Abstract
Aim
We aimed to investigate plasma lamotrigine concentrations and clinical effects in infants exposed to lamotrigine through breastfeeding.
Methods
This was a retrospective study of mother–infant dyads in a clinical follow‐up programme in Stockholm, Sweden. Data were collected from medical records.
Results
We included 47 breastfed infants, born from 2011 to 2021, with a median gestational age of 39 + 6 weeks/days and a median birth weight of 3420 g. The median lamotrigine concentration in the infants' plasma was 2.5 (range 2.5–14.0) μmol/L. These concentrations correlated significantly with both the maternal plasma concentrations and the maternal doses (R = 0.79, p < 0.001 versus R = 0.54, p < 0.001). During the follow up, lamotrigine concentrations within the reference range for epilepsy treatment were detected in six (14%) infants and one had clinical symptoms that were probably related to lamotrigine exposure. Liver transaminases were elevated in three of 21 infants. All infants whose mothers had a dose of 150 mg or less had undetectable plasma concentrations and no symptoms during follow up.
Conclusion
Infants exposed to lamotrigine through breastfeeding had a low risk of toxic effects. All infants whose mothers had low lamotrigine doses had unmeasurable plasma concentrations and no symptoms of lamotrigine exposure. These low‐risk infants might be offered a simplified follow up.
Keywords: breastfeeding, infant, lamotrigine concentration, liver transaminases, toxic effects
Abbreviations
- ALT
alanine aminotransferase
- AST
aspartate transaminase
Key notes.
This study aimed to investigate plasma lamotrigine concentrations and clinical effects in 47 infants exposed to lamotrigine through breastfeeding.
The lamotrigine concentration in the infants' plasma correlated significantly with both the maternal plasma concentrations and the maternal doses.
Breastfed infants exposed to lamotrigine had a low risk of toxic effects and all infants whose mothers had doses of 150 mg or less had unmeasurable plasma concentrations and no symptoms of exposure.
1. INTRODUCTION
Lamotrigine has a low teratogenic potential and is therefore the most frequently prescribed drug for epilepsy during pregnancy. Furthermore, it is being increasingly used in the treatment of bipolar disorder. 1 , 2 Breastfeeding has multiple benefits for both mothers and babies, and many women treated with lamotrigine wish to breastfeed their infants. 3 Lamotrigine passes into breast milk in moderate amounts. Together with the infant's limited capacity to metabolise lamotrigine, this may result in considerable serum concentrations in the breastfed neonate. 4 , 5 , 6 The long‐term outcomes after exposure to lamotrigine through breastfeeding seem reassuring, but adverse short‐term effects have been described. 6 , 7 , 8 , 9 Around 100 infants exposed to lamotrigine through breastfeeding, without adverse effects, have been reported. However, three cases with serious outcomes have been reported. 10 , 11 , 12 , 13 In one of these cases, the infant was exposed to two other psychotropic drugs in addition to lamotrigine. Fatigue, elevated liver transaminases, rash and affected platelets are among the reported adverse effects in infants exposed to lamotrigine by breastfeeding. 6 , 7 , 8 , 9 These effects have caused controversy around breastfeeding, with some healthcare providers discouraging mothers from breastfeeding during lamotrigine treatment. More knowledge is needed about how to prevent these adverse effects and monitor infants, in order to facilitate safe breastfeeding.
The first aim of this study was to analyse plasma lamotrigine concentrations and clinical outcomes in infants exposed to lamotrigine through breastfeeding, stratified according to maternal dose. The second aim was to identify factors associated with a low risk of adverse effects in the same group of infants.
2. PATIENTS AND METHODS
2.1. Study design
The study was a retrospective observational cohort study. The data were collected from the medical records of the mothers and infants participating in the study. The main outcomes were infant lamotrigine plasma concentrations and clinical outcomes, stratified according to maternal dose. The secondary outcome was liver transaminase levels in the exposed infants.
2.2. Subjects
Infants exposed to lamotrigine through breastfeeding were identified via diagnostic codes in medical records in two hospitals in Stockholm, Sweden. The study periods were from 23 September 2018 to 11 May 2021 at the Karolinska University Hospital and from 2 March 2011 to 14 November 2018 at the Sachs' Children and Youth Hospital.
