregnancy, used some cocaine with the result that the child had a major outburst responsewith marked neurological problems which were transient in nature. In this case levels of cocaine were found in the maternal milk for as long as 36 hours after she had used it. It seemslikely therefore that children of breast-feeding cocaine using mothers would be adversely affected. The effects of cannabis on the breast fed child have not been studied. However, on the basis that data concerning cannabis intake during pregnancy have shown little in the way of long-term adverse effects, there is a possibility that breast feeding while using cannabis may not have major detrimental consequences,but further studies of this are awaited. 2.4. Cigurette smoking
There is now substantial evidence to show that smoking mothers who breast feed are exposing their children to cotinine and nicotine with a concentration of up to I 14 mg/l ]23]. That this is absorbedby the infant is shown by a number of studies. For example, a study in Australia [24] of 79 infants whose mothers were current smokers showed a linear relationship between the number of cigarettes smoked and the cotinine level in the infant’s urine (r = 0.79, P
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in the mother’s plasma. There was a striking difference in exposure of the infant according to whether the mother had smoked shortly before breast feeding. In Canada 33 infants whose mothers smoked were studied [26]. The correlation coefficient between the number of cigarettes smoked by the mother and the breast milk cotinine concentration was statistically significant (r = 0.69, P = 0.0002). Similarly the urinary cotinine of the babies increasedwith the cotinine levels in the mother’s milk (I = 0.56, P = 0.02). In Germany, [27] a study of 23 nursing mothers showed a linear correlation between nicotine in the serum and nicotine in the milk (r = 0.70) and again that the nicotine concentrations in milk were 2.9 times higher than the corresponding serum concentrations. Similarly there was a linear correlation between cotinine concentrations in the serum and in the milk (r = 0.89). A further study from Germany was concerned with 69 infants whose mothers smoked more than five cigarettes a day [28]. Those who were breast fed had urinary levels that were in the same range as adult smokers would have been. The major question concerning nicotine and cotinine in breast milk is whether this has a detrimental affect on the child. One of the earliest publications [29] related a casehistory of a six week old infant whose mother smokedtwenty cigarettesper day. Symptoms of restlessness, insomnia, vomiting, diarrhoea, rapid pulse etc., disappearedonce the mother stoppedbreast feeding her infant. In a study of four cases of so-called ‘nicotine intoxication’ occurring at three to four days of age [30], the babies refused to suck further, vomited after feeding, their skin appeared grey in colour, and they becameapathetic and flaccid. After the mothers stoppednursing the symptomsdisappeared.A further study published in 1976 [3 l] reported the symptoms of nicotine ingestion as being nausea,vomiting and diarrhoea. We show elsewhere that women who smoke are less likely to breast feed and also that once breastfeeding they are more likely to give up earlier than non-smokers.One study has looked at the volume of breast milk in smoking as opposedto non-smoking mothers [32]. A comparison of ten smokers with ten non-smokers showed that the non-smoking mothers had significantly greater breast milk volume (961 g per day) than smoking mothers (693 g/day, P < 0.001). Not surprisingly the growth of the infants of the non-smoking mothers was also greater, 550 g per fourteen days, compared with 340 g (P
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development of an intellectually sub-normal child. Nevertheless, it must be stressed that further studies are needed before too much weight can be given to this result.
3. Inadvertent exposures--pollutants 3.1. Heavy metals
Heavy metals are important in that they can have major detrimental effects on the developing brain of the young child. It has been established, for example, that increasing lead exposure results in a marked decrease in IQ level. There is no threshold effect, and the only truly safe level is zero [34]. There is, however, little evidence that lead appears substantially in breast milk. Breast milk contains only a small fraction of the mother’s blood levels [35), however, there is a significant positive correlation between the two. In Malaya, a study of 114 subjects found a correlation of 0.29 (Z’ < 0.01) between maternal blood levels and breast milk levels of lead [36]. Mercury too, results in neurological damage. Once taken up the methyl mercury remains in the brain for a considerable period of time, and symptoms may progress over a long period [37]. The most convincing data on the adverseeffects of mercury come from the unfortunate Minamata area of Japan. Mothers accidentally exposed during pregnancy and lactation produced high levels of fetal and infant abnormal brain development. The methyl mercury concentration in the mother’s milk was 3-6% (63 mg/l) of that in their blood [373. In less extreme casesdetectablelevels of mercury have been found in breast milk. In Spain [38], for example, the concentration was 9.5 mg/l, but it is not known if this level is harmful to the infant. The neonateof an exposedmother will be born with an increasedbody burden, mostly concentratedin its brain, and then lactation will add au extra load. As with lead, the infant’s developing nervous system is much more susceptible to mercury than the fully developed nervous system would be [39]. 3.2. Pesticides and other organochlorine
compounds
The most worrying pollutants in terms of breast feeding are the organohalidessuch as polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs) and dichlorodiphenyltrichloroethane (DDT). DDT and its metabolite DDE (dichiorodiphenyldieldrin) were used widely as pesticides in the 1950s and 1960s. The detectable levels of DDT and DDE in breast milk were noted as early as 195I. Although no longer used in the West, DDT is still used in many developing countries and therefore is found in products, such as cigarette tobacco, grown in those countries. All organohalides are resistant to physical degradation and biologic metabolism and are widespreadin the environment. Once ingested they are stored in fat tissue and unlikely to be excreted unless through breast milk. Thus lactation is the only way in which a mother is likely to get rid of substantial amounts of these
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substances.This may improve her health, but will passthe burden to the tissuesof the young infant [40]. Studies in Japanof women occupationally exposedto PCBs found that there was a positive correlation between the length of time their children had been breast fed and the PCB levels in the child’s blood [41]. In 1975, in the USA, 1038 breast milk sampleswere analysedfor PCBs. Only 1% had no contamination and 30% had levels above 0.05 ppm [42]. A later study from the USA looked at other hydrocarbon insecticide residues in human milk and found that evidence of contamination with dieldrin, heptochlorepoxide and oxychlordane was substantial and varied significantly between different areas within the USA [43]. A study from Australia in 1979/1980 showed that levels of organochlorine pesticides in breast milk were positively related to maternal age-the older the mother the higher the levels [44]. A major study in North Carolina [45] showed no relationship, however, between the mother’s age, race, occupation or cigarette smoking and PCBs, but did find that regular alcohol use was associated with somewhathigher levels of PCBs in breast milk. DDE on the other hand did increase with age and was higher in blacks and in smokers. This study found that the concentration of PCBs and DDE in breast milk declined with the continuing course of lactation with values at six months about 20% less than those at the beginning of lactation. A study from Michigan showed that fish consumption was correlated with PCB levels in maternal serum and maternal milk. It showed that these levels increased with age, but were not related to social class, parity or body weight [46]. The key question is whether these chemicals have any adverseeffects on the young child. It has been suggestedthat health risks to the offspring are greater for exposures during lactation than during pregnancy [47]. In the short-term, however, the North Carolina study [48] showed no effect on growth or morbidity. In Michigan, levels of PCBs, PBB and DDT in the young child were obtained at four years of age. The length of time the child had been breast fed was the most important determinant of its burden of these chemicals [49]. One study from the USA looked at eighteen children aged four to six who had been exposed to PBB in utero and/or through breast milk. In comparison with normative test data, those children exposed to PBBs were within the normal range in all areas assessed.Nevertheless, within the children, the amount of PBB stored in fat was shown to be inversely related to some of the developmental scores [50]. The North Carolina cohort were examined at ages two, three, four and five and, although at two years, the Bailey scalesappearedto show deficits in the children who had been most exposed, no such differences were found in later childhood [51]. As Nebert et al. stated [52] “Since man is at the end of the food chain, persistence of heavily halogenated PCBs and PBBs appears to be with us at least for the foreseeable future.... breast feeding by PCB contaminated mothers will lead to an enhancedingestion of PCBs in these infants from birth. This transfer of PCBs from one generation to the next is also occurring with PBBs. It therefore should be emphasisedthat one should be on the look out, at least for the next several decades, for numerous possible clinical effects-including subtle changesin intelligence and long-range effects causing cancer in PCB exposed and PBB exposed individuals”.
