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CORK Bibliography: Breast Feeding

54 citations. January 1996 to present

Prepared: June 2007

Abdel-Latif ME; Pinner J; Clews S; Cooke F; Lui K; Oei J. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 117(6): E1163-E1169, 2006. (30 refs.)

OBJECTIVE. The purpose of this research was to assess the effects of breast milk on the severity and outcome of neonatal abstinence syndrome. METHODS. We conducted a retrospective chart review of 190 drug-dependent mother and infant pairs. Patients were categorized according to the predominant type of milk consumed by the infant on the fifth day of life (breast milk: n = 85 or formula: n = 105). The Finnegan's scoring system was used to monitor withdrawal, and medication was commenced if there were 2 scores of >= 8. RESULTS. Mean Finnegan scores were significantly lower in the breast milk group during the first 9 days of life even after stratifying for prematurity and exposure to polydrug and methadone. Significantly fewer infants required withdrawal treatment in the breast milk group. The median time to withdrawal occurred considerably later in breast milk group. In a multivariate analysis controlled for exposure to drugs of high risk of neonatal abstinence syndrome, polydrug, and prematurity, breast milk group was associated with lower need for neonatal abstinence syndrome treatment. CONCLUSIONS. Breast milk intake is associated with reduced neonatal abstinence syndrome severity, delayed onset of neonatal abstinence syndrome, and decreased need for pharmacologic treatment, regardless of the gestation and the type of drug exposure.

Alm B; Lagercrantz H; Wennergren G. Stop SIDS: Sleeping solitary supine, sucking soother, stopping smoking substitutes. Acta Paediatrica 95(3): 260-262, 2006. (23 refs.)

The recognition of prone sleeping and maternal smoking as modifiable risk factors for sudden infant death syndrome (SIDS), has drastically decreased SIDS incidence. However, during the last years other factors have become necessary to consider to further reduce the risk of SIDS. Side sleeping implies a greater risk than supine sleeping but is still common. Bed sharing may increase the risk of SIDS, while use of a pacifier seems to be protective. Replacement of maternal smoking with nicotine substitutes is not harmless. Conclusion: To further reduce the risk of SIDS, exclusive supine sleeping should be encouraged and side sleeping discouraged. When the breast-feeding is established, a pacifier can very well be used at bedtime. Bed sharing can increase the risk of SIDS if the infant is below 2-3 months of age, especially if the mother is a smoker. Any nicotine use should be avoided during pregnancy and breast-feeding.

Alvik A; Haldorsen T; Lindemann R. Alcohol consumption, smoking and breastfeeding in the first six months after delivery. Acta Paediatrica 95(6): 686-693, 2006. (31 refs.)

Aim: To study alcohol use and smoking after delivery, and to relate this to breastfeeding. Methods: A longitudinal questionnaire study, representative of pregnant women in Oslo. Ninety-two per cent agreed to join the study. Non-Norwegian speaking and/or immigrants from non-western countries were not invited. Questionnaires were answered at 17 (T1) and 30 (T2) wk of pregnancy, and 6 mo after term (T3). They were completed by 93% (1749 women) at T1, 82% at T2, and 92% at T3. Results: Six months after delivery, 80% reported alcohol use. The mean alcohol consumption per week was less than half compared to the last 6 mo before pregnancy. The women with the highest pre-pregnancy use reduced the most. Binge drinking (>= 5 drinks) was also reported by half as many women (29%). However, 6% reported 12 or more drinks per occasion at least once. No demographic or mental health variables predicted binge drinking after pregnancy. Smoking 6 mo after pregnancy was reported by 18%, a reduction of 50% from before pregnancy. Women breastfeeding for at least 6 mo had higher education, less frequently reported binge drinking after delivery and less frequently suffered postnatal depression. Conclusion: In this population-based sample were 86% breastfed for at least 6 mo, the level of binge drinking is concerning.

Amir LH; Donath SM. Does maternal smoking have a negative physiological effect on breastfeeding? The epidemiological evidence. Birth Issues in Perinatal Care 29(2): 112-123, 2002. (93 refs.)

Background: Women who smoke are less likely to breastfeed their children than nonsmokers. It is thought that nicotine has a negative effect on breastmilk supply by suppressing prolactin levels. The aim of this review was to assess the epidemiological evidence that maternal smoking has a negative physiologieal effect on breastfeeding. Methods: The following data sources were searched: The Cochrane Library, Medline, CINAHL, Current Contents, Psychinfo, Sociological Abstracts and the Lactation Resource Centre (Australian Breastfeeding Association) using the keywords "smoking" and "breastfeeding" or "infant feeding." The Journal of Human Lactation and Birth were hand searched. Results: Women who smoke are less likely to intend to breastfeed, less likely to initiate breastfeeding, and likely to breastfeed for a shorter duration than nonsmokers. Several studies have found a dose-response relationship between the number of cigarettes smoked each day and breastfeeding intention, initiation, and duration that persists after adjusting for confounding factors. In some population groups a high proportion of smokers breastfeed successfulIy. Conclusions: The association between maternal smoking and lack of breastfeeding is consistent across different study designs in a range of countries. Given that women who smoke are less likely to intend to breastfeed, however, it cannot be assumed that the relationship between smoking and duration of breastfeeding is a physiological one. If smoking had a consistent negative physiological effect on lactation, one would not expect to see such wide variations in breastfeeding rates among women who smoke. Therefore, it is likely that psychosocial factors are largely responsible for the lower rates of breastfeeding found in women who smoke compared with those who do not.

Austin M-PV; Mitchell PB. Use of psychotropic medications in breastfeeding women: Acute and prophylactic treatment. Australian and New Zealand Journal of Psychiatry 32(6): 778-784, 1998. (40 refs.)

Objectives: The postnatal period is a time of increased onset and relapse of mental illness. It poses a clinical dilemma, as many mothers requiring medication acutely or prophylactically will also choose to breast feed. The present paper first reviews the safety of psychotropes in breast-fed infants and the usefulness of prophylaxis for women at risk of postpartum affective relapse and, second, provides guidelines in the use of psychotropic drugs in breast- feeding women. Methods: A Medline review was conducted reviewing all papers published during the period 1993-1998 (and their associated bibliographies) on the use of psychotropes in breast-feeding women and the prophylactic usefulness of medications in women at risk of affective postpartum relapse. Results: Findings are based on case reports and small, mostly uncontrolled studies. Both tricyclic antidepressants (TCA) and specific serotonin re-uptake inhibitors (SSRIs) appear to be relatively safe in breast feeding. Antidepressants commenced in the early postpartum period may reduce depressive relapse. While prophylactic lithium appears to significantly reduce relapse of affective psychosis in the puerperium, there have been no studies of the anticonvulsants in the puerperium. Finally, high dose antipsychotics should be avoided, as they may be associated with longterm adverse sequelae in the infant. Conclusions: On the basis of current knowledge, the use of SSRIs, TCA, carbamazepine, sodium valproate and short-acting benzodiazepines in breast feeding is relatively safe. If lithium is to be used, close collaboration with a paediatrician is essential. The long-term risks of antipsychotics, especially at high doses, remain to be clarified. Before a decision can be made, the risk-benefit ratio must be clearly outlined and discussed with the mother and her partner.

Backstrand JR; Goodman AH; Allen LH; Pelto GH. Pulque intake during pregnancy and lactation in rural Mexico: Alcohol and child growth from 1 to 57 months. European Journal of Clinical Nutrition 58(12): 1626-1634, 2004. (29 refs.)

Objective: To examine maternal intake of a mildly alcoholic beverage ( pulque) during pregnancy and lactation, and its potential effect on postpartum child growth and attained size. Design: A prospective cohort study that followed mothers ( during pregnancy and lactation) and their offspring ( from birth to approximately 57 months of age). Setting: Six villages in rural, central Mexico. Subjects: Subjects are 58 mother - child pairs. Pulque intake was measured as part of a dietary assessment that was conducted for 2days/month during pregnancy and early lactation. Results: Most mothers consumed pulque during pregnancy (69.0%) and lactation (72.4%). Among pulque drinkers, the average ethanol intake was 125.1 g/week during pregnancy and 113.8 g/week during lactation. Greater pulque intake during lactation, independent of intake during pregnancy, was associated with slower weight and linear growth from 1 to 57 months, and smaller attained size at 57 months. Low-to-moderate pulque intake during pregnancy, in comparison to either nonconsumption or heavy intake, was also associated with greater stature at 57 months. Conclusions: Pulque intake during lactation may have adversely influenced postnatal growth in this population. Public health interventions are urgently needed in Mexico to reduce heavy intake of pulque by pregnant and lactating women, and to replace intake with foods that provide the vitamins and minerals present in the traditional alcoholic beverage.

Bailey B; Ito S. Breast-feeding and maternal drug use. Pediatric Clinics of North America 44(1): 41-48, 1997. (48 refs.)