2.3. Clinical follow‐up programme
Pregnant women, who wished to breastfeed their infants and who lacked medical contraindications, were enrolled in the clinical follow‐up programme that Karolinska University Hospital initiated in 2018. This programme comprised check‐ups at birth and at two, four and 8 weeks of age. Lamotrigine concentrations and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested in infant plasma and a clinical examination was performed. If there were any abnormal laboratory results or clinical findings, the mother was instructed to reduce or discontinue breastfeeding. A follow‐up programme had been running at the Sachs' Children and Youth Hospital since 2011. This featured a similar structure of clinical and laboratory follow ups, but without ALT or AST tests. It was based on a predefined checklist (Table S1).
2.4. Data collection
Throughout the study period, lamotrigine plasma concentrations were analysed with the Quantitative Microsphere System lamotrigine immunoassay (Thermo Scientific). The concentrations were measured in μmol/L and the detection limit for lamotrigine in plasma was 5 μmol/L. Plasma lamotrigine concentrations of 10–59 μmol/L were considered to be within the reference range for treating epilepsy. 14 At Sachs' Children and Youth Hospital, the infant and maternal blood samples were collected simultaneously. The mothers had been advised to not take their morning dose of lamotrigine before they were tested and the samples were considered to be trough concentrations. The infants' concentrations were generally sampled before noon at Karolinska University Hospital, and these mothers had also been advised not to take their morning lamotrigine dose that day. The Hospital did not measure maternal lamotrigine concentrations at the follow‐up visits. Instead, the concentrations used for this study were obtained from the mothers' own physicians. These were also assumed to be trough levels, as they had been sampled in the mornings, according to clinical routines. The timing of the infant blood samples was not standardised in relation to breastfeeding.
Data on maternal background characteristics were obtained from medical records between 7 June and 30 September 2022. These were diagnoses, medication, plasma lamotrigine concentrations and delivery outcomes, as well as data on infant growth, laboratory parameters and clinical outcomes. The variables are presented in Tables 1 and 2 and in Table S2.
TABLE 1.
Background characteristics of the 47 mother–infant dyads who took part in the study.
| Median (range) | Missing, n (%) | |
|---|---|---|
| Maternal age | 32 (20–44) | – |
| Parity | 1 (1–4) | 1 (2) |
| Body mass index, first trimester | 23.0 (18.0–34.9) | 18 (38) |
| Gestational age at birth (weeks/days) | 39 + 6 (36 + 2–42 + 1) | – |
| Infant birth weight (grams) | 3420 (2910–4850) | – |
| Apgar score at 1 min | 9 (2–10) | – |
| Apgar score at 5 min | 10 (6–10) | – |
| n (%) | Missing, n (%) | |
|---|---|---|
| Infant sex female | 32 (68) | – |
| Singleton pregnancy | 47 (100) | – |
| Maternal diagnosis | – | |
| Epilepsy | 30 (64) | |
| Bipolar disorder type 1 | 1 (2) | |
| Bipolar disorder type 2 | 14 (30) | |
| Unipolar depression | 1 (2) | |
| Psychosis | 1 (2) | |
| Concurrent psychotropic medication at time of delivery | 14 (30) | 2 (4) |
| Concurrent psychotropic medication at first follow up | 9 (19) | 4 (9) |
| Smoking and use of snuff before pregnancy | 8 (17) | 14 (30) |
| Smoking and use of snuff during first trimester | 1 (2) | 14 (30) |
| Drank alcohol 3 months before pregnancy | 18 (38) | 24 (51) |
| Drank alcohol during first trimester | 0 (0) | 15 (32) |
| Illicit drug use 3 months before pregnancy | 1 (2) | 14 (30) |
| Illicit drug use during first trimester | 0 (0) | 14 (30) |
| Maternal employment before pregnancy | 7 (15) | |
| Full‐time | 25 (53) | |
| Part‐time | 9 (19) | |
| Unemployed or not working | 6 (13) | |
| Living with infant's father during the first trimester | 42 (89) | 1 (2) |
TABLE 2.