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3.3. Other pollutants Very little data concerning other pollutants is currently available. There are. however, reports of atlatoxin excretion in breast milk of mothers in Africa [53]. The authors warn that given the adverse effects of such exposure in controlled animal experiments (where immunity, liver function, nutrition and survival were affected). the possible long-term consequencesof exposure of the infant as a result of a&toxin ingestion by the mother, should be considered seriously.
4. Viruses
Although much research into the protective effect of breast milk in relation to various infective organisms has been undertaken, less concern has been expressed over possible viral transmission through breast milk. Studies have shown, however, that cytomegalovirus (CMV) infection is transmitted through breast milk. One London group followed 253 infants from birth for twelve months, with urine samples being collected at birth, six weeks, three months, eight months and one year. Of the women, 123 were sero-positive and 33% of their children acquired CMV after the first week of life. The risk of the sero-positive mothers passing the infection to their child was greatly increased if they were breast fed. Among the 64 infants who were breastfed for longer than twelve weeks, 42% becameinfected; of those breastfed for less than twelve weeks, 30% became infected, whereas only 19% of those who did not breast feed at all became infected [54]. CMV infection acquired in this way is seldom symptomatic, although it has been associatedwith pneumonitis. Similar results were found in the USA [55], where a study of the breast milk of 41 sero-positive women showed that 69% of those for whom CMV was identified in the breast milk had infants who became infected compared with 10% of those whose milk did not appearto have the virus present. Mothers who breast fed their infant fat one month or longer were more likely to pass the infection to their child than those who stopped breast feeding within one month [56]. Another herpes virus, the Epstein-Barr virus (EBV) is also shed in breast milk. A study in British Colombia took breast milk samples from 100 randomly selected women and assayedfor virus particles. Forty-six percent had EBV cells in the breast milk [57]. It was found that the EBV was more likely to be shed in breast milk as lactation proceeded,and that excretion was intermittent. The authors suggestedthat a substantial proportion of infants would be infected with EBV by this route. Certainly. it is well-known that a high proportion of children are infected with EBV in their first two years of life, and breast milk seemsa likely route. A further virus that has been reported present in breast milk is the adult T-cell leukaemia virus (ATLV), which has been reported from Japan. There, when breast milk samples were infected with ATLV, 81% of the infants who were breast fed became infected in the post-natal period [58]. Studies from Taiwan have implicated potential transmission of the hepatitis B virus (HBV). They showed the presence of HBV-DNA in colostrum from 50 carrier
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mothers and suggestedthat all babies born to such mothers should be vaccinated against HBV at birth [59]. The major discussion point concerning viral transmission, however, concerns human immunodeficiency virus (HIV). The HIV virus has certainly been detectedin breast milk [60]. Evidence that children of breast feeding mothers becomeinfected by HIV becauseof exposure via breast milk comesfrom two separategroups of studies. The first comprises a small number of instances where the mother appearsto have become infected after delivery and the presumed source of infection in the child has been the breast milk. This included ten women in Australia who received infected blood products after delivery-two of the ten breast fed children became infected [61]. In Rwanda, sixteen infants were born to mothers who sero-converted after delivery-nine of these became infected, but it was thought that five of the infants were probably infected during pregnancy or delivery. Considering only the women who sero-convertedat least four months after delivery, four of the ten infants became infected [62]. A third study in Zambia identified nineteen women who sero-converted in the year following delivery-three of the breast fed children becameinfected [63]. The other set of studies considers women who were infected during pregnancy and the incidence of infection in their children comparing those who were breast fed and those who were bottle fed. A meta-analysisof six prospective studies [64] showed an excessrisk of transmission in the breast fed group of about 14% (95% CI, 7-22%). Subsequently a large Italian study improved interpretation of the findings by controlling for potential confounding factors including gestation, birthweight, mode of delivery and maternal drug addiction [65]; the adjusted odds-ratio for breast feeding (versus formula feeding) was 2.55 [95% CI, 1.03-6.371. A study from Kenya [66] followed 365 children whose mothers were infected with HIV-l and showed that two factors only were predictive of sero-conversion-marriage and prolonged breast feeding-of fifteen months or more. There was no comparisonwith a never breast fed group-presumably becauseall babies were breast fed. Much discussion, therefore, has taken place with regard to the pros and cons of an HIV infected mother breast feeding her child. Whereasin the developedworld where artificial feeding appearsto have little effect on infant mortality, the choice seems clear-a mother who is clearly infected should be advised not to breastfeed the child, in the developing world, the balance of risks are by no means clear. Statistical techniques have been used to try to devise appropriate decision trees indicating the circumstances in which an infected mother should be advised to breast rather than bottle feed. The models, however, rely on a valid estimate of the relative risk of infant death associatedwith bottle feeding. As we have shown, this is not a statistic that is easily come by. A study by Hu et al. [67] suggestedthat, if the under five mortality rate for breast fed infants is 25%, and the relative risk associatedwith bottle feeding is 3, the post-natal transmission rate associatedwith breast feeding should be at least 67% before bottle feeding should be advised. Again, if the excessmortality is 10% and the increased risk associatedwith bottle feeding is 2%, then bottle feeding should be advised if the post-natal infection risk from breast feeding is in excess of 10%. As pointed out in correspondence,however [68], the situation is far more complex, since in developing countries the women rarely knows her HIV status.
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Cutting [69] points out the other major problem in recommending artificial feediag--the cost. This can be as much as nine times the daily wage of a hospital cleaner in Uganda. Clearly discussion of priorities is needed in this situation and this should take place at high level. 5. Discussion “Man is exposed to innumerable chemicals from sources in the natural environ-. ment and the work place. Some of these chemicals especially the lipophiiic and persistent organohalogenssuch as DDT, PCB and the dioxins accumulate in human fat tissues and are excreted mainly by breast milk. Human milk in general contains 10-50 more of these contaminants than do cows’ milk or milk substitutes: even though the period of breast feeding is short in comparison to a life time, these chemicals persist in the body and enter it at a sensitive phase of its development. There should be a constant awarenessof this source of potential toxic substancesfor the breast fed infant.” [70]. The question of how mothers should cope with this threat is unresolved. There is some evidence that eliminating animal products from the diet may be useful in reducing the level of contaminants in the breast milk. A study of twelve vegetarian women who consumed no animal products for religious reasonsfound the levels of sixteen of seventeenmeasuredcontaminantsin their breastmilk to be lower than that in the milk of typical American women. The one group of pollutants which were at similar levels to the rest of the country, however, were the PCBs 2711.In a review published in 1981, Barr [72] stated that “Human breast milk is decidedly the preferred food for human infants and breast feeding is the preferred method of feeding. On the other hand it should be recognised that formula feeding by bottle is widely accepted as an alternative with apparent safety and good results in the majority of cases. There are circumstances in which formula feeding may be necessary or even desirable. The question is does contamination of breast milk constitute a reason to discourage breast feeding?” This begs the question whether breast feeding with contaminated milk produces adverse consequencesin the infant. He goes on to say “In the current situation we can opt for one of two extremes or choose some spot in the middle ground. It has been advised that mothers with burdens of polyhydrogenated biphenyls or other environmental contaminants do not breast feed at all. This certainly would avoid adding to the body burden of the infant who had already been transplacentally exposed. However, such advice, if taken. would mean that few mothers would breast feed their infants since virtually all mothers have contaminants in their milk, mainly at levels above those permitted by law in other food stuffs”. Although he wrote in 1981, the question as to whether heavily contaminated mothers should be identified and advised not to breast feed i> still under debate. Far more important probably, are the exposures of the infant to those potentially addictive drugs, nicotine and cotinine, ethanol and the illicit drugs particularly cocaine, heroin and other opiates. A question must also be raised about the common
