Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.

Recomendaciones para el empleo de probióticos en la diarrea en la infancia / Recommendations for the use of probiotics in childhood diarrhea

La pediatría es una de las especialidades médicas donde los ensayos clínicos aleatorizados con probióticos han demostrado la eficacia y seguridad de éstos en diversas patologías, sobre todo digestivas. La mayor evidencia corresponde al empleo de probióticos en diversos tipos de diarreas, por lo que han sido incluidos en diferentes guías de práctica clínica. El efecto del probiótico debe valorarse en función de la cepa utilizada, la dosis y la duración del tratamiento. Los probióticos son eficaces en el tratamiento de la diarrea aguda infecciosa infantil, ya que acortan la duración media del proceso, el número de deposiciones y el porcentaje de episodios que se prolongan más de 4 días. De igual modo, han sido ampliamente estudiados para prevenir el desarrollo de la diarrea asociada a antibióticos, siendo los que tienen mayor nivel de evidencia la levadura (AU)

Pediatrics is one of the medical specialties where randomized clinical trials with probiotics have demonstrated its efficacy and safety in various pathologies, especially digestive being their use in different types of diarrhea, where more evidence there is for what are included in different clinical practice guidelines. The effect of probiotic should be assessed according to the used strain, dose, administration time and the duration of the same. Probiotics are effective in the treatment of acute infectious diarrhea in children by shortening the average duration of the process, the number of liquid stools, and the percentage that lasts more than 4 days. In the same way, have been widely studied for preventing the development of antibiotic-associated diarrhea being those that have higher level of evidence the yeast Saccharomyces boulardii and strain Lactobacillus rhamnosus GG (AU)

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. TRIAL REGISTRATION NUMBER: NCT01111864.

Safety of a dual potential prebiotic system from Mexican agave "Metlin® and Metlos®", incorporated to an infant formula for term newborn babies: a randomized controlled trial.

RATIONALE: Infant formulae are being supplemented with probiotics, prebiotics, or symbiotic despite uncertainties regarding their efficacy. Mexican agave is an interesting source of fructans with particular features and with potential prebiotic effects. MATERIAL AND METHODS: RCT in 600 healthy term babies (20 ± 7 days), allocated to receive standard infant formula (control) or infant formula added with a dual prebiotic system "Metlin® and Metlos®", from Mexican agave. Primary outcomes include stools frequency, stools consistency, gastrointestinal intolerance (frequency of abdominal distension, flatulency, regurgitations, vomiting). Secondary outcomes include changes on weight and height along the study and frequency of dermatologic problems (eczema). RESULTS: In 66,120 days of total follow-up, there were no differences on the frequency of stools passage (Human Milk: 3.8 ± 2.4 evacuations per day; Pro + Metlin + Metlos 3.6 ± 2.0; Pro + Metlin 3.6 ± 2; only Pro 3.4 ± 2.3¸ only formula 3.4 ± 2.0; p NS). Consistency of stools was similar between human milk and prebiotics supplemented groups. Also the frequency of gastrointestinal symptoms was significantly low between these groups. CONCLUSIONS: Fructans derivate from agave and added to infant formula are safe and well tolerated by Mexican healthy term babies.

Antibiotic-associated bloody diarrhea in infants: clinical, endoscopic, and histopathologic profiles.