Lamotrigine plasma concentrations and infant outcomes by exposure group.
| Maternal dose of lamotrigine at first follow‐up visit | p a | |||
|---|---|---|---|---|
| 50–150 mg (n = 11) | 200–275 mg (n = 16) | 300–800 mg (n = 20) | ||
| Maternal dose of lamotrigine, mg/day | ||||
| At delivery, median (range) | 100 (50–400) | 275 (200–1200) | 575 (300–1000) | <0.001 |
| At first follow‐up visit, median (range) | 100 (50–150) | 200 (200–275) | 425 (300–800) | <0.001 |
| Background characteristics and breastfeeding | ||||
| Age at first follow‐up visit in days, median (range) | 15 (10–118) | 16 (8–69) | 14 (7–25) | 0.22 |
| Exclusive breastfeeding from start, n/N (%) | 5/11 (46) | 8/15 (53) | 11/20 (55) | 0.93 |
| Exclusive breastfeeding at follow up, n/N (%) | 6/11 (55) | 12/15 (80) | 14/19 (74) | 0.71 |
| Taking other psychotropic medications concurrently, n/N (%) | 1/9 (9) | 4/15 (27) | 4/19 (21) | 0.89 |
| Plasma lamotrigine concentrations at the first follow‐up visit | ||||
| Mother (μmol/L), median (range) | 7 (2.5–14.9) | 14.1 (8–13.2) | 19.2 (7.2–44.7) | <0.05 |
| Infant (μmol/L), median (range) | 2.5 (2.5–2.5) | 2.5 (2.5–8.2) | 2.5 (2.5–11.2) | <0.05 |
| Infants with unmeasurable lamotrigine concentrations, n/N (%) | 9/9 (100) | 9/13 (69) | 10/20 (50) | <0.05 |
| Infant/mother ratio, median (range) | 0.34 (0.17–0.45) | 0.27 (0.12–0.33) | 0.24 (0.09–0.55) | 0.60 |
| Plasma lamotrigine concentrations at the second follow‐up visit | ||||
| Mother (μmol/L), median (range) | 11.3 (7.9–16.0) | 13.6 (9.0–36.3) | 28.0 (12.8–44.5) | <0.05 |
| Infant (μmol/L), median (range) | 2.5 (2.5–2.5) | 2.5(2.5–9.0) | 6.9 (2.5–12.2) | <0.05 |
| Infants with unmeasurable lamotrigine concentrations, n/N (%) | 6/6 (100) | 10/14 (71) | 5/17 (29) | <0.05 |
| Infant/mother ratio, median (range) | 0.22(0.16–0.32) | 0.22 (0.09–0.31) | 0.30 (0.17–0.40) | 0.06 |
| Clinical outcomes | ||||
| Symptoms at birth, n/N (%) | 0/10 (0) | 6/16 (38) | 7/19 (37) | <0.05 |
| Symptoms during follow up, n/N (%) | 0/11 (0) | 2/16 (13) | 6/19 (32) | 0.07 |
| Elevated ALT levels during follow up, n/N (%) | 0/4 (0) | 1/8 (13) | 2/9 (22) | 1.00 |
Abbreviations: n, number of infants in the group with the outcome; N, number of infants tested in the group.
p for difference between the groups, calculated with the Kruskal–Wallis and chi‐square tests.
2.5. Data analysis
For the stratification, the infants were divided into three groups based on the daily maternal lamotrigine dose: ≤150 mg or less, >150–275 mg and >275 mg. The infant/mother ratios were calculated by dividing the lamotrigine concentration in the infant plasma with the concentration in the maternal plasma. The maternal plasma concentration was considered to be in a steady state when the maternal dose had not changed for 7 days. 15 The maternal and infant concentrations that were measured closest in time to each other, but no more than 12 days apart, were used to calculate the ratios. 16 A mock value of 2.5 μmol/L was used for concentrations below 5 μmol/L. 17 , 18 Infant weight gain was considered to be inadequate if it was below the 90th percentile of the weight nomogram. For infants below 30 days of age, the growth chart from Flaherman et al. was used, 19 while the World Health Organisation chart was used for older infants. 20 Breastfeeding was categorised as exclusive or partial.