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medications taken by mothers. Is consideration ever given to whether tests have been done on breast milk to assessthe amount of a drug or its metabolites that reach the young child, and what effect they might have? Mothers should be made far more aware of the potential problem of consuming any of these substanceswhile breast feeding. A smoking mother currently believes she is protecting her child if she goes outside to smoke, but does not realise that the smoke inhalation by the child is not the only adverseeffect that might occur if she is breast feeding. A mother who is taking medication of various sorts rarely considers whether this may affect her breast fed infant and yet most drugs are excreted into the breast milk with consequenceslargely uncharted [9]. In general there are a number of different preparations available for a given maternal condition, and thus information on the optimum medication for the breast fed baby should be available. Much of the current advice on breast feeding and medication is based on information concerning the levels of drug in the breast milk as opposed to the maternal serum, and the relationship of the dose to the baby in relation to the therapeutic dose. This begs the question of the possible adverse reactions of a baby in receipt of low levels of a medication for which there are no immediate indications. In these circumstancesit is unlikely that the baby will reap any benefits.We would concur that “further research is urgently neededto determine maternal medications safe for nursing infants” [71]. References [l] Ito S, Blajchman A, StephensonM et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am .I Obstet Gynecol 1993;168:1393-9. 121Basu TK. Nutritional factors and dispositions of pharmacological chemicals in prenatal and neonatal life. In: Kacew S, Lock S, editors. Toxicologic and pharmacologic principles in pediatrics. New York: Hemishere, 1988:17-40. [3] MathesonI. Drugs to mother and infant in the maternity ward. A survey at five university hospitals in Norway. Saertrykk av Tidsskrift for Den Norske Laegeforening Nr22 1989;109:2118-22. [4] Brooks PM, Needs CJ. NSAIDS in lactating women. In: Famaey JP,Paulus HE, editors. Therapeutic applications of NSAIDS: subpopulations and new formulations. New York Marcel Dekker, 1992:157-62. [5] Rumack CM, Guggenheim MA, Rumack BH et al. Neonatal intracranial haemorrhageand maternal use of aspirin. Obstet Gynecol 1981;58 SupplS52. [6] Bennett PN. Phenobarbital. In: Bennett PN, editor. Drugs and human lactation. Amsterdam: Elsevier, 1988:329-30. [7] Kaneko S, Suzuki K, Sato T. et al. The problems of antiepileptic medication in the neonatalperiod: Is breast-feeding advisable? In: Janz D. et al., editors. Epilepsy, pregnancy and the child. New YorkRaven Press, 1982:343-7. [8] Hopkins A. Epilepsy and anticonvulsant drugs. Br Med J 1987;294:497-501. [9] Taddio A, Ito S. Drug use during lactation. In: Corhin G, editor. Maternal-fetal toxicology, a clinicians guide. seconded. New York: Dekker, 1994:113-219. [lo] Schou M, Amdisen A. Lithium and pregnancy-III, lithium ingestion by children breast-fed by women on lithium treatment. Br Med J 1973;288:138. [l l] Tyrala EE, Dodson WE. Caffeine secretion into breast milk. Arch Dis Child 1979;54:787-800. [12] Berlin CM, Denson HM, Daniel CH et al. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics 1984;73:59-63.
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[ 131 Davidson S, Alden L, Davidson l? Changes in alcohol consumption after childbirth. J Adv Nur\ 1981;6:195-8. [14] Mennella JA, Beauchamp GK. The transfer of alcohol to human milk. Effects on flavor and the infant’s behavior. New Engl J Med 1991;325:981-5. [15] Lawton ME. Alcohol in breast milk. Aust New Zealand .I Obstet Gynaecol 1985;25:71-3. 1161Kesaniemi YA. Ethanol and acetaldehydein the milk and peripheral blood of lactating women after ethanol administration. J Obstet Gynaecol Br Commonwealth 1974;81:84-6. 1171Buckalew LW. Effect of maternal alcohol consumption during nursing on offspring activity. Res Commun Psycho1Psychiatry Behav 1978;3:353-8. [ 181 Little RE, Anderson KW, EN-in CH et al. Maternal alcohol use during breast feeding and infant mental and motor development at one year. New Engl J Med 1989;321:425-30. [ 191 FinneganLP, O’Brien Fehr K. The effects of opiates, sedative-hypnotics,amphetamines,cannabisand other psycoactive drugs on the fetus and newborn. Gen Pharmacol 1976;119:653-723. [20] Smialek JE, Aronow R. Methadone deaths in children. J Am Med Assoc 1977;238:2516-7. [21] Bennett PN. Methadone. In: Bennett PN, editor. Drugs and human lactation. Amsterdam: Elsevier, 1988:319-20. [22] Chasnoff IJ, Lewis DE, Squires L. Cocaine intoxication in a breast-fed infant. Pediatrics 1987;80:836-8. [23] Woodward A, Miles H, Grgurinovich N. Cotinine in urine of smokers’ infants. Lancet 1984;i:935. [24] Woodward A, Grgurinovich N, Ryan P Breast feeding and smoking hygiene: Major influences on cotinine in urine of smokers’ infants. J Epidemiol Community Health 1986;40:309-15. [2SJ Dahlstrom A, Lundell B, Curvall M et al. Nicotine and cotinine concentrationsin the nursing mother and her infant. Acta Paediatr Stand 1990;79:142-7. [26] Labrecque M, Marcoux S, WeberJ-P et al. Feeding and urine cotinine values in babies whose mothers smoke. Pediatrics 1989;83:93-7. [27] Luck W, Nau H. Nicotine and cotinine concentrationsin serum and milk of nursing smokers. Br J Clin Pharmacol 1984;18:9-15. [ZS] Schulte-Hobein B, Schwartz-BickenbachD, Abt S et al. Cigarette smoke exposure and development of infants throughoutthe first year of life: Influence of passive smoking and nursing on cotinine levels in breast milk and infant’s urine. Acta Paediatr 1992;81:550-7. (291 Bisdom CJ. Alcohol and nicotine poisoning in infants. Mooandscrift voor Kindergeneeskunde 1937:85:332-41. [30] Majewski A. Clinical manifestation of nicotine intoxication in breast-fed infants. Wiad Lek 1979;32:275-7. [31] Richer C, Guidicelli JF. Excretion of drugs into human milk. Rev Med 1976;17:1149-57. [32] Vio F, Salazar G, Infante C. Smoking during pregnancy and lactation and its effects on breast-milk volume. Am J Clin Nutr 1991;54:1011-6. [33] Pollock II. A preliminary analysis of interactions between smoking and infant feeding. In: Poswillo D, Alberman E, editors. Effects of smoking on the fetus, neonateand child. Oxford: Oxford Medical Publications, 1992:108-20. 1341Needleman HL, JacksonRJ. Commentary: lead toxicity in the 21st century: will we still be treating it?. Pediatrics 1992;89:678-80. (351 Moore MR, Goldburg A, Pocock S et al. Some studies of maternal and infant lead exposure in Glasgow. Scott Med J 1982;27:113-22. [36] Ong CN, PhoonWO, Law HY et al. Concentrationsof lead in maternal blood, cord blood. and breast milk, Arch Dis Child 1985;60:756-9. [37] Harada M. Congenital Minamata disease:intrauterine methylmercury poisoning. In: Sever JL, Brent RL, editors. Teratogen update: Environmentally induced birth defect risks. New York: Alan R. Liss, 1986:123-6. [38] Baluja G, Hemandez LM, Gonzalez MJ et al. Presenceof organochlorine pesticides, polychlorinated biphenyls and mercury in Spainish human milk samples.Bull Environ Contam Toxic01 1982;28:571-7. [39] Zielhuis RL, Stijkel A, Verberk MM, Vande Poel-Bot M. Mercury. In: Zielhuis RL, Stijkel A, Verberk MM, editors. Health risks to female workers in occupational exposure to chemical agents. Berlin: Springer-Verlag, 1984:74-g.