An increasing number of women are breast-feeding their infants. Concerns may exist if they have to take medications on an acute or chronic basis. This article describes the determinants of drug concentrations in milk and presents ways of evaluating it when no data are available. A list of contraindicated drugs during lactation is presented.

Bailey DN. Cocaine and cocaethylene binding to human milk. American Journal of Clinical Pathology 110(4): 491-494, 1998. (17 refs.)

The binding of cocaine and its ethyl analog, cocaethylene, to human milk was studied using equilibrium dialysis at 4 degrees C. For cocaine, a low-affinity high-capacity binder was noted (equilibrium constant of association, K-a, 3.12 X 10(3) L/mol; concentration of binding sites, B-0, 3.85 x 10(-4) mol/L), as well as a very low affinity, high-capacity binder (K-a, 7.54 x 10(2) L/mol; B-0, 1.42 x 10(-3) mol/L). For cocaethylene, 2 low-affinity, high-capacity binders were suggested: a stronger (K-a, 3.79 x 10(3) L/mol; B-0, 3.27 x 10(-4) mol/L) and a weaker (K-a, 1.84 X 10(3) L/mol; B-0, 8.91 x 10(-4) mol/L) binder The low-affinity, high-capacity binder for cocaine and cocaethylene seems to be albumin, while the weaker nonspecific binding may be due to lipids. Up to 55% of cocaine and up to 61% of cocaethylene were bound to milk; such binding, coupled with the lower pH of milk (6.9) relative to that of serum (7.4), may enhance the mammary secretion of these 2 basic drugs, having important consequences for the nursing infant.

Bartu A; Sharp J; Ludlow J; Doherty DA. Postnatal home visiting for illicit drug-using mothers and their infants: A randomised controlled trial. Australian & New Zealand Journal of Obstetrics & Gynaecology 46(5): 419-426, 2006. (15 refs.)

Background: Postnatal home-visiting programs for illicit drug-using mothers have reported some success in reducing harms in some areas but there is a lack of data on their impact on breastfeeding and immunisation rates. Aims: To investigate the effect on breastfeeding, immunisation and parental drug use. The hypothesis was that the outcomes of the home-visiting group (HVG) would be superior to the control group (CG). Method: One hundred and fifty-two illicit drug-using women were recruited at 35-40 weeks gestation from King Edward Memorial Hospitalital, Perth, Western Australia and randomised after delivery to the HVG or the CG. The HVG had eight home visits; the CG had telephone contact at two months and a home visit at six months. The HVG received education and support for parenting, breastfeeding and child development. This was not provided by the research midwives for the CG. Results: The main drugs were heroin, amphetamines, cannabis and benzodiazepines. Immunisation rates were similar for each group. Median duration of breastfeeding for the HVG was eight weeks (95% CI, 3.8-12.2); for the CG ten weeks (95% CI, 7.3-12.7). Drug use was reduced during pregnancy but increased by six months post-partum in both groups. The retention rates were: HVG 93%; CG 86%. Conclusion: The hypothesis for this study was not supported. Long-term studies are urgently required to assess the effects of parental drug use on infant and child development.

Boshuizen HC; Verkerk PH; Reerink JD; Herngreen WP; Zaadstra BM; Verloove-Vanhorick SP. Maternal smoking during lactation: Relation to growth during the first year of life in a Dutch birth cohort. American Journal of Epidemiology 147(2): 117-126, 1998. (19 refs.)

A recent article by Little et al., (Am J Epidemiology 1994;140:544-54) reported that infants in Seattle, Washington, who were breastfed by mothers who smoked gained more weight than either infants who were breast fed by mothers who did not smoke or infants who were bottle-fed by mothers who smoked. In this study, the authors aimed to verify this result with the use of data from the Social Medical Survey of Children Attending Child Health Clinics (SMOCC) cohort, a nationally representative cohort of 2,151 children born in the Netherlands in 1988-1989. During the first year of life, data on type of milk feeding, weight, length, and head circumference were collected at 1, 2, 3, 6, 9, and 12 months of age. Infants of smokers who were mainly breast fed in the first 3 months of life (n = 117) were compared with similarly breast fed infants of nonsmokers (n = 572), with infants of smokers who had been mainly bottle-fed (n = 270), and with infants of nonsmokers who had been mainly bottle-fed (n = 535. The authors failed to observe any additional increase in body mass, length, or head circumference in infants of breastfeeding smokers compared with infants of the three other groups. When the authors used all of their data to study growth with a multivariate longitudinal regression model (general estimating equations (GEE) model), the data showed clearly reduced growth in breast fed children (limited to the period after the second month of life) and some "catch-up" growth in body mass and head circumference in children with intrauterine exposure to tobacco.

Burt VK; Suri R; Altshuler L; Stowe Z; Hendrick VC; Muntean E. The use of psychotropic medications during breast-feeding. (review). American Journal of Psychiatry 158(7): 1001-1009, 2001. (124 refs.)

Objective: The authors reviewed the risks and benefits regarding the use of psychiatric medications during breast-feeding as they relate to the health and well-being of mothers and their infants. Strategies are discussed to limit infant exposure to a medication while effectively treating the nursing mother. Method: A MEDLINE search of the literature since 1955 was conducted to determine the use of psychotropic medications in breast-feeding women. Search items included each of the categories of psychopharmacologic agents as well as each of the agents in association with nursing, breast-feeding, postpartum, lactation, and breast milk. Results: No controlled studies on the safety of psychotropic medications in nursing mothers were found. Case reports and small case series for each of the different psychotropic medications serve as the basis for suggested treatment guidelines for the management of psychiatric illnesses in breast-feeding women. Thus, each case needs to be considered on an individual basis, with a thoughtful analysis of the risks and benefits of nursing and exposure of the infant to medication. The baseline clinical status of the infant should also be reviewed. Conclusions: Women are vulnerable postpartum to psychiatric disorders and frequently face the need to decide whether to take psychotropic medications while breast-feeding. Should psychiatric medication be indicated, the parents should be provided with the available information regarding the effects of these medications on the neonate. In this way, an informed decision can be made. When psychotropic medication is used during breast-feeding, it is strongly recommended that the infant's pediatrician be involved in monitoring the infant.

Chan CF; Page-Sharp M; Kristensen JH; O'Neil G; Ilett KF. Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk. Journal of Human Lactation 20(3): 322-326, 2004. (16 refs.)

The excretion of naltrexone and its primary metabolite 6,beta-naltrexol in breast milk from a 30-year-old lactating opiate addict undergoing oral naltrexone pharmacotherapy (5 mg/d) was studied. Concentrations of naltrexone and 6,beta-naltrexol in serial milk and plasma samples taken over a 19.3-hour period of a dose interval at steady state were measured by gas chromatography. The calculated infant dose relative to the maternal weight was 0.03% for naltrexone and 0.83% (as naltrexone equivalents) for 6,beta-naltrexol. Total relative infant dose estimated for the complete 24-hour dose interval was 1.06%. Her 6-week-old breastfed infant was healthy, achieving expected milestones, and showed no adverse effects. Only 6,beta-naltrexol was detected in infant plasma and at a very low concentration of 1.1 mug/L. Use of naltrexone during breastfeeding should be undertaken only after an individual risk-benefit analysis.

Chien YC; Liu JF; Huang YJ; Hsu CS; Chao JCJ. Alcohol levels in Chinese lactating mothers after consumption of alcoholic diet during postpartum "doing-the-month" ritual. Alcohol 37(3): 143-150, 2005. (54 refs.)

This study examined the effects of exposure to ethanol through cultural practices by lactating mothers. Specifically, the pharmacokinetics of alcohol in Chinese lactating mothers was investigated after they consumed chicken soup flavored with sesame oil and rice wine (CSSR), a typically prescribed diet during the postpartum "doing-the-month" period. Experimental findings were employed to estimate the potential ethanol dose to neonates and determine associated health risks. Twenty-three lactating mothers were examined. Informed consent was obtained from each subject. The target alcohol dosage was 0.3 g/kg. Milk and blood samples were collected at fixed time intervals from each subject following exposure to CSSR, and alcohol levels were determined. Acute health risks to infants were estimated by comparing the potential infant dosage to an established criterion dose. Blood alcohol level peaked at 20 min after exposure to CSSR and decreased almost linearly thereafter. Alcohol in milk reached a plateau roughly at 20-40 min after exposure to CSSR and then decreased. Alcohol pharmacokinetics among subjects varied widely. The coefficients of variation in subject alcohol concentrations were 16.5-46.2% (mean, 30.0%) for blood and 32.8-57.6% (mean, 44.4%) for milk. Mean maximal alcohol concentration in blood (30.2 +/- 5.0 mg/dl) was achieved at 23.5 +/- 7.6 min and in milk (31.6 +/- 10.3 mg/dl) at 31.7 +/- 12.7 min. Potential infant doses were 3.0-58.8 mg (mean, 13.4 mg), and the predicted time required for milk alcohol level to return to zero level was 175 min. The acute health risks for infants exposed to alcohol through their mothers' milk under the current exposure scenario are low (hazard index < 0.2). Nursing infants at least 3 hr. after ingesting a diet containing alcohol would further reduce potential health risks.