OBJECTIVE: Antibiotic-associated diarrhea constitutes 1 of the most frequent side effects of antimicrobial therapy with widely varying clinical presentations; however, little is known about its antibiotic-associated bloody diarrhea (AABD) form, particularly in very young children. The aim of this study was to describe the clinical, endoscopic, and histopathologic profiles of community-acquired AABD in infants. PATIENTS AND METHODS: The study included 23 infants referred with bloody diarrhea that developed a few days after receiving antibiotics on an outpatient basis for watery diarrhea (18), respiratory tract infections (4), or urinary tract infection (1). Detailed clinical assessment, videosigmoidoscopy, and histopathologic examination of endoscopic biopsies were performed for all. RESULTS: Clinically, on presentation, bloody diarrhea was acute in all except 1 patient with a prolonged course (for 25 days) and stopped in all 2 to 6 days after discontinuation of antibiotics. Fever and/or leukocytosis were present only in 8 (34.8%). Sigmoidoscopy revealed varying types of erythema (patchy, ring, diffuse) and ulcers (aphthoid, diffuse) in 18 and pseudomembranes in 5. Histopathologically, only 3 showed the characteristic mushroom-like pseudomembranes, whereas all of the other infants had nonspecific colitis. CONCLUSIONS: Community-acquired AABD is not uncommon in infants presenting with acute or chronic forms even without fever or leukocytosis. When suspected, discontinuation of antibiotics is a good policy if facilities for bacterial culture with cytotoxin assays are limited. The characteristic endoscopic or histopathologic pseudomembranes are encountered only in a small percentage (26%). Rational use of antibiotics should be adhered to particularly in cases of watery diarrhea that is mostly of viral origin.

The safety of macrolides during lactation.

BACKGROUND: Infantile exposure to macrolides has been associated with hypertrophic pyloric stenosis causing projectile vomiting, dehydration, electrolyte abnormalities, and in rare cases death possibly via macrolide interaction with gastric motilin receptors. Large population-based cohorts have suggested that exposure to macrolides via breastmilk may be associated with pyloric stenosis. METHODS: In this prospective, controlled observational study designed to assess the safety of macrolides during lactation, we followed infants whose mothers contacted our Drug Consultation Center at the Assaf Harofeh Medical Center (Zerrifin, Israel) inquiring about safety of macrolides during lactation and compared them to a cohort of infants exposed to amoxicillin during breastfeeding. RESULTS: Fifty-five infants exposed to macrolide antibiotics were compared to a control cohort of 36 infants exposed to amoxicillin via lactation. The infants in the macrolide group were all exposed to erythromycin and the newer macrolides: azithromycin, clarithromycin, and roxithromycin. The rate of adverse reactions the infant experienced while being exposed to both antibiotics was comparable. Seven (12.7%) infants in the macrolide group experienced adverse reactions versus three infants (8.3%) in the amoxicillin group (odds ratio = 1.6, 95% confidence interval, 0.38-6.65, p = 0.73). The adverse reactions in the infants exposed to macrolides were rash, diarrhea, loss of appetite, and somnolence, whereas the infants exposed to amoxicillin experienced rashes and somnolence. Factors such as gestational age, age and weight at exposure, maternal age, or type of macrolide were not associated with the infant's adverse reaction in multivariate regression analysis. CONCLUSIONS: Rates and types of minor adverse reactions in breastfed infants exposed to a macrolide or amoxicillin in breastmilk were comparable. Macrolide exposure during breastfeeding was not associated with pyloric stenosis, although larger prospective studies are required to confirm our observation.

Side effects of oral misoprostol for the prevention of postpartum hemorrhage: results of a community-based randomised controlled trial in rural India.

OBJECTIVE: To investigate the side effects of 600 microg oral misoprostol given for the mother and the newborn to prevent postpartum hemorrhage (PPH). METHODS: One thousand six hundred twenty women delivering at home or subcentres in rural India were randomised to receive misoprostol or placebo in the third stage of labour. Women were evaluated for shivering, fever, nausea, vomiting and diarrhea at 2 and 24 h postpartum. Newborns were evaluated within 24 h for diarrhea, vomiting and fever. Symptoms were graded as absent, mild-to-moderate or severe. RESULTS: Women who received misoprostol had a significantly greater incidence of shivering (52%vs. 17%, p < 0.001) and fever (4.2%vs. 1.1%, p < 0.001) at 2 h postpartum compared with women who received placebo. At 24 h, women in the misoprostol group experienced significantly more shivering (4.6%vs. 1.4%, p < 0.001) and fever (1.4%vs. 0.4%, p < 0.03). There were no differences in nausea, vomiting or diarrhea between the two groups. There were no differences in the incidence of vomiting, diarrhea or fever for newborns. CONCLUSIONS: Misoprostol is associated with a significant increase in postpartum maternal shivering and fever with no side effects for the newborn. Given its proven efficacy for the prevention of PPH, the benefits of misoprostol are greater than the associated risks.