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[40] Rogan WJ, Bagniewska A, Damstra T. Pollutants in breast milk. New Engl J Med 1980;302:1450-3. [41] Kuwabara K, Yakushiji T, Watanabe1 et al. Relationship between breast feeding and PCB residuesin blood of the children whose mothers were occupationally exposed to PCB’s. Int Arch Occup Environ Health 1978;41:189-97. [42] SavageEP.National study to determine levels of chlorinated hydrocarboninsecticidesin human milk: 1975-1976, and supplementary report to the national milk study: 1975-1976. Springfield, VA: National Technical Information Service, 1977. [43] SavageEP, Keefe TJ, Tessari JD et al. National study of chlorinated hydrocarbon insecticide residues in human milk, USA. Am J Epidemiol 1981;113:413-22. [44] Stacey CI, Perriman WS, Whitney S. Organochlorinepesticide residue levels in human milk: Western Australia, 1979-1980. Arch Environ Health 1985;40(2):102-8. 1451Rogan WJ, Gladen BC. Study of human lactation for effects of environmental contaminants: The North Carolina Breast Milk and Formula Project and some other ideas. Environ Health Perspect 1985;60:215-21. [46] Jacobson SW, Fein GG, Jacobson JL et al. The effect of intrauterine PCB exposure on visual recognition memory. Child Develop 1985;56:853-60. [47] Zieljuis RL, Stijkel A, Verberk MM, et al. Polychlorobiphenyls and polybromobiphenyls. In: Zieljuis RL, Stijkel A, Verberk MM, Van de Poel-Bot M, editors. Health risks to female workers in occupational exposure to chemical agents, 5. Berlin: Springer-Verlag, 1984:36-41. [48] Rogan WJ, Gladen BC, McKinney JD et al. Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk effects on growth, morbidity and duration of lactation. Am J Public Health 1987;77:1294-7. [49] JacobsonJL, Humphrey HEB, JacobsonSW et al. Determinantsof polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyl trichoroethane (DDT) levels in the sera of young children. Am J Public Health 1989;79:1401-4. [50] Schwartz EM, Rae WA. Effect of polybrominated biphenyls (PBB) on developmental abilities in young children. Am J Public Health 1983;73:277-80. [51] Gladen BC, Rogan WJ. Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichlomethene on later development. J Pediatr 1991;119:58-63. [52] Nerbert DW, Elashoff JD, Wilcox KR. Possible effect of neonatal polybrominated biphenyl, exposure on the development abilities of children. Am J Public Health 1983;73:286-9. [53] Lamplugh SM, Hendtickse RG, Apeagyei F et al. Aflatoxins in breast milk, neonatal cord blood, and serum of pregnant women. Br Med J 1988;296:968. [54] Peckham CS, Johnson C, Ades A et al. Early acquisition of cytomegalovirus infection. Arch Dis Child 1987;62:780-5. [55] Stagno S, Reynolds DW, Pass RF et al. Breast milk and the risk of cytomegalovirus infection. New Engl J Med 1980;302:1073-6. [56] Dworsky M, Yow M, Stagno S et al. Cytomegalovirus infection of breast milk and transmission in infancy. Pediatrics 1983;72:295-9. [57] Junker AK, Thomas EE, Radcliffe A et al. Epstein-Barr virus sheddingin breast milk. Am J Med Sci 1991;302:220-3. [58] Nakano S, Ando Y, Saito K et al. Primary infection of Japanese infants with adult T-cell leukaemia-associatedretrovirus (ATLV): Evidence for viral transmissionfrom mothers to children. J Infect 1986;12:205-12. [59] Lin H-H, Hsu H-Y, Chang M-H, Chen P-J, Chen D-S. Hepatitis B virus in the colostra of HBe Ag-positive carrier mothers. J Pediatr Gastmenterol Nutr 1993;17:207-10. [60] Ruff A, Coberly J, Halsey NA et al. Prevalence of HIV-l DNA and p24 antigen in breast milk and correlation with maternal factors. J AIDS 1994,7:68-73. [61] Palasanthiran P, Ziegler JB, Stewart GJ et al. Breast feeding during primary maternal human immunodeficiency virus infection and risk of transmission from mother to infant. J Infect Dis 1993;167:441-4. [62] Van de Perre P, Simonon A, Msellati P et al. Postnataltransmissionof human immunodeficiencyvirus type 1 from mother to infant. New Engl J Med 1991;325:593-8.
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1631 Hira SK, Mangrola UG, Mwale C et al. Apparent vertical transmission of human immunodelicienq virus type 1 by breast feeding in Zambia. J Pediatr 1990;117:421-4. 1641 Dunn DT, Newell ML, Ades AE et al. Risk of human immunodeficiency virus type 1 transmission through breast feeding. Lancet 1992;340:585-8. 1651 The Italian Register for HIV Infection in Children. Human Immunodeficiency Virus Type I infection and breast milk. Acta Paediatr Suppl 1994;400:51-8. [66] Datta P, Embree J, Kreiss J et al. Mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 1994;170:1134-40. [67] Hu DJ, Heyword WL, Byers RH et al. HIV infection and breast feeding: policy implications through a decision analysis model. AIDS 1992;6: 1505-13. [68] Ziegler JB. Breast feeding and HIV Lancet 1993;342:1437-8. 1691 Cutting WAM. Breast feeding and HIV in Africian countries. Lancet 1994;343:362. [70] A&up-Jensen A. Environmental and occupational chemicals. In: Bennett PN, editor. Drugs and human lactation. Amsterdam: Elsevier, 1988:55 l-73. 1711 Hergenrather J, Hlady G, Wallace B et al. Pollutants in breast milk of vegetarians. New En81 J Med 1981:26(March):792. 1721 Barr M. Environmental contamination of human breast milk. Am J Public Health I981 ;7 1: 124 -6.
Abstract It is welt recognised that although nutritionally breast milk is the optimal food for babies, there are a number of caveats to this, based on the consequences of the modern lifestyle. Here we have considered ways in which the young breast fed child may be exposed to various environmental and medical contaminants which might cause adverse reactions and to which he/she may not otherwise be exposed. These substances are divided into four different areas: (i) medication taken by the mother; (ii) exposure to possibly addictive drugs taken by the mother: (iii) exposure to pollutants mainly from the maternal diet or as the result of her occupation; (iv) viruses. The infant who consumes breast milk may be exposed to a variety ofchemicals which may have untoward effects on his/her immediate health and temperament and future development. Potentially hazardous substances ingested by the breast fed infant include medicaments (or their metabolites) that may have been ingested by the mother. potentially addictive common neurotoxicants such as nicotine, caffeine and alcohol, illicit drugs such as biphenyls and diheroin and cocaine, and pollutants such as polychlorinated chlorodiphenyltrichloroethane (DDT). There is a paucity of good information on which to base reliable estimates of the harm that this may cause the child. Although breast feeding is known to protect against bacterial infection, a number of viruses are excreted in the breast milk which may infect the child asymptomatically (e.g. cytomegalovirus, Epstein-Barr virus) and which are not known to be harmful, as well as human immunodeficiency virus (HIV) excretion which, in contrast, does appear to increase the risk of the child becoming infected. Balancing the risk of infection to the child born to an HIV infected mother, results in tie proposition that known HIV positive women in developing countries (where the risk of gastrointestinal infection is high) should continue to breast feed but those in the developed world (where the risk of gastrointestinal infection is lower) are better advised to bottle feed. 0 1997 Elsevier Science Ireland Ltd. Keywords:
Breast feeding: Medication; Addictive drugs; Pollutants: Viruses
0378-3782/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reservctl PII SO3?X-3782(97)00052-2
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1. Medication A study in Canada of 838 children who were being breast fed by mothers who were on medication of various sorts reported that 11.2% had minor adversereactions [I]. This proportion must be considered the tip of an iceberg since these were recognised adverse reactions with immediate demonstration. Identification of any long-term adverse outcome, not obviously related, could be more important but will certainly be more difficult to demonstrate. Of the minor adverse reactions identified, the three most common ones were: diarrhoea in the child due to antibiotics being taken by the mother; drowsiness associatedwith the mother’s intake of analgesics or narcotics and irritability associatedwith the mother’s exposure to antihistamine. Most drugs can be transmitted through breast milk to the infant [2]. Drugs administered to a lactating mother are passedby way of the epithelial cells of the mammary glands to the milk. The rate of diffusion of therapeutic agents across the mammary glands may be modulated by the physio-chemical properties of drug molecules. Thus, lipid-soluble drugs with low molecular weight pass through the membranein large amounts. Acidic drugs, such as barbiturates and benzyl penicillin, reach the milk less readily than alkaline drugs, such as erythromycin, antihistamines or alkaloids. The concentration of the drug in the milk depends on the dose administered, the duration of treatment, the daily quantity of milk secreted, the mother’s health, the mother’s drug tolerance and her genotype. Examples of drugs that may be harmful to the nursing infant have been listed below [2] with the adverse consequences in brackets: chloramphenicol (inhibition of bone growth), sulphonamides (jaundice), salicylates (disturbance of blood coagulation), paracetamol (methaemoglobinaemia), barbiturates (drowsiness, weak suck reflex), phenytoin (drowsiness, weakness),antidepressants(tremor, insomnia), anticoagulants (haemorrhage), steroid hormones (jaundice, disturbed bone growth) and thyroid hormones (hyperthyroidism). Given the freely available information about the numbers of drugs that reach the young infant via the breast milk it may seemsurprising that in the maternity hospital drugs are freely administered to women who have just delivered but intend to breast feed. In Norway [3] a study of 970 women delivered vaginally in five hospitals showed that 90% had received drugs; this excluded from consideration laxatives, oxytocics, vitamins and iron as well as long-term medication. The drugs that were given to the mothers included hypnotics (86% of mothers) and analgesics(65-95%). The author comments that the frequent use of hypnotics indicates that breast feeding mothers were treated like ordinary hospital patients rather than mothers about to breast feed a young infant. She noted that for most of the drugs used routinely on the post-natal wards there was little or no data on excretion in breast milk upon which to base any judgement about the appropriatenessof prescription. The commonly used drugs are the most worrying in regard to effects on the child, since if there are adverse consequences,large numbers of children may be affected.