Clarke CA; Purdie DM; Glaser SL. Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors. BMC Cancer 6: article 170, 2006. (33 refs.)

Background: Estrogen/progestin replacement therapy (EPRT), alcohol consumption, physical activity, and breast-feeding duration differ from other factors associated with breast cancer in being immediately modifiable by the individual, thereby representing attractive targets for future breast cancer prevention efforts. To justify such efforts, it is vital to quantify the potential population-level impacts on breast cancer considering population variations in behavior prevalence, risk estimate, and baseline incidence. Methods: For each of these four factors, we calculated population attributable risk percents (PARs) using population-based survey ( 2001) and cancer registry data (1998-2002) for 41 subpopulations of white, non-Hispanic California women aged 40-79 years, and ranges of relative risk (RR) estimates from the literature. Results: Using a single RR estimate, subpopulation PARs ranged from 2.5% to 5.6% for hormone use, from 0.0% to 6.1% for recent consumption of >=2 alcoholic drinks daily, and 4.6% to 11.0% for physical inactivity. Using a range of RR estimates, PARs were 2-11% for EPRT use, 1-20% for alcohol consumption and 2-15% for physical inactivity. Subpopulation data were unavailable for breastfeeding, but PARs using published RR estimates ranged from 2% to 11% for lifetime breastfeeding >=31 months. Thus, of 13,019 breast cancers diagnosed annually in California, as many as 1,432 attributable to EPRT use, 2,604 attributable to alcohol consumption, 1,953 attributable to physical inactivity, and 1,432 attributable to never breastfeeding might be avoidable. Conclusion: The relatively feasible lifestyle changes of discontinuing EPRT use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially.

Clifford TJ; Campbell MK; Speechley KN; Gorodzinsky F. Factors influencing full breastfeeding in a southwestern Ontario community: Assessments at 1 week and at 6 months postpartum. Journal of Human Lactation 22(3): 292-304, 2006. (65 refs.)

Factors associated with full breastfeeding (FBF) at 1 week and at 6 months postpartum were examined in a cohort of 856 mother-infant dyads. Questionnaires were mailed at 4 time points over the first 6 months postpartum. At 1 week, 68% of infants were FBF; at 6 months, 23% were FBF. Factors significantly associated with FBF at 1 week were hospital of delivery, residing with a smoker, maternal shiftwork during pregnancy, and having no prior breastfeeding experience. Cox proportional hazards regression analysis showed that residing with a smoker, having consumed caffeine during pregnancy, reporting elevated maternal trait anxiety at 1 week postpartum, having been employed full-time outside the home prior to delivery, and having received anesthesia/analgesia during labor/delivery were associated with earlier cessation of FBF, whereas not having previous breastfeeding experience predicted its continuation. Although most mothers are breastfeeding early on, a number of factors adversely affect its successful continuation.

Dahlstrom A; Ebersjo C; Lundell B. Nicotine exposure in breastfed infants. Acta Paediatrica 93(6): 810-816, 2004. (30 refs.)

Aim: To study exposure to nicotine in breastfed infants in relation to parental smoking habits. Material and Methods: Forty mother-infant pairs were studied. Twenty non-smoking mothers, 18 smoking (2-20 cigarettes per day) and two snuff-taking mothers were included. All infants were healthy, exclusively breastfed and their postnatal age was 6 wk. During a home visit, parental smoking habits were recorded, and the time of mothers' last smoke or taking of snuff and breastfeeding were recorded. Breast milk and infant urine samples were collected. Concentrations of nicotine and cotinine were analysed with gas chromatography. The amount of milk ingested during the home visit was calculated by weighing the infants. Results: Two non-smoking and non-snuff-taking women had milk containing nicotine (28 and 13 mug/1, respectively). Both had smoking spouses. In the smoking and snuff-taking group, the mean (SD) milk nicotine concentration was 44 (38) mug/1 (n = 36). When milk samples taken 7 h and 0.6 h after smoking were compared, the concentration of milk nicotine increased from 21 to 51 mug/1 (p < 0.01). The two snuff-taking mothers exposed their children to higher milk nicotine concentrations than all but two of the smokers. The concentrations of the metabolite cotinine in infant urine correlated with the dose of nicotine ingested during the home visit (r = 0.84, p < 0.01). Conclusions: Breastfed infants with a smoking or snuff-taking mother are exposed to nicotine in breast milk. The mean intake of nicotine via milk is 7 mug/kg/d. With a shorter time between the mothers' smoking and breastfeeding, the milk nicotine concentration will increase. Both passive smoking at home and snuff-taking were associated with measurable nicotine levels in milk. Healthcare personnel promoting breastfeeding should be aware of these factors influencing exposure to nicotine in the breastfed infant.

Di Napoli A; Di Lallo D; Pezzotti P; Forastiere F; Porta D. Effects of parental smoking and level of education on initiation and duration of breastfeeding. Acta Paediatrica 95(6): 678-685, 2006. (29 refs.)

Aim: To evaluate the effects of parental smoking and level of education on the initiation and duration of breastfeeding in a prospective cohort study on mother - infant pairs. Methods: We studied 543 mother - infant pairs enrolled after delivery at a hospital in Rome. Information about parents' characteristics were obtained from a questionnaire administered in hospital; the outcome of the study was the infant's feeding habits in the preceding 24 h, assessed by telephone every 2 wk. The effects of parental smoking and level of education on initiation and duration of breastfeeding were evaluated through multivariate logistic regression models and time-dependent Cox models. Results: After controlling for confounding factors, we found a negative effect for mothers' smoking both on breastfeeding initiation (odds ratio 2.19, 95% CI 1.05-4.55) and duration (hazard ratio 3.37, 95% CI 1.85-6.13) when at least one parent had a low level of education. Conclusion: Our study shows that maternal smoking, particularly when one of the parents has a low level of education, determines a negative effect on the initiation and duration of breastfeeding. Public health policy should promote educational programmes for both parents focused on quitting smoking, which could have positive effects on the initiation and duration of breastfeeding.

Djulus J; Moretti M; Koren G. Marijuana use and breastfeeding. Canadian Family Physician 51: 349-350, 2005. (10 refs.)

QUESTION One of my breastfeeding patients is using marijuana to combat chronic pain. Is it safe for her to breastfeed? ANSWER Lactating mothers should refrain from consuming cannabinoids. Advising mothers to discontinue breastfeeding if they cannot stop using cannabinoids must incorporate the known risks of formula feeding. Cannabinoid exposure through milk has not been shown to increase neonatal risk, but there are no appropriate studies of this. In every case, nursing babies should be closely monitored.

England L; Brenner R; Bhaskar B; Simons-Morton B; Das A; Revenis M et al. Breastfeeding practices in a cohort of inner-city women: the role of contraindications. BMC Public Health 3: article No. 28, 2003. (35 refs.)

Background: Little is known about the role of breastfeeding contraindications in breastfeeding practices. Our objectives were to 1) identify predictors of breastfeeding initiation and duration among a cohort of predominately low-income, inner-city women, and 2) evaluate the contribution of breastfeeding contraindications to breastfeeding practices. Methods: Mother-infant dyads were systematically selected from 3 District of Columbia hospitals between 1995 and 1996. Breastfeeding contraindications and potential predictors of breastfeeding practices were identified through medical record reviews and interviews conducted after delivery ( baseline). Interviews were conducted at 3 - 7 months postpartum and again at 7 - 12 months postpartum to determine breastfeeding initiation rates and duration. Multivariable logistic regression analysis was used to identify baseline factors associated with initiation of breastfeeding. Cox proportional hazards models were generated to identify baseline factors associated with duration of breastfeeding. Results: Of 393 study participants, 201 ( 51%) initiated breastfeeding. A total of 61 women ( 16%) had at lease one documented contraindication to breastfeeding; 94% of these had a history of HIV infection and/or cocaine use. Of the 332 women with no documented contraindications, 58% initiated breastfeeding, vs. 13% of women with a contraindication. In adjusted analysis, factors most strongly associated with breastfeeding initiation were presence of a contraindication ( adjusted odds ratio [AOR], 0.19; 95% confidence interval [CI], 0.08 - 0.47), and mother foreign-born (AOR, 4.90; 95% CI, 2.38 - 10.10). Twenty-five percent of study participants who did not initiate breastfeeding cited concern about passing dangerous things to their infants through breast milk. Factors associated with discontinuation of breastfeeding ( all protective) included mother foreign-born ( hazard ratio [HR], 0.55; 95% CI 0.39 - 0.77) increasing maternal age ( HR for 5-year increments, 0.80; 95% CI, 0.69 - 0.92), and infant birth weight greater than or equal to 2500 grams ( HR, 0.45; 95% CI, 0.26 - 0.80).Conclusions: Breastfeeding initiation rates and duration were suboptimal in this inner-city population. Many women who did not breastfeed had contraindications and/or were concerned about passing dangerous things to their infants through breast milk. It is important to consider the prevalence of contraindications to breastfeeding when evaluating breastfeeding practices in high-risk communities.