2.6. Statistical analysis
Continuous data were presented as medians and ranges due to the small sample size. The means and standard deviations for these variables are presented in Table S3. The categorical variables were presented as numbers and percentages. The chi‐square test was used to determine differences between independent groups. The Wilcoxon Signed Rank test was used to determine differences between related samples of categorical variables and the Kruskal–Wallis test was used for differences between continuous variables. Correlations between continuous variables were assessed with Spearman's correlation coefficients. All statistical tests were two‐sided and p < 0.05 was considered to be statistically significant. SPSS Software Statistics for Windows, Version 28.0.1.1 (IBM Corp) was used for all the statistical analyses.
3. RESULTS
Using diagnostic codes, we identified 61 mother–infant dyads with lamotrigine exposure during breastfeeding and received parental informed consent to include 47 dyads (Figure 1). All the included infants had also been exposed to lamotrigine during pregnancy. One infant was diagnosed with Turner syndrome and was therefore excluded from the analysis of symptoms during follow up.
FIGURE 1.
Flowchart of included patients.
3.1. Maternal characteristics
Of the 47 mothers who were included, 30 (64%) had been prescribed lamotrigine for epilepsy and 17 (36%) for a psychiatric disorder (Table 1). The daily maternal lamotrigine dose was significantly lower at the first follow up (median 200 mg, range 50–800 mg) than at the time of delivery (median 400 mg, range 50–1200 mg, p < 0.001). The largest decrease in the median dose, of 150 mg/day, was seen in the group with the highest doses at the first follow up (Table 2). One‐third of the women were concurrently taking other psychoactive drugs at the time of delivery and one‐fifth were doing so at the first follow‐up visit. In most cases, sedatives and anxiolytics were discontinued postpartum (Table 1).
3.2. Infant characteristics
The background infant characteristics are presented in Table 1. Of the included infants, 17 (36%) were born by Caesarean section and the rest were vaginally. One infant was born late preterm, at 36 + 2 weeks/days of gestational and three infants were large for gestational age. The others were born at term and appropriate for gestational age. Around two‐thirds of the infants were exclusively breastfed until at least 2 months of age (Table S4).
3.3. Infant lamotrigine concentrations
A total of 93 concentrations were measured in 44 infants during follow‐up visits and maternal lamotrigine doses were available at the time of sampling for 88 of these (Figure 2). A median of two (range 0–4) concentrations were measured for each infant. The median lamotrigine concentration in the infant plasma samples was 2.5 μmol/L (range 2.5–14.0 μmol/L). The infant lamotrigine concentrations correlated significantly with the maternal doses (R = 0.54, p < 0.001) and the maternal plasma concentrations (R = 0.79, p < 0.001) (Figure S1, Table S5). The correlation with the maternal plasma concentrations was somewhat higher (R = 0.84, p < 0.001) when the cohort was restricted to the 44 mothers and infants whose concentrations were sampled simultaneously. There was no significant difference in correlations between samples taken at 2 or 4 weeks postpartum and those taken later. The lamotrigine concentrations decreased with infant age, with the highest levels measured during the first 2 weeks (Table 2, Figure S2). Of all the concentrations, seven (8%) samples from six infants (14%) were within the reference range for epilepsy treatment, while 53 concentrations (57%) were below the detection level (Figure 2, Table 3, Figures S1 and S2).
FIGURE 2.
Boxplots of maternal and infant plasma lamotrigine concentrations, categorised by the maternal daily dose of lamotrigine. n, number of mothers/infants in each dose category.
TABLE 3.