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Aspirin is freely taken by large numbers of women, and yet has been banned from administration to young children because of substantial evidence linking it with Reye’s Syndrome. Nevertheless,mothers expose their child to aspirin in breast milk without realising that this may be equivalent to giving aspirin to their baby. Although it is generally thought unlikely [4] that a single dose of aspirin will result in a high dose to the young breast fed child, salicylate will be present in the milk of mothers who are on long-term high dose salicylate therapy. One child, for example, was shown to have very high plasma levels while being breast fed by a mother who was receiving 2.4 g of aspirin per day. In this situation there is a significant risk of both kernicterus and intracranial haemorrhage [51. Phenylbarbitone is a barbiturate used formerly as a sedativebut currently mainly as an anticonvulsant. One study of 42 breast fed infants of epileptic mothers who were on this medication, was reported to show poor weight gain and a high incidence of vomiting and inadequate suckling [6]. Although this report was written with authority, on returning to the actual paper cited, the 42 infants were not, in fact, all exposed to breast milk let alone to phenylbarbitone. Only thirteen of the children were breast fed and phenytoin, primidone and carbamazepinewere taken by some of the mothers rather than phenylbarbitone. It is therefore very difficult to identify the adverse effects of a particular drug. The authors did show, however, that the breast fed group lost weight in the first five days when compared with the bottle fed or control groups of children [7]. A casereport of one child who died while being breast fed by an epileptic mother taking phenylbarbitone showed a very high level of phenylbarbitone in the infant’s blood. It was concluded [6] therefore that it is unsafe for a mother to continue to take this drug while breast feeding. However, a review of the literature published in 1987 [S] stated that “most mothers taking anticonvulsant drugs may safely breast feed their children”. This was despite the author noting that significant amounts of the drugs do pass into the milk. The ratio of the drug content of breast milk to the serum level of the mother was given as 19% for phenytoin, 41% for carbamazepine,36% for phenylbarbitone and 70% for primidone. The samestudy of 42 children 17) quoted before is used to reach a substantially different conclusion. It is therefore obvious that not enough is known about anticonvulsants and their effecr via breast milk on susceptible children. Other substancesthought to have an effect on the developing infant are antidepressants and tranquilisers. Benzodiazepinesmay cause problems since the metabolising ability of the young baby may be impaired and the drugs accumulate in the susceptible infant [9]. One study of the antidepressantlithium [lo] showed that the breast fed child of a mother consuming this drug had detectablelevels in the serum, especially in the first two weeks of life. The authors suggestedthat “Arguments can be presented both for and against the view that a lithium treated woman should be permitted to breastfeed her child. On the one hand during the pregnancy the child has been exposedto the samelithium concentration as the mother for many months and it seemsunlikely that exposure to a lower lithium concentration for a few more months will do any harm. On the other hand any unnecessary ingestion of drugs is undesirable and potentially dangerous”.
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2. Exposure to possibly addictive drugs 2.1. Caffeine
Caffeine is consumed by many women. Currently there is no advice to breast feeding mothers about the possible effects of high caffeine consumption on the breast fed infant. The studies concerning the ingestion of caffeine during breast feeding are very limited. One [ 1l] studied five breast feeding mothers and observedthe results of a standardisedoral dose of caffeine. It was shown that caffeine does not diffuse freely and that the concentrations in breast milk are lower than in maternal serum. The authors suggestedthat the breast fed infant would receive only a low dose of caffeine after the mother had drunk a single cup of coffee but with repeated maternal ingestion, the caffeine would accumulate, depending on the rate of elimination in young infants. A further study [12] of fifteen mothers who were given a single dose of caffeine showed that in eleven of these the caffeine was excreted in the breast milk but no caffeine was found in any of the children’s urine samples.However, there was substantial data suggesting that caffeine metabolism differed in each of the women resulting in different levels in the breast milk. It is possible that children are not exposed to significant dosesof caffeine from the breast milk if the mother consumes relatively small amounts-but caffeine in the breast milk of a high consumer may be more significant. 2.2. Alcohol
Nursing mothers are frequently advised to take alcohol containing drinks on the understanding that this helps in the breast feeding process by relaxing them and aiding the ‘let down reflex’ [ 131. Although experienced breast feeders are often convinced that this enablesthe child to be more readily fed, there is no real evidence of this. It is now well-established [14] that the alcohol drunk by a nursing mother affects the odour of the milk and the feeding behaviour of the infant. Although the young child sucks more frequently during the first minute of breast feeding after the mother has had an alcohol containing drink, he/she consumessignificantly less breast milk during such a feed [ 141.The ethanol is excreted in the breast milk and is there in a similar concentration to that found in the peripheral blood of the mother [ 15,161. Nevertheless,the amount of alcohol that a breast fed child could receive is thought to be relatively low and unlikely to causeharmful effects if the maternal use of alcohol is temperate [ 161. The key question concerns whether the alcohol intake in breast milk can have an adverse effect on the developing child. One study has shown that mice exposed to alcohol in breast milk are substantially less active comparedwith unexposed,control new-born mice [17]. The one major study of alcohol exposure via breast milk on the developing human [ 181 suggestedthat alcohol ingested via breast milk had a slight but significant detrimental effect on motor development though not on mental development. This finding has not yet been tested in any other study. Until that has
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been done, it may be safer to suggestthat alcohol ingestion of anything other than a small amount should be avoided during breast feeding. 2.3. Illicit
drugs
When illicit drugs are taken they are usually continued throughout pregnancy and thereafter. Consequently it is difficult to untangle adverseeffects due to exposure via breast milk from the long-term results of exposure in utero. It is certainly true that a baby who would otherwise experience withdrawal effects during the early neonatal period, is less likely to do so if breast fed by a mother who is continuing to take the particular drug to which the child had been exposed in utero [ 191.Opiates, including morphine, heroin and methadoneare detectablein breast milk after maternal use, but the total amounts excreted are thought to be small. Methadone ingested in breast milk, however, may have contributed to the death of at least one infant [ZO]. In spite of this, the current recommendation [21] is that the risk to the suckling infant of ir mother taking methadone would appear to be low on the basis that the quantity of drugs that appearsin breast milk is small. Breast feeding is recommendedproviding the maternal dose is low and the mother is warned to seek medical advice if her child appearssedated. Cocaine has not yet been studied fully. Nevertheless there is a useful case report [22J of a two week old infant girl whose mother, having avoided cocaine in the last seven months of pregnancy, used some cocaine with the result that the child had a major outburst responsewith marked neurological problems which were transient in nature. In this case levels of cocaine were found in the maternal milk for as long as 36 hours after she had used it. It seemslikely therefore that children of breast-feeding cocaine using mothers would be adversely affected. The effects of cannabis on the breast fed child have not been studied. However, on the basis that data concerning cannabis intake during pregnancy have shown little in the way of long-term adverse effects, there is a possibility that breast feeding while using cannabis may not have major detrimental consequences,but further studies of this are awaited. 2.4. Cigurette smoking
There is now substantial evidence to show that smoking mothers who breast feed are exposing their children to cotinine and nicotine with a concentration of up to I 14 mg/l ]23]. That this is absorbedby the infant is shown by a number of studies. For example, a study in Australia [24] of 79 infants whose mothers were current smokers showed a linear relationship between the number of cigarettes smoked and the cotinine level in the infant’s urine (r = 0.79, P