Golding J. Unnatural constituents of breast milk: Medication, lifestyle, pollutants, viruses. Early Human Development 49(Supplement): S29-S43, 1997. (72 refs.)

It is well 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 modem 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 of chemicals 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 heroin and cocaine, and pollutants such as polychlorinated biphenyls and dichlorodiphenyltrichloroethane (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 the 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.

Goodwin DW; Gabrielli WF; Penick EC; Nickel EJ; Chhibber S; Knop J et al. Breast-feeding and alcoholism: The Trotter hypothesis. American Journal of Psychiatry 156(4): 650-652, 1999. (21 refs.)

Objective: The authors' goal was to determine whether early termination of breast-feeding contributes to later alcohol dependence, as proposed more than 200 years ago by the British physician Thomas Trotter. Method: In 1959-1961, a multiple-specialty group of physicians studied 9,182 consecutive deliveries in a Danish hospital, obtaining data about prepartum and postpartum variables. The present study concentrates on perinatal variables obtained from 200 of the original babies who participated in a 30-year high-risk follow-up study of the antecedents of alcoholism. Results: Of the 27 men who were diagnosed as alcohol dependent at age 30, 13 (48%) came from the group weaned from the breast before the age of 3 weeks; only 33 (19%) of the 173 non-alcohol-dependent subjects came from the early weaning group. When challenged by other perinatal variables in a multiple regression analysis, early weaning significantly contributed to the prediction of the severity of alcoholism at age 30. Conclusions: The data support the hypothesis that early weaning may be associated with a greater risk of alcohol dependence later in life.

Gunzerath L; Faden V; Zakhari S; Warren K. National Institute on Alcohol Abuse and Alcoholism Report on Moderate Drinking. (editorial). Alcoholism: Clinical and Experimental Research 28(6): 829-847, 2004. (223 refs.)

In support of the 2005 update of the U.S. Department of Agriculture/U.S. Department of Health and Human Services Dietary Guidelines, the National Institute on Alcohol Abuse and Alcoholism was asked to assess the strength of the evidence related to health risks and potential benefits of moderate alcohol consumption, with particular focus on the areas of cardiovascular disease, breast cancer, obesity, birth defects, breastfeeding, and aging. The findings were reviewed by external researchers with extensive research backgrounds on the consequences and benefits of alcohol consumption. This report now serves as the National Institutes of Health's formal position paper on the health risks and potential benefits of moderate alcohol use.

Haug K; Irgens LM; Baste V; Markestad T; Skjaerven R; Schreuder P. Secular trends in breastfeeding and parental smoking. Acta Paediatrica 87(10): 1023-1027, 1998. (20 refs.)

To explore the association between smoking and breastfeeding, we obtained data from a retrospective questionnaire-based national survey comprising a random sample (n = 34 799) of all mothers giving birth in Norway 1970-91. Variables studied were postpartum smoking habits for both parents, duration of breastfeeding, infant's year of birth and parental age. The response rate was 70% (n = 24 438), During the study period, the maternal postpartum smoking prevalence decreased from 38% to 26%. The proportion breastfeeding at 6 months increased from 15% to 44% among smokers, and from 30% to 72% among nonsmokers. In spite of a considerable increase in breastfeeding both among smokers and non-smokers, the proportion of breastfeeding, non- smoking women at 6 months was twice that of smoking women during the whole period. Furthermore, the duration of breastfeeding was shorter among young mothers and when the fathers were smoking. There was epidemiological evidence that the effect on breastfeeding of smoking might represent both biological and social mechanisms.

Heil SH; Subramanian MG. Alcohol and the hormonal control of lactation. Alcohol Health and Research World 22(3): 178-184, 1998. (34 refs.)

All mammals produce milk to nourish their young. Milk production (i.e., lactation), which occurs in the mammary glands, is regulated by several hormones, most prominently prolactin and oxytocin. Studies in both humans and laboratory animals have demonstrated that maternal alcohol consumption before and during lactation can interfere with the functions of both of those hormones. Moreover, animal studies found that maternal alcohol consumption during pregnancy and even earlier in the mother's life can impair mammary gland development. Maternal alcohol consumption and result in suckling deficits of the offspring. Alcohol (and possibly its breakdown products) can pass from the maternal circulation into the breast milk. The effects of these substances on the infant, however, are still unknown.

Public Domain

Hemminki K; Chen B. Parental lung cancer as predictor of cancer risks in offspring: Clues about multiple routes of harmful influence? International Journal of Cancer 118(3): 744-748, 2006. (31 refs.)

The carcinogenic effects of active smoking have been demonstrated for many sites, but the effects of passive smoking and exposures during pregnancy and breastfeeding are. less well documented. We examined whether 0-70-year-old offspring of parents with lung cancer are at a risk of cancer that cannot be explained by their smoking or familial risk. It was assumed that known target sites for tobacco carcinogenesis would be affected, if any. The nationwide Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used to calculate age-specific standardized incidence ratios (SIRs). Among offspring of affected mothers, increased risks were observed for upper aerodigestive (SIR 1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer (6.41) in one age group. The risk of bladder cancer was found in younger age groups than that of lung cancer. Cancers at many of these sites, but not the kidney or the bladder, were in excess in offspring of affected fathers. Nasal cancer was even increased when either parent was diagnosed with lung cancer; the highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure.

Ho E; Collantes A; Kapur BM; Moretti M; Koren G. Alcohol and breast feeding: Calculation of time to zero level in milk. Biology of the Neonate 80(3): 219-222, 2001. (28 refs.)

Objective: To create a nomogram that will guide lactating women who drink socially on how to avoid neonatal exposure to ethanol through breast milk. Design: Pharmacokinetic modeling of ethanol elimination from milk based on reference values. Calculation of the time to zero alcohol in breast milk for a range of doses and body weights. Results: The elimination of alcohol and time-to-zero levels in breast milk are described in a nomogram as a function of the amount of alcohol consumed and the body weight of the woman. Conclusions: Careful planning of a breast feeding schedule, by storing milk before drinking and/or waiting for complete alcohol elimination from the breast milk, can ensure women that their babies are not exposed to any alcohol.

Horta BL; Kramer MS; Platt RW. Maternal smoking and the risk of early weaning: A meta-analysis. American Journal of Public Health 91(304-307), 2001. (48 refs.)

Objectives. This study reviewed evidence on the effect of maternal smoking on early weaning. Methods. The following databases and journals were searched: Medline, Scientific Citation Index, Pediatrics, Journal of Pediatrics, New England Journal ofMedicine, and Lancet. Analysis was restricted to studies in which infants who had never been breastfed were excluded or the prevalence of breastfeeding initiation was more than 90%. Results. In smoking vs nonsmoking mothers, the random effects odds ratio for weaning before 3 months was 1.93 (95% confidence interval [CI]= 1.55, 2.40). An adjusted odds ratio of 1.50 (95% CI=1.34, 1.68) was shown in studies that had lost-to-follow-up rates below 15% and included adequate adjustment for confounding. Conclusions. Maternal smoking increases the risk of early weaning.

Howard CR; Lawrence RA. Breast-feeding and drug exposure. Obstetrics and Gynecology Clinics of North America 25(1): 195-X, 1998. (89 refs.)

Breast-feeding provides many health benefits for mothers and infants. Concerns about the safety of breast-feeding, however, arise when the physician is confronted with a woman who wishes to breast-feed her infant, but who has an illicit drug use problem or history. More common, but perhaps more confusing, is the management of a mother who uses "relatively contraindicated" substances such as tobacco or alcohol during breast-feeding. How should the physician counsel such mothers? How should mother-infant dyads be followed? What are the benefits and risks of continuing to breast-feed? This article provides guidance for the obstetrician confronted with these clinical dilemmas.

Howard CR; Lawrence RA. Drugs and breastfeeding. (review). Clinics in Perinatology 26(2): 447-478, 1999. (128 refs.)

Maternal medications pose a common concern for pediatricians in caring for the breastfed infant. Although current literature supports the safety or the vast majority of medications during breastfeeding, at times medications may make it necessary to temporarily interrupt or discontinue breastfeeding. Also of concern are the use of herbal remedies and caffeine as well as 'relatively contraindicated' substances like nicotine and alcohol during breastfeeding. A. framework for assessing the safety of maternal drug usage during breastfeeding and for minimizing any associated risks to the nursing infant is presented.