The safety of amoxicillin/clavulanic acid and cefuroxime during lactation.

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

Copper in drinking water: not a strong risk factor for diarrhoea among young children. A population-based study from Sweden.

AIM: To assess whether mean daily intake of copper or maximal concentration of copper in drinking water is related to the incidence of diarrhoea and vomiting among young children. METHODS: Mean daily intake of copper from drinking water was estimated prior to episodes of diarrhoea among 430 children aged 9 to 21 mo. A total of 4703 samples of tap water were collected in the homes of the children. The mean daily intake of copper and the maximal concentration of copper in samples of consumed water were used as measures of exposure. The cumulative incidence of acute diarrhoea and vomiting was studied during 12 wk of follow-up. Cases of diarrhoea caused by viral and bacterial infections were identified. RESULTS: The median copper level of the mean value for each child was 0.61 mg/L with 10th and 90th percentiles of 0.04 and 1.57 mg/L. Among the 430 children, 43 had episodes of acute diarrhoea, of which 23 had no identified viral or bacterial origin, and vomiting was reported in 95 children. No significant associations were found between daily intake of copper or maximal concentration of copper in drinking water and the risk of diarrhoea or vomiting. CONCLUSION: There is unlikely to be a strong association between daily intake of copper or maximal concentration of copper in drinking water and the risk of diarrhoea or vomiting within the range of copper intakes/concentrations studied.

Symptoms of mothers and infants related to total volatile organic compounds in household products.

The authors sought to determine whether reported symptoms of mothers and infants were associated significantly with the use of household products that raised indoor levels of total volatile organic compounds (TVOCs). Data collected from 170 homes within the Avon Longitudinal Study of Parents and Children (ALSPAC: a large birth cohort of more than 10,000) had determined which household products were associated with the highest levels of TVOCs. The latter data were collected over a period that approximated 6 mo of pregnancy and the infants' first 6 mo of life. This paper presents (a) the mothers' self-reports of the use of these products in their homes and (b) self-reported medical symptoms of mothers and infants postnatally. Higher TVOC levels were associated with air freshener and aerosol use. Infant diarrhea and earache were statistically significantly associated with air freshener use, and diarrhea and vomiting were significantly associated with aerosol use. Headache experienced by mothers 8 mo after birth was significantly associated with the use of air fresheners and aerosols; maternal depression was significantly associated with the use of air fresheners. The results of the study suggest a link between the use of products that raise indoor levels of TVOCs and an increased risk of certain symptoms among infants and their mothers.

Randomized clinical trial of soy formula with and without added fiber in antibiotic-induced diarrhea.

OBJECTIVE: The objective of this study was to examine the effects of soy formulas with and without added soy fiber in children who developed diarrhea while receiving antibiotics. DESIGN: In a masked, randomized parallel study, older infants and toddlers were fed commercial soy formulas with or without added soy fiber for 10 days on occurrence of diarrhea during the administration of antibiotics. Subjects were stratified by feeding (formula versus cow's milk). The primary variables were duration of diarrhea, stool characteristics, and intake. Secondary variables were weight and spit-up. RESULTS: All 45 children who completed the 10-day study received >30% of their caloric intake from formula. Fiber intake from other foods did not differ between groups and averaged 0.5 g/day. Total median fiber intake of the group fed the formula with added fiber was 6.53 g/day. The mean duration of diarrhea was 25.1 +/- 5.2 hours for children fed the formula with added fiber and 51.6 +/- 10.7 hours for those fed the regular formula (P =.0013). CONCLUSION: The duration of antibiotic-induced diarrhea in children fed the soy formula with added soy fiber was significantly reduced.