Cases with high lamotrigine concentrations during follow up.
| ID | Lamotrigine concentration (μmol/L) | Maternal lamotrigine dose | Breastfeeding | Infant symptoms | Other PT drugs | Potential cause of pathology | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| IP‐B | IP‐FU | MP‐FU | At birth | At FU | At birth | At FU | At birth | At FU | |||
| A | – | 10.3–11.6‐5 | 26.6–28.8‐30.5 | 700 | 500‐ >450 | Part. | Excl. | No | No | No | High p‐lamotrigine in the infant at the second follow up. The mother reduced breastfeeding to 50%; the infant p‐lamotrigine concentration went from 11.6 to 5 at the third follow up. No adverse symptoms reported. |
| B | – | 8.4–10.9‐7.2 | 28.4–27.3‐31 | 600 | 450 | Excl. | Excl. | No | No | No | High p‐lamotrigine (10.9) in the infant at second follow up. The mother reduced breastfeeding to 75%. The infant's p‐lamotrigine concentration was 7.2 at the third follow up. |
| C | – | 9.2–10.3‐7 | 1000 | 700‐ >600 | Part. | Excl. | No | Inadequate growth at second follow up | No | High infant p‐lamotrigine concentration and slightly inadequate growth (+14 g/day) at the second follow up. The mothers' dose was then reduced. At the third follow up, growth was adequate (+21 g/day) and the infant lamotrigine concentration was lowered. | |
| D | – | 10.0–8.1‐ | 18.3–31.1 | 800 | 400 | Excl. | Excl. | No | Inadequate growth at first follow up | No | The mother reported problems with latching on at the first follow up. This was presumed to be the reason for inadequate growth. At the second follow up, the infant was being exclusively breastfed, and growth was normal. No other symptoms were reported. |
| E | ND | 11.2–9.1 | 37.3 | 475 | 400 | Part. | Excl. | Ventilated for 7 min at birth; Apgar 4–6‐9. Transient jitteriness at examination. | No | SSRI | Mild asphyxia at birth; transient jitteriness assessed as related to SSRI abstinence. High infant p‐lamotrigine concentration at follow up; it decreased when the mother's dose was reduced. No adverse symptoms in the infant reported during follow up. |
| F | – | 9.5–12.2 | 36.9–32.7 | 525 | 400‐ >350 | Excl. | Excl. | Tired at pre‐discharge examination | Hypotonic and tired at second follow up | No | Found to be hypotonic and tired at second follow‐up visit and needed hospitalisation. Infant p‐lamotrigine was 12.2 and examination was otherwise normal. The p‐lamotrigine concentration was found to be the most likely cause of the symptoms. |
Abbreviations: Excl, exclusive; IP‐B, infant plasma at birth, from umbilical cord or within 2 days after birth; IP‐FU, infant plasma at follow up; MP‐FU, maternal plasma at follow up; ND, not detectable; p, plasma; Part, partial; PT, psychotropic; SSRI, selective serotonin reuptake inhibitor.
3.4. Maternal lamotrigine concentrations and infant‐mother ratios
A total of 77 maternal plasma lamotrigine concentrations were measured during follow up: 61 were relatable to, and 44 were taken simultaneously, with the infants' samples. The median maternal lamotrigine concentration was 16.9 μmol/L (range 2.5–44.7 μmol/L). Boxplots of the maternal and infant lamotrigine plasma concentrations, categorised by maternal dose, are presented in Figures 2 and S3. The median infant‐mother ratio was 0.26 (range 0.09–0.55). The ratio did not change markedly when we only analysed concentrations sampled simultaneously and only dyads with measurable infant concentrations.
3.5. Clinical outcomes
After we excluded the infant with Turner syndrome, we were able to analyse the clinical symptoms of 46 infants. These infants were 7–26 days old at the time of the first follow up, with the exception of two, who were included in the study at 69 and 118 days of age. During the follow up, eight (17%) infants presented with clinical symptoms that were potentially connected to the lamotrigine exposure. Five had inadequate growth, two had feeding problems and one had more serious signs of toxic effects, which are described below (Table 3). Advice was given to four mothers (9%) to reduce breastfeeding. In two cases this was because the lamotrigine concentrations were within the epilepsy treatment reference range and both were asymptomatic. In addition, one infant had elevated liver transaminases and one suffered suspected toxic effects (Table 3). Thirteen infants (28%) were reported to have symptoms at birth (Table S6).