Iqbal MM; Sobhan T; Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatric Services 53(1): 39-49, 2002

Objective: Despite the widespread use of benzodiazepines during pregnancy and lactation, little information is available about their effect on the developing fetus and on nursing infants. The authors review what is currently known about the effects of benzodiazepine therapy on the fetus and on nursing infants. Methods. A MEDLINE search of the literature between 1966 and 2000 was conducted with the terms "benzodiazepines," "diazepam," "chlordiazepoxide," "clonazepam," "lorazepam", "alprazolam", pregnancy," "lactation," "fetus," and "neonates." Results. Currently available information is insufficient to determine whether the potential benefits of benzodiazepines to the mother outweigh the risks to the fetus. The therapeutic value of a given drug must be weighed against theoretical adverse effects on the fetus before and after birth. The available literature suggests that it is safe to take diazepam during pregnancy but not during lactation because it can cause lethargy, sedation, and weight loss in infants. The use of chlordiazepoxide during pregnancy and lactation seems to be safe. Avoidance of alprazolam during pregnancy and lactation would be prudent. To avoid the potential risk of congenital defects, physicians should use the benzodiazepines that have long safety records and should prescribe a benzodiazepine as monotherapy at the lowest effective dosage for the shortest possible duration. High peak concentrations should be avoided by dividing the daily dosage into two or three doses. Conclusions: Minimizing the risks of benzodiazepine therapy among pregnant or lactating women involves using drugs that have established safety records at the lowest dosage for the shortest possible duration, avoiding use during the first trimester, and avoiding multidrug regimens.

Jansson LM; Velez M; Harrow C. Methadone maintenance and lactation: A review of the literature and current management guidelines. (review). Journal of Human Lactation 20(1): 62-71, 2004. (60 refs.)

Methadone offers significant therapeutic benefits to the population of pregnant, opiate-dependent women and is currently the treatment of choice for this group. Yet the problem of women who elect to breastfeed while on methadone maintenance frequently vexes providers. Although breast milk offers advantages clearly beneficial to the general population of infants, there is debate about recommending breastfeeding to postpartum women receiving methadone maintenance. Although previous research has shown that amounts of methadone in breast milk appear to be very small, and therefore breastfeeding seems to be safe, women on methadone do not often breastfeed, for a variety of reasons. This article provides an overview of the issues facing providers in treating methadone-maintained women who elect to breastfeed. A comprehensive review of existing literature on the subject is offered, along with clinical advice for practitioners providing care to this population of women and children.

Koren G. Drinking alcohol while breastfeeding: Will it harm my baby? Canadian Family Physician 48: 39-41, 2002. (12 refs.)

QUESTION I recently delivered a healthy, full-term baby and am now breastfeeding exclusively. I abstained from drinking alcohol during my entire pregnancy and am wondering if drinking alcohol now would harm my nursing baby. ANSWER Nursing mothers who choose to drink alcohol during the postpartum period should carefully plan a breastfeeding schedule by storing milk before drinking and waiting for complete elimination of alcohol from their breast milk after drinking. Motherisk has created an algorithm to estimate how long it takes to eliminate alcohol from breast milk.

LaGasse LL; Messinger D; Lester BM; Seifer R; Tronick EZ; Bauer CR et al. Prenatal drug exposure and maternal and infant feeding behaviour. Archives of Disease in Childhood 88(5, Special Issue): F391-F399, 2003. (47 refs.)

Objective: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates. Methods: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction. Results: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions ( 638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts ( 29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems. Conclusions: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.

Larimore WL; Petrie KA. Drug use during pregnancy and lactation. Primary Care 27(1): 35-53, 2000. (27 refs.)

This article reviews the basic principles of pharmacology and teratogenicity of drugs for the pregnant and lactating woman and summarizes the Food and Drug Administration, American College of Obstetrics and Gynecology, and American Academy of Pediatrics classifications. These categories were devised for caregivers of both women and their babies. The authors propose a two/three letter category system to assist those who, like family physicians, must care for women while pregnant and while lactating. Common problems from everyday practice are reviewed, with an emphasis on the important drugs to use and avoid in a wide variety of everyday clinical settings to help the busy primary care physician in making decisions about medications in pregnancy and lactation

Little RE; Northstone K; Golding J. Alcohol, breastfeeding, and development at 18 months. Pediatrics 109(5): NIL_9-NIL_14, 2002. (14 refs.)

Objective. We aimed to replicate a previous study of 1-year-olds that reported a deficit in motor development associated with moderate alcohol use during lactation, using a different but comparable population. Methodology. The mental development of 915 18-month-old toddlers from a random sample of a longitudinal population-based study in the United Kingdom was measured using the Griffiths Developmental Scales. Frequent self-administered questionnaires during and after pregnancy provided maternal data. The dose of alcohol available to the lactating infant was obtained by multiplying the alcohol intake of the mother by the proportion of breast milk in the infant's diet. We compared this dose with the Griffiths Scales of Mental Development, taking into account potentially confounding variables. Result. Three of the Griffiths scales increased slightly but significantly with increasing infant alcohol exposure; there was no association in the remaining 2 or average of the scales. Discussion. We were unable to replicate the earlier deficit in motor skills associated with lactation alcohol use. One reason may be that the dose of alcohol reaching the lactating infant is small, and tests of infants and toddlers have limited ability to pick up small effects. Studies of older children may resolve the question of the safety of drinking while nursing.

Longhurst JG; Weiss E. Use of psychotropic medications during lactation. (letter). American Journal of Psychiatry 155(11): 1643-1643, 1998. (6 refs.)

Ludvigsson JF; Ludvigsson J. Socio-economic determinants, maternal smoking and coffee consumption, and exclusive breastfeeding in 10205 children. Acta Paediatrica 94(9): 1310-1319, 2005. (40 refs.)

Aim: To examine socio-economic factors, smoking, coffee consumption and exclusive breastfeeding duration. Methods: This study was part of a prospective cohort study of children born between 1 October 1997 and 1 October 1999 (the All Babies in Southeast Sweden (ABIS) Study). Eleven socio-economic characteristics (parental employment, civil status, whether parents were born in Sweden, parental education, residence at birth and during child's first year, crowded living), maternal smoking, coffee consumption, infant sex, siblings, parental age, and maternal alcohol consumption during pregnancy were analysed using logistic regression and Cox's proportional hazards method. All data were obtained through questionnaires distributed at infant birth and at 1 y of age. Exclusive breastfeeding duration <4 mo and actual breastfeeding duration were our main outcome measures. Results: Out of 10205 infants, 2206 (21.6%) were exclusively breastfed for less than 4 mo ("short exclusive breastfeeding"; SEBF). Backward stepwise regression analysis identified the following risk factors for SEBF: maternal smoking (95% confidence interval for adjusted odds ratio, 95% CI AOR 2.00-2.82), low maternal education (95% CI AOR 1.45-2.19), maternal employment less than 3 mo during pregnancy (95% CI AOR 1.17-1.54), paternal age <= 29 y (95% CI AOR 1.14-1.47), maternal age <= 29 y (95% CI AOR 1.08-1.39) and low paternal education (95% CI AOR 1.08-1.48). The odds ratio for SEBF increased with the number of cigarettes smoked. Coffee consumption was not associated with duration of exclusive breastfeeding. Conclusion: This study indicates that socio-economic factors and smoking may be of importance to the risk of breastfeeding exclusively for less than 4 mo, while coffee consumption is not.

Maitra R; Menkes DB. Psychotropic drugs and lactation. (letter). New Zealand Medical Journal 109(1024): 217-219, 1996. (3 refs.)

Malone K; Papagni K; Ramini S; Keltner NL. Biological perspectives: Antidepressants, antipsychotics, benzodiazepines, and the breastfeeding dyad. (editorial). Perspectives in Psychiatric Care 40(2): 73-85, 2004. (52 refs.)

Mennella JA. Infants' suckling responses to the flavor of alcohol in mother's milk. Alcoholism: Clinical and Experimental Research 21(4): 581-585, 1997. (45 refs.)

Previous research has demonstrated that alcohol consumption by lactating women diminished milk intake by their infants during breast feeding. To determine whether this was due to the infants' responding to the altered flavor of the milk, the author evaluated the infants' intake and sucking responses to alcohol-flavored human milk outside the context of breast feeding, thereby separating the changes due to the infants' response to the flavor from any other changes that could also result from acute maternal alcohol consumption such as alterations in milk ejection or the composition of milk. The testing procedure consisted of a two-bottle preference test that was composed of four 60-second trials in which the mother's milk flavored with alcohol was alternated with the mother's milk alone in an ABBA or BAAB design. Attached to the nipple of each bottle was a transducer that responded to pressure changes produced by the infant's sucking. The infants consumed significantly more and sucked more frequently when drinking the alcohol-flavored milk, compared with the unaltered milk. That experience with the flavor of alcohol in mothers' milk modified the infants' responses to alcohol flavor is suggested by the relationship between the reported frequency of mothers' drinking during lactation and the infant's rhythm and frequency of sucking when feeding the alcohol-flavored milk. These findings indicate that infants can readily detect the flavor of alcohol in mother's milk but that the decrease in consumption at the breast after maternal alcohol consumption is apparently not due to the infants rejecting the flavor of alcohol in their mothers' milk.

Mennella JA. Regulation of milk intake after exposure to alcohol in mothers' milk. Alcoholism: Clinical and Experimental Research 25(4): 590-593, 2001. (27 refs.)