Malabsorption of modified food starch (acetylated distarch phosphate) in normal infants and in 8-24-month-old toddlers with non-specific diarrhea, as influenced by sorbitol and fructose.

UNLABELLED: Acetylated distarch phosphate (ADiSP) is a modified starch used in some baby foods. The bioavailability of ADiSP and a native (unmodified) starch was evaluated in 20 normal infants and 21 toddlers aged 8-24 mo with chronic non-specific diarrhea. Formulae contained 8% native or 8% modified waxy maize starch. No infant or toddler consuming Formula N (native starch) had elevated peak breath hydrogen levels (20 ppm or greater), stools clinically positive for reducing substances (0.75% or greater) or loose stools. Fourteen infants received formula M (modified starch): 2 had elevated breath hydrogen, 1 had positive stools and another had loose stools. Of the 21 toddlers fed formula M, 2 had elevated breath hydrogen, but none had positive stools or loose stools. Formula NS (native starch with 2% sorbitol) had little effect on breath hydrogen in the infants but significantly increased it in the toddlers. Formula NS produced loose stools in 2 toddlers but no clinically positive stools in any infant or toddler. Formula MS (modified starch with 2% sorbitol) elevated breath hydrogen in 3 infants and 8 toddlers, and produced positive stools in 2 infants and 2 toddlers, and loose stools in 4 infants and 7 toddlers. Formula MSF (modified starch with 2% sorbitol and 5% fructose) elevated breath hydrogen in 7 infants and 10 toddlers, positive stools in 7 infants and 6 toddlers, and loose stools or diarrhea in 7 infants and 11 toddlers. CONCLUSION: ADiSP modified starch can increase breath hydrogen and produce loose stools. Sorbitol and fructose aggravate the malabsorption, in some cases leading to frank diarrhea.

Epidemiological features of rotavirus infection in Caracas, Venezuela: implications for rotavirus immunization programs.

The epidemiological features of rotavirus infection may be quite relevant for evaluation of the performance of a rotavirus vaccine in different settings, as well as for monitoring its impact during vaccination under routine conditions. This article describes some important issues regarding rotavirus epidemiology in Venezuela, where major field trials of rotavirus vaccine have been carried out. Rotaviruses was significantly more frequently observed in inpatient (43%) than in outpatient (21%) consultations for diarrhea in infants and young children. There was a high prevalence of rotavirus illness, regardless of socioeconomic conditions, but the risk of dehydration was greater among the lower socioeconomic groups. Rotavirus disease occurs year-round, with a slight seasonal pattern. Eighty-five percent of rotavirus-positive diarrheal episodes, as well as 86% of cases of dehydration due to rotavirus, occurred during the first year of life. However, rotavirus illnesses occur less commonly during the first months of life (0-2 months), which may be a result of protection by transplacental antibodies. The pattern of acquisition of rotavirus antibody was consistent with this age distribution of disease and with optimal age for vaccination. Thus, regional epidemiological characteristics of rotavirus infection may affect optimal performance of rotavirus vaccine.

Risk of diarrhea related to iron content of infant formula: lack of evidence to support the use of low-iron formula as a supplement for breastfed infants.

BACKGROUND: Concern has been raised by infant feeding experts that supplementing breastfed infants with iron-fortified formula rather than low-iron formula may have an undesirable impact on their gastrointestinal flora. Thus far, there have been no clinical studies to address this issue directly. We compared the reported frequency of diarrhea for breastfed infants given iron-fortified formula with those fed low-iron formula. METHODS: Mothers participating in a mail panel provided feeding and diarrhea information on their infants at 2, 3, 4, 5, 6, 7, 9, and 12 months (n = 1743). Infants were grouped into five feeding categories: (1) breast milk only, (2) breast milk and low-iron formula, (3) breast milk and iron-fortified formula, (4) low-iron formula only, and (5) iron-fortified formula only. We calculated the number of diarrheal episodes per week for each feeding category and used rate ratios to estimate the relative impact of low-iron and iron-fortified formulas. RESULTS: Among infants who received both breast milk and formula, the rate ratio for iron-fortified formula versus low-iron formula was 1.06 (confidence interval, 0.84 to 1.34), indicating that the type of formula a breastfed infant receives does not significantly affect the frequency of diarrhea. CONCLUSIONS: We found no evidence to support the hypothesis that breastfed infants given iron-fortified formula are at greater risk of having diarrhea. This, in addition to the fact that iron-fortified formula has played a major role in preventing childhood iron deficiency anemia, supports the current recommendation that any formula given to infants be fortified with iron.