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in the mother’s plasma. There was a striking difference in exposure of the infant according to whether the mother had smoked shortly before breast feeding. In Canada 33 infants whose mothers smoked were studied [26]. The correlation coefficient between the number of cigarettes smoked by the mother and the breast milk cotinine concentration was statistically significant (r = 0.69, P = 0.0002). Similarly the urinary cotinine of the babies increasedwith the cotinine levels in the mother’s milk (I = 0.56, P = 0.02). In Germany, [27] a study of 23 nursing mothers showed a linear correlation between nicotine in the serum and nicotine in the milk (r = 0.70) and again that the nicotine concentrations in milk were 2.9 times higher than the corresponding serum concentrations. Similarly there was a linear correlation between cotinine concentrations in the serum and in the milk (r = 0.89). A further study from Germany was concerned with 69 infants whose mothers smoked more than five cigarettes a day [28]. Those who were breast fed had urinary levels that were in the same range as adult smokers would have been. The major question concerning nicotine and cotinine in breast milk is whether this has a detrimental affect on the child. One of the earliest publications [29] related a casehistory of a six week old infant whose mother smokedtwenty cigarettesper day. Symptoms of restlessness, insomnia, vomiting, diarrhoea, rapid pulse etc., disappearedonce the mother stoppedbreast feeding her infant. In a study of four cases of so-called ‘nicotine intoxication’ occurring at three to four days of age [30], the babies refused to suck further, vomited after feeding, their skin appeared grey in colour, and they becameapathetic and flaccid. After the mothers stoppednursing the symptomsdisappeared.A further study published in 1976 [3 l] reported the symptoms of nicotine ingestion as being nausea,vomiting and diarrhoea. We show elsewhere that women who smoke are less likely to breast feed and also that once breastfeeding they are more likely to give up earlier than non-smokers.One study has looked at the volume of breast milk in smoking as opposedto non-smoking mothers [32]. A comparison of ten smokers with ten non-smokers showed that the non-smoking mothers had significantly greater breast milk volume (961 g per day) than smoking mothers (693 g/day, P < 0.001). Not surprisingly the growth of the infants of the non-smoking mothers was also greater, 550 g per fourteen days, compared with 340 g (P
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development of an intellectually sub-normal child. Nevertheless, it must be stressed that further studies are needed before too much weight can be given to this result.
3. Inadvertent exposures--pollutants 3.1. Heavy metals
Heavy metals are important in that they can have major detrimental effects on the developing brain of the young child. It has been established, for example, that increasing lead exposure results in a marked decrease in IQ level. There is no threshold effect, and the only truly safe level is zero [34]. There is, however, little evidence that lead appears substantially in breast milk. Breast milk contains only a small fraction of the mother’s blood levels [35), however, there is a significant positive correlation between the two. In Malaya, a study of 114 subjects found a correlation of 0.29 (Z’ < 0.01) between maternal blood levels and breast milk levels of lead [36]. Mercury too, results in neurological damage. Once taken up the methyl mercury remains in the brain for a considerable period of time, and symptoms may progress over a long period [37]. The most convincing data on the adverseeffects of mercury come from the unfortunate Minamata area of Japan. Mothers accidentally exposed during pregnancy and lactation produced high levels of fetal and infant abnormal brain development. The methyl mercury concentration in the mother’s milk was 3-6% (63 mg/l) of that in their blood [373. In less extreme casesdetectablelevels of mercury have been found in breast milk. In Spain [38], for example, the concentration was 9.5 mg/l, but it is not known if this level is harmful to the infant. The neonateof an exposedmother will be born with an increasedbody burden, mostly concentratedin its brain, and then lactation will add au extra load. As with lead, the infant’s developing nervous system is much more susceptible to mercury than the fully developed nervous system would be [39]. 3.2. Pesticides and other organochlorine
compounds
The most worrying pollutants in terms of breast feeding are the organohalidessuch as polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs) and dichlorodiphenyltrichloroethane (DDT). DDT and its metabolite DDE (dichiorodiphenyldieldrin) were used widely as pesticides in the 1950s and 1960s. The detectable levels of DDT and DDE in breast milk were noted as early as 195I. Although no longer used in the West, DDT is still used in many developing countries and therefore is found in products, such as cigarette tobacco, grown in those countries. All organohalides are resistant to physical degradation and biologic metabolism and are widespreadin the environment. Once ingested they are stored in fat tissue and unlikely to be excreted unless through breast milk. Thus lactation is the only way in which a mother is likely to get rid of substantial amounts of these
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substances.This may improve her health, but will passthe burden to the tissuesof the young infant [40]. Studies in Japanof women occupationally exposedto PCBs found that there was a positive correlation between the length of time their children had been breast fed and the PCB levels in the child’s blood [41]. In 1975, in the USA, 1038 breast milk sampleswere analysedfor PCBs. Only 1% had no contamination and 30% had levels above 0.05 ppm [42]. A later study from the USA looked at other hydrocarbon insecticide residues in human milk and found that evidence of contamination with dieldrin, heptochlorepoxide and oxychlordane was substantial and varied significantly between different areas within the USA [43]. A study from Australia in 1979/1980 showed that levels of organochlorine pesticides in breast milk were positively related to maternal age-the older the mother the higher the levels [44]. A major study in North Carolina [45] showed no relationship, however, between the mother’s age, race, occupation or cigarette smoking and PCBs, but did find that regular alcohol use was associated with somewhathigher levels of PCBs in breast milk. DDE on the other hand did increase with age and was higher in blacks and in smokers. This study found that the concentration of PCBs and DDE in breast milk declined with the continuing course of lactation with values at six months about 20% less than those at the beginning of lactation. A study from Michigan showed that fish consumption was correlated with PCB levels in maternal serum and maternal milk. It showed that these levels increased with age, but were not related to social class, parity or body weight [46]. The key question is whether these chemicals have any adverseeffects on the young child. It has been suggestedthat health risks to the offspring are greater for exposures during lactation than during pregnancy [47]. In the short-term, however, the North Carolina study [48] showed no effect on growth or morbidity. In Michigan, levels of PCBs, PBB and DDT in the young child were obtained at four years of age. The length of time the child had been breast fed was the most important determinant of its burden of these chemicals [49]. One study from the USA looked at eighteen children aged four to six who had been exposed to PBB in utero and/or through breast milk. In comparison with normative test data, those children exposed to PBBs were within the normal range in all areas assessed.Nevertheless, within the children, the amount of PBB stored in fat was shown to be inversely related to some of the developmental scores [50]. The North Carolina cohort were examined at ages two, three, four and five and, although at two years, the Bailey scalesappearedto show deficits in the children who had been most exposed, no such differences were found in later childhood [51]. As Nebert et al. stated [52] “Since man is at the end of the food chain, persistence of heavily halogenated PCBs and PBBs appears to be with us at least for the foreseeable future.... breast feeding by PCB contaminated mothers will lead to an enhancedingestion of PCBs in these infants from birth. This transfer of PCBs from one generation to the next is also occurring with PBBs. It therefore should be emphasisedthat one should be on the look out, at least for the next several decades, for numerous possible clinical effects-including subtle changesin intelligence and long-range effects causing cancer in PCB exposed and PBB exposed individuals”.
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3.3. Other pollutants Very little data concerning other pollutants is currently available. There are. however, reports of atlatoxin excretion in breast milk of mothers in Africa [53]. The authors warn that given the adverse effects of such exposure in controlled animal experiments (where immunity, liver function, nutrition and survival were affected). the possible long-term consequencesof exposure of the infant as a result of a&toxin ingestion by the mother, should be considered seriously.