Objective: Contrary to the folklore which claims that drinking alcohol during lactation benefits both mother and infant, previous research in our laboratory revealed that breastfed infants consumed significantly less milk during the immediate hours after their mothers' consumption of an alcoholic beverage. Because breastfed infants are clearly capable of regulating milk intake, the present study tested the hypothesis that infants would compensate for the diminished milk intake if their mothers then refrained from drinking alcohol. Methods: A within-subjects design that controlled for time of day was implemented because of the great individual and daily variation in both milk composition and intake. To this end, 12 exclusively breastfed infants and their mothers were tested on 2 days separated by I week. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other, the order was counterbalanced. The infants' behaviors were monitored for the next 16 hr, the first 4 hr of monitoring on each test day occurred at the Monell Center. The infants fed an demand and immediately before and after each feeding, infants were weighed without a change in clothing. Results: Consistent with previous findings, infants consumed significantly less milk during the 4 hr immediately after exposure to alcohol in mothers' milk compared with the control condition. Compensatory increases in intake were then observed during the 8 to 16 hr after exposure when mothers refrained from drinking alcohol. Conclusions: These findings demonstrate that short-term exposure to small amounts of alcohol in mothers' milk produces distinctive changes in the infants' patterns of feeding.

Mennella JA; Gerrish CJ. Effects of exposure of alcohol in mother's milk on infant sleep. Pediatrics 101(5): E21-E25, 1998. (42 refs.)

Objective. To test the hypothesis that exposure to alcohol in breast milk affects infants' sleep and activity levels in the short term. Methods. Thirteen lactating women and their infants were tested on 2 days, separated by an interval of 1 week. On each testing day, the mother expressed 100 ml of milk, while a small, computerized movement detector called an actigraph was placed on the infant's left leg to monitor sleep and activity patterning. After the actigraph had been in place for similar to 15 minutes, the infants ingested their mothers breast milk flavored with alcohol (32 mg) on one testing day and breast milk alone on the other. The infants' behaviors were monitored for the next 3.5 hours. Results. The infants spent significantly less time sleeping during the 3.5 hours after consuming the alcohol-flavored milk (78.2 minutes compared with 56.8 minutes after feeding alcohol in breast milk). This reduction was apparently attributable to a shortening in the longest sleeping bout (34.5 compared with 56.7 minutes for sleeping after breast milk alone) and the amount of time spent in active sleep (25.8 minutes compared with 44.2 minutes after breast milk alone); the decrease in active sleep was observed in all but 2 of the 13 infants tested. Conclusions. Although the mechanisms underlying the reduction in sleep remain to be elucidated, this study shows that short-term exposure to small amounts of alcohol in breast milk produces distinctive changes in the infant's sleep-wake patterning.

Narayanan U; Birru S; Vaglenova J; Breese CR. Nicotinic receptor expression following nicotine exposure via maternal milk. Neuroreport 13(7): 961-963, 2002. (18 refs.)

Studies have shown nicotine is excreted into maternal milk, so that suckling offspring would be a target of the drug during the pre- weaning period. Since nicotine exposure leads to an upregulation of neuronal nicotinic receptors, this study examines the hypothesis that nicotine delivered via maternal milk is capable of altering neuronal nicotinic receptor regulation in the drug-exposed rat pups. The present study showed that postnatal nicotine exposure via maternal milk was sufficient to induce an upregulation in brain nicotinic receptors similar to that seen in adults that smoke. Such exposure may result in altered neuronal development and synaptic activity and structure, potentially leading to long-term behavioral, learning, and memory deficits.

Niebyl JR. Drug use in pregnancy and lactation. IN: Pearlman MD; Tintinalli JE, eds. Emergency Care of the Woman. New York: McGraw Hill Book Co., 1997. pp. 165-179. (119 refs.)

This chapter addresses drug use within pregnancy and during breast feeding. It begins with an introduction of the general principles in terms of drug transfer from mother to fetus, drug teratogenesis, and the FDA's drug labeling for use during pregnancy. When drugs are prescribed during pregnancy, the indications should be clear and the risk/benefit ratio justify use, and if possible therapy postponed until after the first trimester. Most drug therapy is compatible with lactation, because the amount excreted into breast milk is so small that it is pharmacologically insignificant. The author reviews the teratogenic effects of specific drugs, organized by 11 drug groups, followed up a discussion of drug use during lactation. The focus is upon therapeutic agents commonly used in emergency setting with known adverse effects during pregnancy, drusg contraindicated during breast feeding, drugs with unknown effects on nursing, drugs potentially affecting milk supply, and drugs considered compatible with breast-feeding. This chapter is limited to prescription drugs.

Ozkan B; Ermis B; Tastekin A; Doneray H; Yildirim A; Ors R. Effect of smoking on neonatal and maternal serum and breast milk leptin levels. Endocrine Research 31(3): 177-183, 2005. (25 refs.)

Maternal smoking is considered to be a risk factor for low birth weight. It is hypothesized that alteration in leptin concentration may be associated with reduced fetal growth. In this study, we assess the effect of smoking during pregnancy on maternal and neonatal serum leptin concentrations, and also on breast milk leptin levels. When the infants were brought to routine physical examination at 7 days old, blood samples and breast milk specimens were taken for leptin measurement from mothers who smoked during pregnancy and their newborns. Nonsmoking mothers and their infants were recruited randomly over the same period as a control group. Maternal age, number of pregnancy, weight of the mothers, birth weight, and gestational age of the infants were similar in both groups ( p > 0.05). There was no significant difference between groups in maternal serum and breast milk leptin levels ( p = 0.14 and p = 0.96, respectively). However, serum leptin levels were found significantly lower in neonates born to smoking mothers compared with infants born to nonsmoking mothers ( p = 0.02). Our findings suggest that maternal smoking dose not have an effect on maternal serum and breast milk leptin levels but decreases neonatal serum leptin concentration independent of birth weight.

Page-Sharp M; Hale TW; Hackett LP; Kristensen JH; Ilett KF. Measurement of nicotine and cotinine in human milk by high-performance liquid chromatography with ultraviolet absorbance detection. Journal of Chromatography B 796(1): 173-180, 2003. (31 refs.)

A high-performance liquid chromatographic (HPLC) assay for the determination of nicotine and cotinine in human milk was developed using an extraction by liquid-liquid partition combined with back extraction into acid, and followed by reverse-phase chromatography with UV detection of analytes. The assay was linear up to 500 mug/l for both nicotine and cotinine. Intra- and inter-day relative standard deviations (R.S.D.) were <10% (25-500 mug/l) for both nicotine and cotinine. Limits of quantitation (LOQ) were 10 and 12 mug/l for nicotine and cotinine, respectively, while the limits of detection (LOD) were 8 and 10 mug/l for nicotine and cotinine, respectively. The mean recoveries were 79-93% (range 25-500 mug/l) for nicotine and 78-89% (range 25-500 mug/l) for cotinine. The amount of fat in the milk did not affect the recovery. We found that this method was sensitive and reliable in measuring nicotine and cotinine concentrations in milk from a nursing mother who participated in a trial of the nicotine patch for smoking cessation.

Pepino MY; Abate P; Spear NE; Molina JC. Heightened ethanol intake in infant and adolescent rats after nursing experiences with an ethanol-intoxicated dam. Alcoholism: Clinical and Experimental Research 28(6): 895-905, 2004. (77 refs.)

Background: Preweanling rats detect ethanol (175 mg/100 ml) in maternal milk when the dam is moderately intoxicated. Repeated experiences with the intoxicated dam facilitate subsequent recognition of ethanol's chemosensory attributes and promote ethanol-related memories with a negative hedonic content. This memory has been attributed to the infant's acquired association between ethanol's chemosensory attributes and its disruptive effects on maternal care. In this study, infant and adolescent ethanol intake patterns were analyzed as a function of prior interactions, during early infancy, with their intoxicated dams. Methods: During postpartum days 3, 5, 7, 9, 11, and 13, breast-feeding dams received an intragastric administration of either 2.5 g/kg of ethanol or water. Pups whose dams had been given one of these two maternal treatments were tested on postnatal day 15 for ingestion of 0% (water), 2.5, 5.0, or 10% v/v ethanol solution. During adolescence, remaining animals from these litters were first adapted to ingest water from drinking tubes and then were given simultaneous access to tap water and a given ethanol solution. The first day, a 3% v/v ethanol solution was used. This solution was increased by 1% ethanol each following day until the solution was 6% v/v ethanol. Results: Maternal drug treatment did not affect the body weights of dams, infants, or adolescents. Water intake during infancy and adolescence also was unaffected by prior maternal treatment. However, infants that had previously interacted with ethanol-intoxicated dams exhibited heightened ethanol intake scores (grams per kilogram and percentage body weight gains), especially when tested with 5 or 10% v/v ethanol solutions. Similarly, adolescent males (but not females) that had interacted with an intoxicated dam during infancy also had higher ethanol consumption levels than those that had interacted with a nonintoxicated dam. Conclusions: Contrary to what might be expected in animals that acquire an aversive memory for ethanol's chemosensory cues as a function of prior interactions with an intoxicated mother, these results indicate that such interactions promote a long-lasting increase in ethanol intake. These results suggest that rats reared by intoxicated dams become sensitive to the negative reinforcing properties of ethanol.