[Abuse of artificial sweetener as differential diagnosis of lactose intolerance]. / Süssstoffabusus als Differentialdiagnose der Laktoseintoleranz.

A two year old dystrophic boy with chronic diarrhea was described. At the age of 6 month the boy developed a severe gastroenteritis with a secundary lactase deficiency. Dietary treatment was however not successful and consequently the boy became dystrophic. At last, an abuse of sweetener was diagnosed.

High levels of inorganic sulfate cause diarrhea in neonatal piglets.

Artificially reared neonatal piglets were used to study the effect of inorganic sulfate on bowel function in human infants. Two experiments were conducted to evaluate the effect of high levels of inorganic sulfate on the growth, feed intake and feces consistency of artificially reared piglets, and to determine the dose at which at least 50% of piglets develop nonpathogenic diarrhea. The effect of sulfate level on kidney weight and concentration of inorganic sulfate in urine was also assessed. In each experiment, 40 pigs with an average initial age of 5 d were individually caged and reared with an automatic feeding device. Ten pigs per dietary treatment were fed one of four diets containing the following levels of added inorganic sulfate (mg/L of diet), as anhydrous sodium sulfate (USP): 0, 1200, 1600 and 2000 for Experiment 1 (18-d study), and 0, 1800, 2000 and 2200 for Experiment 2 (16-d study). The levels of added sulfate did not affect (P > 0.05) the growth of piglets, or their feed intake. Whereas 1200 mg added sulfate/L had essentially no effect on feces consistency, levels > 1800 mg/L of diet resulted in a persistent, nonpathogenic diarrhea in neonatal piglets. Added sulfate did not affect (P > 0.05) relative kidney weight. Inorganic sulfate in urine reached maximum concentration (P < 0.05) in pigs fed diets with 1600 and 1800 mg added sulfate/L in Experiments 1 and 2, respectively, but declined at higher levels. The results suggest that the level of added dietary inorganic sulfate at which 50% of piglets develop nonpathogenic diarrhea is between 1600 and 1800 mg/L.

Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.

Effect of counseling on maternal reporting of adverse effects in nursing infants exposed to antibiotics through breast milk.

In a recent trial, we found that nursing women reported diarrhea in their nursing infants after maternal use of antibiotics. However, because they were told that this could occur during a medication counseling session, the observed effect could have been due to a reporting bias. The objectives of this study were to determine if counseling nursing women about side effects of antibiotic they used could (a) influence the adverse event reporting rate or (b) influence maternal nursing and medication compliance behavior. In a randomized, controlled trial, nursing women calling a teratogen information service for advice about selected antibiotics received one of two possible counseling formats (A and B). Both groups were informed that the antibiotics were safe to use. Mothers in group B were also informed about a theoretical risk of diarrhea in the infant. Mothers later reported clinical events they noted in the infants and judged whether they were due to the antibiotic. Eighty-seven percent (54/62) of group A subjects compared to 68% (52/76) of group B subjects reported clinical events in their infants during their antibiotic therapy (P = 0.017). The incidence of reported diarrhea was 26% in group A compared to 17% in group B (P = 0.3); 34% of subjects in both groups attributed clinical events to antibiotic therapy (P = 1.0). Diarrhea was attributed to antibiotic therapy in 13% of group A and 12% of group B subjects (P = 1.0). No differences were observed between groups in breastfeeding pattern and antibiotic compliance. Breastfeeding women counseled about adverse effects were not more likely to report side effects in their infants or to change nursing behavior and medication compliance.