4. Viruses
Although much research into the protective effect of breast milk in relation to various infective organisms has been undertaken, less concern has been expressed over possible viral transmission through breast milk. Studies have shown, however, that cytomegalovirus (CMV) infection is transmitted through breast milk. One London group followed 253 infants from birth for twelve months, with urine samples being collected at birth, six weeks, three months, eight months and one year. Of the women, 123 were sero-positive and 33% of their children acquired CMV after the first week of life. The risk of the sero-positive mothers passing the infection to their child was greatly increased if they were breast fed. Among the 64 infants who were breastfed for longer than twelve weeks, 42% becameinfected; of those breastfed for less than twelve weeks, 30% became infected, whereas only 19% of those who did not breast feed at all became infected [54]. CMV infection acquired in this way is seldom symptomatic, although it has been associatedwith pneumonitis. Similar results were found in the USA [55], where a study of the breast milk of 41 sero-positive women showed that 69% of those for whom CMV was identified in the breast milk had infants who became infected compared with 10% of those whose milk did not appearto have the virus present. Mothers who breast fed their infant fat one month or longer were more likely to pass the infection to their child than those who stopped breast feeding within one month [56]. Another herpes virus, the Epstein-Barr virus (EBV) is also shed in breast milk. A study in British Colombia took breast milk samples from 100 randomly selected women and assayedfor virus particles. Forty-six percent had EBV cells in the breast milk [57]. It was found that the EBV was more likely to be shed in breast milk as lactation proceeded,and that excretion was intermittent. The authors suggestedthat a substantial proportion of infants would be infected with EBV by this route. Certainly. it is well-known that a high proportion of children are infected with EBV in their first two years of life, and breast milk seemsa likely route. A further virus that has been reported present in breast milk is the adult T-cell leukaemia virus (ATLV), which has been reported from Japan. There, when breast milk samples were infected with ATLV, 81% of the infants who were breast fed became infected in the post-natal period [58]. Studies from Taiwan have implicated potential transmission of the hepatitis B virus (HBV). They showed the presence of HBV-DNA in colostrum from 50 carrier
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mothers and suggestedthat all babies born to such mothers should be vaccinated against HBV at birth [59]. The major discussion point concerning viral transmission, however, concerns human immunodeficiency virus (HIV). The HIV virus has certainly been detectedin breast milk [60]. Evidence that children of breast feeding mothers becomeinfected by HIV becauseof exposure via breast milk comesfrom two separategroups of studies. The first comprises a small number of instances where the mother appearsto have become infected after delivery and the presumed source of infection in the child has been the breast milk. This included ten women in Australia who received infected blood products after delivery-two of the ten breast fed children became infected [61]. In Rwanda, sixteen infants were born to mothers who sero-converted after delivery-nine of these became infected, but it was thought that five of the infants were probably infected during pregnancy or delivery. Considering only the women who sero-convertedat least four months after delivery, four of the ten infants became infected [62]. A third study in Zambia identified nineteen women who sero-converted in the year following delivery-three of the breast fed children becameinfected [63]. The other set of studies considers women who were infected during pregnancy and the incidence of infection in their children comparing those who were breast fed and those who were bottle fed. A meta-analysisof six prospective studies [64] showed an excessrisk of transmission in the breast fed group of about 14% (95% CI, 7-22%). Subsequently a large Italian study improved interpretation of the findings by controlling for potential confounding factors including gestation, birthweight, mode of delivery and maternal drug addiction [65]; the adjusted odds-ratio for breast feeding (versus formula feeding) was 2.55 [95% CI, 1.03-6.371. A study from Kenya [66] followed 365 children whose mothers were infected with HIV-l and showed that two factors only were predictive of sero-conversion-marriage and prolonged breast feeding-of fifteen months or more. There was no comparisonwith a never breast fed group-presumably becauseall babies were breast fed. Much discussion, therefore, has taken place with regard to the pros and cons of an HIV infected mother breast feeding her child. Whereasin the developedworld where artificial feeding appearsto have little effect on infant mortality, the choice seems clear-a mother who is clearly infected should be advised not to breastfeed the child, in the developing world, the balance of risks are by no means clear. Statistical techniques have been used to try to devise appropriate decision trees indicating the circumstances in which an infected mother should be advised to breast rather than bottle feed. The models, however, rely on a valid estimate of the relative risk of infant death associatedwith bottle feeding. As we have shown, this is not a statistic that is easily come by. A study by Hu et al. [67] suggestedthat, if the under five mortality rate for breast fed infants is 25%, and the relative risk associatedwith bottle feeding is 3, the post-natal transmission rate associatedwith breast feeding should be at least 67% before bottle feeding should be advised. Again, if the excessmortality is 10% and the increased risk associatedwith bottle feeding is 2%, then bottle feeding should be advised if the post-natal infection risk from breast feeding is in excess of 10%. As pointed out in correspondence,however [68], the situation is far more complex, since in developing countries the women rarely knows her HIV status.
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Cutting [69] points out the other major problem in recommending artificial feediag--the cost. This can be as much as nine times the daily wage of a hospital cleaner in Uganda. Clearly discussion of priorities is needed in this situation and this should take place at high level. 5. Discussion “Man is exposed to innumerable chemicals from sources in the natural environ-. ment and the work place. Some of these chemicals especially the lipophiiic and persistent organohalogenssuch as DDT, PCB and the dioxins accumulate in human fat tissues and are excreted mainly by breast milk. Human milk in general contains 10-50 more of these contaminants than do cows’ milk or milk substitutes: even though the period of breast feeding is short in comparison to a life time, these chemicals persist in the body and enter it at a sensitive phase of its development. There should be a constant awarenessof this source of potential toxic substancesfor the breast fed infant.” [70]. The question of how mothers should cope with this threat is unresolved. There is some evidence that eliminating animal products from the diet may be useful in reducing the level of contaminants in the breast milk. A study of twelve vegetarian women who consumed no animal products for religious reasonsfound the levels of sixteen of seventeenmeasuredcontaminantsin their breastmilk to be lower than that in the milk of typical American women. The one group of pollutants which were at similar levels to the rest of the country, however, were the PCBs 2711.In a review published in 1981, Barr [72] stated that “Human breast milk is decidedly the preferred food for human infants and breast feeding is the preferred method of feeding. On the other hand it should be recognised that formula feeding by bottle is widely accepted as an alternative with apparent safety and good results in the majority of cases. There are circumstances in which formula feeding may be necessary or even desirable. The question is does contamination of breast milk constitute a reason to discourage breast feeding?” This begs the question whether breast feeding with contaminated milk produces adverse consequencesin the infant. He goes on to say “In the current situation we can opt for one of two extremes or choose some spot in the middle ground. It has been advised that mothers with burdens of polyhydrogenated biphenyls or other environmental contaminants do not breast feed at all. This certainly would avoid adding to the body burden of the infant who had already been transplacentally exposed. However, such advice, if taken. would mean that few mothers would breast feed their infants since virtually all mothers have contaminants in their milk, mainly at levels above those permitted by law in other food stuffs”. Although he wrote in 1981, the question as to whether heavily contaminated mothers should be identified and advised not to breast feed i> still under debate. Far more important probably, are the exposures of the infant to those potentially addictive drugs, nicotine and cotinine, ethanol and the illicit drugs particularly cocaine, heroin and other opiates. A question must also be raised about the common
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medications taken by mothers. Is consideration ever given to whether tests have been done on breast milk to assessthe amount of a drug or its metabolites that reach the young child, and what effect they might have? Mothers should be made far more aware of the potential problem of consuming any of these substanceswhile breast feeding. A smoking mother currently believes she is protecting her child if she goes outside to smoke, but does not realise that the smoke inhalation by the child is not the only adverseeffect that might occur if she is breast feeding. A mother who is taking medication of various sorts rarely considers whether this may affect her breast fed infant and yet most drugs are excreted into the breast milk with consequenceslargely uncharted [9]. In general there are a number of different preparations available for a given maternal condition, and thus information on the optimum medication for the breast fed baby should be available. Much of the current advice on breast feeding and medication is based on information concerning the levels of drug in the breast milk as opposed to the maternal serum, and the relationship of the dose to the baby in relation to the therapeutic dose. This begs the question of the possible adverse reactions of a baby in receipt of low levels of a medication for which there are no immediate indications. In these circumstancesit is unlikely that the baby will reap any benefits.We would concur that “further research is urgently neededto determine maternal medications safe for nursing infants” [71]. References [l] Ito S, Blajchman A, StephensonM et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am .I Obstet Gynecol 1993;168:1393-9. 121Basu TK. Nutritional factors and dispositions of pharmacological chemicals in prenatal and neonatal life. In: Kacew S, Lock S, editors. Toxicologic and pharmacologic principles in pediatrics. New York: Hemishere, 1988:17-40. [3] MathesonI. Drugs to mother and infant in the maternity ward. A survey at five university hospitals in Norway. Saertrykk av Tidsskrift for Den Norske Laegeforening Nr22 1989;109:2118-22. [4] Brooks PM, Needs CJ. NSAIDS in lactating women. In: Famaey JP,Paulus HE, editors. Therapeutic applications of NSAIDS: subpopulations and new formulations. New York Marcel Dekker, 1992:157-62. [5] Rumack CM, Guggenheim MA, Rumack BH et al. Neonatal intracranial haemorrhageand maternal use of aspirin. Obstet Gynecol 1981;58 SupplS52. [6] Bennett PN. Phenobarbital. In: Bennett PN, editor. Drugs and human lactation. Amsterdam: Elsevier, 1988:329-30. [7] Kaneko S, Suzuki K, Sato T. et al. The problems of antiepileptic medication in the neonatalperiod: Is breast-feeding advisable? In: Janz D. et al., editors. Epilepsy, pregnancy and the child. New YorkRaven Press, 1982:343-7. [8] Hopkins A. Epilepsy and anticonvulsant drugs. Br Med J 1987;294:497-501. [9] Taddio A, Ito S. Drug use during lactation. In: Corhin G, editor. Maternal-fetal toxicology, a clinicians guide. seconded. New York: Dekker, 1994:113-219. [lo] Schou M, Amdisen A. Lithium and pregnancy-III, lithium ingestion by children breast-fed by women on lithium treatment. Br Med J 1973;288:138. [l l] Tyrala EE, Dodson WE. Caffeine secretion into breast milk. Arch Dis Child 1979;54:787-800. [12] Berlin CM, Denson HM, Daniel CH et al. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics 1984;73:59-63.