Powers NG. Slow weight gain and low milk supply in the breastfeeding dyad. Clinics in Perinatology 26(2): 399-VII, 1999. (77 refs.)

Maternal perception of insufficient milk is a widespread phenomenon in modem breastfeeding. This article addresses underlying physiology, feeding patterns, growth patterns, and medical complications as they impact milk supply and infant growth. The complexity of mother-infant factors leads to a broad differential diagnosis. Problem-oriented management is discussed with the goal of preventing low milk supply, intervening promptly for feeding problems, promoting infant growth, and preserving the breastfeeding relationship.

Sarkar M; Djulus J; Koren G. When a cocaine-using mother wishes to breastfeed: Proposed guidelines. (editorial). Therapeutic Drug Monitoring 27(1): 1-2, 2005. (9 refs.)

Schuetze P; Das Eiden R; Chan AWK. Effects of alcohol in breast milk on infant behavioral state and mother-infant feeding interactions. Infancy 3(3): 249-363, 2002. (44 d refs.)

The effects of alcohol in breast milk on infant behavioral state and mother-infant feeding interactions were studied. The research sample included 14 mother-infant dyads that were tested on two occasions that consisted of an alcohol and a nonalcohol condition. Mother-infant interactions during feeding were videotaped and coded for dyadic reciprocity, maternal noncontingency, and dyadic conflict. The infants were then observed for 1 hour after receiving plain breast milk or breast milk containing alcohol. Recordings of behavioral state, startles, and tremors were recorded every 30 seconds. The following results of the study were seen: (1) higher noncontingency and dyadic conflict in mother-infant interactions in the alcohol condition; and (2) following consumption of alcohol-containing breast milk, more frequent changes in infant behavior state, with more frequent startle, less time in quiet sleep, and more time in quiet alert and crying states. The authors suggest that exposure to breast milk containing alcohol may not have a sedating effect, as commonly believed.

Sorensen HJ; Mortensen EL; Reinisch JM; Mednick SA. Early weaning and hospitalization with alcohol-related diagnoses in adult life. American Journal of Psychiatry 163(4): 704-709, 2006. (28 refs.)

Objective: This study attempted to determine whether lack of breast-feeding or a short duration of breast-feeding during infancy is associated with an elevated risk of hospitalization with alcohol-related diagnoses in adult life. Method: The study was a prospective longitudinal birth cohort design conducted in a sample of 6,562 men and women, all of whom were born in Copenhagen, Denmark, between October 1959 and December 1961. The sample was divided into two categories based on duration of breast-feeding, as assessed by a physician interview with mothers at a 1-year examination. Psychiatric hospitalizations with alcohol-related diagnoses according to ICD-8 or ICD-10 were identified in the Danish Psychiatric Central Register in 1999. Nine potential confounders were included as covariates: gender of the cohort member, maternal age, parental social status, maternal prenatal smoking, unwanted pregnancy, maternal and paternal psychiatric hospitalization with alcohol-related diagnosis, and maternal and paternal psychiatric hospitalization with other diagnosis. Results: Alcohol-related diagnoses were more frequent in men, but the results were comparable for men and women. The adjusted predictive effect of early weaning was 1.47. Elevated relative risks were also associated with maternal smoking during pregnancy ( 1.52) and unwanted pregnancy status ( 1.59). Other independent predictors were male gender, maternal psychiatric hospitalization with alcohol-related diagnosis, and low parental social status. Conclusions: Independent of a number of other risk factors for alcoholism, a significant association between early weaning and elevated risk of hospitalization with alcohol-related diagnoses was observed.

Spigset O; Hagg S. Excretion of psychotropic drugs into breast milk: Pharmacokinetic overview and therapeutic implications. (review). CNS Drugs 9(2): 111-134, 1998. (151 refs.)

The prescription of psychotropic drugs during lactation is a clinically important but complex issue. Most of the information available on the excretion of these drugs into breast milk and the impact that this has on the breast-fed infant is based on single care reports. For many drugs, data are extremely sparse or even lacking. Although all psychotropic drugs that have been studied are excreted into breast milk, there is limited knowledge on the practical impact of the, often very low, concentrations found. On the other hand, the capacity for drug elimination is often impaired in infants compared with adults, indicating that even exposure to apparently insignificant doses through breast milk may cause adverse effects, particularly in premature neonates or after long term exposure. In addition, large methodological problems exist in the assessment of possible adverse drug reactions in neonates and infants. Nevertheless, based on current knowledge, some recommendations can be suggested. In mothers receiving tricyclic antidepressants, it seems unwarranted to recommend that breast feeding should be discontinued. The exception to this rule is in mothers receiving doxepin. The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) fluoxetine should probably be avoided during lactation. Treatment with other SSRIs (citalopram, fluvoxamine, paroxetine or sertraline) seems to be compatible with breast feeding, although this view should be considered as preliminary due to the lack of data. Regarding anxiolytic benzodiazepines, adverse drug reactions id infants have been described during maternal treatment with diazepam. Therefore, oxazepam seems to be preferable to diazepam in lactating women. Nevertheless, during maternal treatment with all anxiolytic benzodiazepines, infants should be observed for signs of sedation and poor suckling, and if high doses have to be used and long term administration is required, breast feeding should probably be discontinued. Hypnosedative benzodiazepines with short elimination half-lives, such as midazolam, are preferable to drugs with long half-lives, such as nitrazepam and quazepam. However, zopiclone and zolpidem are probably more appropriate than the benzodiazepines when a hypnotic drug is required. Although animal studies have indicated that alterations in central dopaminergic systems may occur after exposure to antipsychotics through breast milk, it is not known whether these results are relevant to the situation in suckling infants. The very limited clinical data available indicate that high potency antipsychotics can be used cautiously during lactation when low doses are given. If treatment with chlorpromazine, clozapine or sulpiride is considered necessary, breast feeding should probably be discontinued. Breast feeding should be stopped when the mother is receiving lithium. However, maternal treatment with carbamazepine or valproic acid (sodium valproate) appears to be compatible with breast feeding. In general, if a psychotropic drug is considered necessary in a lactating mother, a drug that is minimally excreted into breast milk or that has been found in negligible amounts in the plasma of a breast-fed infant, and has not been associated with detrimental effects in infants, is preferable. Due to the considerable pharmacokinetic variability of most psychotropic drugs, therapeutic drug monitoring should be used to ensure that the mother is not treated with higher doses than are necessary. The dose received by the infant can be further reduced if breast feeding is avoided at times of peak drug concentration in the milk. As breast milk has considerable nutritional, immunological and other advantages over formula milk, the possible risks to the infant should always be carefully weighed, on an individual basis, against the benefits of continuing breast feeding.

Stepans MBF; Wilhelm SL; Dolence K. Smoking hygiene: Reducing infant exposure to tobacco. Biological Research for Nursing 8(2): 104-114, 2006. (53 refs.)

The American Academy of Pediatrics recently removed nicotine from the list of drugs contraindicated during breastfeeding. The objective of this study was to evaluate the feasibility of determining the effect of a smoking hygiene intervention on infants of breastfeeding mothers who smoke cigarettes. An experimental design with repeated measures was used. A convenience sample of 35 mother-infant dyads from seven sites was recruited and randomly assigned to the intervention or control group. Of the 27 dyads completing the study, 16 were in the experimental group and 11 were in the control group. Smoking hygiene was introduced when infants were 2 weeks old and reinforced when they were 3 and 5 weeks old. At these three data points, infant health and urinary nicotine and cotinine levels were measured, as well as the mothers' breast-milk nicotine and cotinine levels and smoking hygiene behaviors. Recruiting and retaining a sample of breastfeeding mothers who smoke proved difficult. Only 27% of women in the intervention group implemented all aspects of the smoking hygiene intervention behaviors. Repeated-measures ANOVA revealed no difference in a) infant urinary nicotine and cotinine levels or b) breast-milk nicotine and cotinine levels between the two groups. The McNemar test for related samples revealed no difference between frequency of respiratory symptoms in either the control or intervention groups when Week 2 levels were compared with levels at Weeks 3 and 5. Mothers were not successful in adhering to the smoking hygiene intervention. To adequately test interventions, strategies must be developed to help women incorporate health-promoting behaviors into their lives.

Wallace C; Burns L; Gilmour S; Hutchinson D. Substance use, psychological distress and violence among pregnant and breastfeeding Australian women. Australian and New Zealand Journal of Public Health 31(1): 51-56, 2007. (23 refs.)

Objective: To identify the population prevalence and demographic characteristics of pregnant and/or breastfeeding Australian women who use licit and illicit substances and their experience of psychological distress and violence. Methods: Data from the 2004 National Drug Strategy Household Survey were used to determine the prevalence of substance use, psychological distress and violence experienced by pregnant and/or breastfeeding women. Results: A total of 976 pregnant and/or breastfeeding women were included. These women were significantly less likely than non-pregnant women to consume alcohol (47% vs. 85%) or any illicit drug (6% vs. 17%); however, there was no significant difference in tobacco smoking (20% vs. 25%). Self-reported psychological distress was significantly more frequent in the non-pregnant group (42%) than in the pregnant group, irrespective of substance use status. At a population level, pregnant and/or breastfeeding women were not at a heightened risk of psychological distress or violence. Discussion: These findings highlight the importance of targeting older, tertiary-educated and relatively affluent mothers and those living in regional areas for drug and alcohol education campaigns and treatment. Implications: Simplifying the National Health and Medical Research Council pregnancy-specific alcohol guidelines, improving clinician training, and increasing the availability of treatment options in rural and regional areas may assist in the identification, referral and provision of assistance to substance using pregnant/breastfeeding women.

Wilbourne P; Wallerstedt C; Dorato V; Curet LB. Clinical management of methadone dependence during pregnancy. (review). Journal of Perinatal and Neonatal Nursing 14(4): 26-45, 2001. (107 refs.)

This is a review of the literature regarding the clinical management of pregnant women maintained on methadone treatment. The prevalence of opiate use, definition of opiate dependence, common concerns regarding methadone use in pregnancy, and maternal/fetal harm are addressed. Recommendations for nurses are synthesized from the clinical literature, clinical experiences, and the empirical literature. These recommendations address: antepartum issues including treatment, dosage and pharmacological considerations, medical conditions and lab tests, intrapartum issues, postpartum concerns including breastfeeding, neonatal withdrawal, and developmental effects associated with methadone.

Winecker RE; Goldberger BA; Tebbett IR; Behnke M; Eyler FD; Karlix JL et al. Detection of cocaine and its metabolites in breast milk. Journal of Forensic Sciences 46(5): 1221-1223, 2001. (13 refs.)

A method was developed for measuring cocaine and its metabolites, benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester, cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas chromatography/mass spectrometry. Limits of detection for this method ranged from 2.5 to 10 ng/mL, and limits of quantitation ranged from 5 to 50 ng/mL. For each of the compounds measured by this method, linear response was demonstrated to 750 ng/mL. Breast milk was collected from 11 mothers who admitted to drug use during pregnancy and ten drug-free volunteers serving as control subjects. Cocaine was detected in six of the specimens obtained from drug- exposed subjects, and in none of the drug-free control subjects. In breast milk specimens where cocaine and one or more of its metabolites were detected, the concentration of parent compound was greater than any of the metabolites. The highest cocaine concentration found was over 12 mug/mL. Breast-fed infants of cocaine abusing mothers may be exposed to significant amounts of drug orally.

Wojnar-Horton RE; Kristensen JH; Yapp P; Ilett KF; Dusci LJ; Hackett LP. Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme. British Journal of Clinical Pharmacology 44(6): 543-547, 1997. (22 refs.)

Aims. Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug. Methods. Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20-80 mg (0.3-1.14 mg kg(-1)). Blood was also obtained from eight of their infants. Methadone concentration in these samples was quantified by h.p.l.c. The infants were observed for withdrawal symptoms. Results. The mean (95% CI) milk/plasma ratio was 0.44 (0.24-0.64). Exposure of the infants, calculated assuming an average milk intake of 0.15 l kg(-1) day and a bioavailability of 100% was 17.4 (10.8-24) mu g kg(-1) day(-1). The mean infant dose expressed as a percentage of the maternal dose was 2.79 (2.07-3.51)%. Methadone concentrations in seven infants were below the limit of detection for the h.p.l.c. assay procedure, while one infant had a plasma methadone concentration 6.5 mu g l(-1). Infant exposure to methadone via human milk was insufficient to prevent the development of a neonatal abstinence syndrome which was seen in seven (64%) infants. No adverse effects attributable to methadone in milk were seen. Conclusions. We conclude that exposure of breast fed infants to methadone taken by their mothers is minimal and that women in methadone maintenance programs should not be discouraged from breast feeding because of this exposure.

Yoshida K; Kumar R. Breast-feeding and psychotropic-drugs. International Review of Psychiatry 8(1): 117-124, 1996. (53 refs.)

All commonly used psychotropic drugs pass into breast-milk. Most of the literature consists of single case studies and there is too little information to permit one to reach firm conclusions about the presence of, or lack of, possible risks to infants. In most instances, and particularly in relation to tricyclic antidepressants about which most is known, it seems probable that the benefits of breastfeeding will outweigh the potential and as yet undefined risks to the infants of very small amounts of drugs and their metabolites. Systematic, controlled longitudinal research is needed to check for accumulation of drugs in infants and to exclude both short and long term toxic effects. Such studies may not be justifiable until enough single-case data has accumulated. Recommendations are made to improve the quality of information from single case studies and to prevent infants from being exposed to drugs in breast-milk if there are any concerns about their health and development.

Yoshida K; Smith B; Kumar R. Psychotropic drugs in mothers' milk: A comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding. (review). Journal of Psychopharmacology 13(1): 64-80, 1999. (117 refs.)

Many mentally ill women want to breast-feed their babies but, if they are taking psychotropic drugs, there is very little systematic data upon which to base decisions about whether or not it is safe to do so. We therefore attempt to provide a comprehensive and critical summary of existing case reports and of studies of breast-feeding in relation to commonly used psychotropic drugs. The literature review focuses on the following drugs: antidepressants: tricyclics and serotonin selective reuptake inhibitors (SSRIs); antipsychotic drugs: chlorpromazine, perphenazine, haloperidol and clozapine; mood stabilizers: lithium and carbamazepine; and benzodiazepines. The research literature consists mainly of single case reports and there have been very few attempts at controlled, longitudinal investigations. Findings are often difficult to compare because of differences in methods or because of lack of key information. Most data are available about the tricyclic antidepressants but even here we have found that the reports cover only a grand total of 66 mother- infant pairs. Dilemmas about whether or not to contraindicate breast-feeding arise most commonly in relation to postnatal depression. The findings to date suggest that provided that infants are healthy at the outset it is likely that the benefits of breast-feeding will outweigh potential hazards if their mothers are taking established tricyclic drugs at recommended dose levels. Much less is known about risks associated with SSRI antidepressants or about antipsychotic drugs such as phenothiazines and butyrophenones or mood stabilizers such as carbamazepine, all of which enter breast-milk. Safeguards are suggested for future single case studies, which, as they accumulate, will provide a platform for mounting controlled prospective studies properly to test for any acute toxic effects and for possible long- term adverse effects of such drugs on infants' development. Appendix I is a review of assay methods. Appendix 2 examines pharmacokinetic factors in newborn preterm and sick infants with special reference to contraindications to breast-feeding. Appendix 3 is a review of methods for assessing infant health and development.

Zanardo V; Nicolussi S; Cavallin S; Trevisanuto D; Barbato A; Faggian D et al. Effect of maternal smoking on breast milk interleukin-1 alpha, beta-endorphin, and leptin concentrations. Environmental Health Perspectives 113(10): 1410-1413, 2005. (33 refs.)

Tobacco smoke is immunotoxic, but the effect of smoking on the immunologic function of the mammary gland of mothers who smoke cigarettes ("smoker mothers") has not been studied. Our objective was to test, in smoker mothers, the colostral and transitional milk concentrations of interieukin-(IL)1 alpha. The immunomodulators beta-endorphin and leptin were also tested. Pregnant women who self-identified as smokers (>= 5 cigarettes per day through pregnancy) or nonsmokers were recruited for study participation. The study population included 42 smoker and 40 nonsmoker nursing mothers, with otherwise uncomplicated gestation, delivery, and puerperium, who were breast-feeding ad libitum their healthy neonates. Colostrum was obtained on the third postpartum day at 0900 hr and transitional milk on the 10th postpartum day at 0900 hr. IL-1 alpha concentrations were significantly reduced in the colostrum of smoker mothers compared with nonsmoker mothers (p < 0.01). Colostral P-endorphin and leptin concentrations were comparable. No significant differences were found between smoker and nonsmoker lactating mothers in transitional milk concentrations of IL-1 alpha, beta-endorphin, and leptin. Moreover, P-endorphin and leptin concentrations were significantly reduced in transitional milk samples compared with colostrum of both smoker and nonsmoker mothers (p < 0.05); also, IL-1 alpha transitional milk concentrations were reduced compared with colostrum, but without any significance. This analysis shows that maternal smoking alters the colostral milk levels of the proinflammatory cytokine IL-1 alpha. The altered postnatal provision of alternative source of the proinflammatory cytokine IL-1 alpha adds understanding to how breast-feeding could be nonprotective against infections among the neonates nursed by smoker mothers.

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