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[40] Rogan WJ, Bagniewska A, Damstra T. Pollutants in breast milk. New Engl J Med 1980;302:1450-3. [41] Kuwabara K, Yakushiji T, Watanabe1 et al. Relationship between breast feeding and PCB residuesin blood of the children whose mothers were occupationally exposed to PCB’s. Int Arch Occup Environ Health 1978;41:189-97. [42] SavageEP.National study to determine levels of chlorinated hydrocarboninsecticidesin human milk: 1975-1976, and supplementary report to the national milk study: 1975-1976. Springfield, VA: National Technical Information Service, 1977. [43] SavageEP, Keefe TJ, Tessari JD et al. National study of chlorinated hydrocarbon insecticide residues in human milk, USA. Am J Epidemiol 1981;113:413-22. [44] Stacey CI, Perriman WS, Whitney S. Organochlorinepesticide residue levels in human milk: Western Australia, 1979-1980. Arch Environ Health 1985;40(2):102-8. 1451Rogan WJ, Gladen BC. Study of human lactation for effects of environmental contaminants: The North Carolina Breast Milk and Formula Project and some other ideas. Environ Health Perspect 1985;60:215-21. [46] Jacobson SW, Fein GG, Jacobson JL et al. The effect of intrauterine PCB exposure on visual recognition memory. Child Develop 1985;56:853-60. [47] Zieljuis RL, Stijkel A, Verberk MM, et al. Polychlorobiphenyls and polybromobiphenyls. In: Zieljuis RL, Stijkel A, Verberk MM, Van de Poel-Bot M, editors. Health risks to female workers in occupational exposure to chemical agents, 5. Berlin: Springer-Verlag, 1984:36-41. [48] Rogan WJ, Gladen BC, McKinney JD et al. Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk effects on growth, morbidity and duration of lactation. Am J Public Health 1987;77:1294-7. [49] JacobsonJL, Humphrey HEB, JacobsonSW et al. Determinantsof polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyl trichoroethane (DDT) levels in the sera of young children. Am J Public Health 1989;79:1401-4. [50] Schwartz EM, Rae WA. Effect of polybrominated biphenyls (PBB) on developmental abilities in young children. Am J Public Health 1983;73:277-80. [51] Gladen BC, Rogan WJ. Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichlomethene on later development. J Pediatr 1991;119:58-63. [52] Nerbert DW, Elashoff JD, Wilcox KR. Possible effect of neonatal polybrominated biphenyl, exposure on the development abilities of children. Am J Public Health 1983;73:286-9. [53] Lamplugh SM, Hendtickse RG, Apeagyei F et al. Aflatoxins in breast milk, neonatal cord blood, and serum of pregnant women. Br Med J 1988;296:968. [54] Peckham CS, Johnson C, Ades A et al. Early acquisition of cytomegalovirus infection. Arch Dis Child 1987;62:780-5. [55] Stagno S, Reynolds DW, Pass RF et al. Breast milk and the risk of cytomegalovirus infection. New Engl J Med 1980;302:1073-6. [56] Dworsky M, Yow M, Stagno S et al. Cytomegalovirus infection of breast milk and transmission in infancy. Pediatrics 1983;72:295-9. [57] Junker AK, Thomas EE, Radcliffe A et al. Epstein-Barr virus sheddingin breast milk. Am J Med Sci 1991;302:220-3. [58] Nakano S, Ando Y, Saito K et al. Primary infection of Japanese infants with adult T-cell leukaemia-associatedretrovirus (ATLV): Evidence for viral transmissionfrom mothers to children. J Infect 1986;12:205-12. [59] Lin H-H, Hsu H-Y, Chang M-H, Chen P-J, Chen D-S. Hepatitis B virus in the colostra of HBe Ag-positive carrier mothers. J Pediatr Gastmenterol Nutr 1993;17:207-10. [60] Ruff A, Coberly J, Halsey NA et al. Prevalence of HIV-l DNA and p24 antigen in breast milk and correlation with maternal factors. J AIDS 1994,7:68-73. [61] Palasanthiran P, Ziegler JB, Stewart GJ et al. Breast feeding during primary maternal human immunodeficiency virus infection and risk of transmission from mother to infant. J Infect Dis 1993;167:441-4. [62] Van de Perre P, Simonon A, Msellati P et al. Postnataltransmissionof human immunodeficiencyvirus type 1 from mother to infant. New Engl J Med 1991;325:593-8.
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1631 Hira SK, Mangrola UG, Mwale C et al. Apparent vertical transmission of human immunodelicienq virus type 1 by breast feeding in Zambia. J Pediatr 1990;117:421-4. 1641 Dunn DT, Newell ML, Ades AE et al. Risk of human immunodeficiency virus type 1 transmission through breast feeding. Lancet 1992;340:585-8. 1651 The Italian Register for HIV Infection in Children. Human Immunodeficiency Virus Type I infection and breast milk. Acta Paediatr Suppl 1994;400:51-8. [66] Datta P, Embree J, Kreiss J et al. Mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 1994;170:1134-40. [67] Hu DJ, Heyword WL, Byers RH et al. HIV infection and breast feeding: policy implications through a decision analysis model. AIDS 1992;6: 1505-13. [68] Ziegler JB. Breast feeding and HIV Lancet 1993;342:1437-8. 1691 Cutting WAM. Breast feeding and HIV in Africian countries. Lancet 1994;343:362. [70] A&up-Jensen A. Environmental and occupational chemicals. In: Bennett PN, editor. Drugs and human lactation. Amsterdam: Elsevier, 1988:55 l-73. 1711 Hergenrather J, Hlady G, Wallace B et al. Pollutants in breast milk of vegetarians. New En81 J Med 1981:26(March):792. 1721 Barr M. Environmental contamination of human breast milk. Am J Public Health I981 ;7 1: 124 -6.