3.6. The infant with signs of toxic effects
One infant, listed as patient F in Table 3, presented with hypotension and fatigue at 43 days of age and was admitted to the Hospital. At this time, the infant's plasma lamotrigine concentration was 12.2 μmol/L, the mother's concentration was 32.7 μmol/L and the maternal dose was 350 mg. The mother was being treated exclusively with lamotrigine. No alternative cause of the symptoms was found on examination, and they resolved after breastfeeding was discontinued. It later emerged that this infant had also been described as tired at birth.
3.7. Liver transaminases
Liver transaminases were measured in 21 infants. All the AST levels were within the normal range (<1.4 μkat/l). Three infants (14%) had elevated ALT levels of more than 0.85 μkat/l (range 0.86–1.65) μkat/l during follow up (Table S7).
3.8. Dose stratification
The mother–infant dyads were divided into three groups to identify a group of low‐risk infants, based on the maternal lamotrigine dose at the first follow up (Table 2). All 11 infants whose mothers had a dose of 150 mg or less were seemingly unaffected by the exposure. Their lamotrigine plasma concentrations were undetectable, and they had no clinical symptoms or elevated liver transaminases. In the group with the highest doses (≥300 mg), six infants out of 19 (32%) presented with clinical symptoms during follow up. However, the frequency of the clinical symptoms at follow up did not differ significantly between the groups (Table 2). At birth, the infants exposed to maternal doses of 150 mg or less had significantly fewer clinical symptoms than those exposed to higher doses (Table 2).
4. DISCUSSION
This retrospective study of 47 infants exposed to lamotrigine during breastfeeding found that their plasma lamotrigine concentrations correlated with their mothers' doses and plasma concentrations. One infant, who had a plasma concentration within the reference range for epilepsy treatment, showed signs of toxic effects that disappeared when breastfeeding was discontinued. On the other hand, none of the infants exposed to maternal doses of 150 mg or less had detectable lamotrigine concentrations or clinical symptoms, at birth or during follow up. To our knowledge, this study was the first to investigate infant plasma lamotrigine concentrations and clinical outcomes in a cohort that was monitored within a clinical follow‐up programme.
Our finding that the infant plasma concentrations correlated with the maternal doses and plasma concentrations agreed with previous studies. This might be helpful when determining the risks for exposed infants in the future. 17 , 18 The clinical symptoms at birth were significantly correlated to the maternal doses, but dose‐dependency could not be verified during follow up. There was a trend towards more symptoms among infants whose mothers had the highest doses, but the difference between the groups was not statistically significant. The absence of dose‐dependency regarding symptoms was reassuring and may be explained by the fact that the studied symptoms were common among newborn infants. The most frequently described symptom, poor weight gain, was reported in 11% of the infants, which was similar to the rate in healthy neonates in other studies. 19 , 20 However, one infant, whose lamotrigine concentration lay within the reference range for epilepsy treatment, presented with serious symptoms that were similar to two previously described cases. 11 , 12 A toxic threshold for infant lamotrigine concentrations has not been defined. However, according to the Naranjo probability scale of drug toxicity, these symptoms were probably caused by the drug exposure. 21 This highlights the need for a structured follow‐up programme for infants exposed to lamotrigine through breast milk.
In this cohort, all the mothers of infants with plasma lamotrigine concentrations within the reference range for epilepsy treatment had a dose of 350 mg or more. The infants exposed to maternal doses of 150 mg or less were seemingly unaffected by the exposure, in line with the results of a previous study that reported on infants born to mothers who took lower doses. 22 Therefore, we recommend that special attention be devoted to infants whose mothers are treated with higher doses or have high plasma concentrations. On the other hand, infants born to mothers with lower doses could be offered a simplified follow‐up programme.
Three infants in our cohort had elevated ALT levels. This has been described previously, but contradictory results have also been reported. 6 , 8 , 9 The elevation in ALT levels did not seem to be dose‐dependent and all levels normalised with time. The elevated ALT levels might have been due to reference ranges not being adapted to infants. Alternatively, they might have reflected the somewhat higher ALT levels occurring naturally in breastfed infants. 23 , 24 These three infants might have also had undiagnosed cytomegalovirus infections, which are commonly transmitted through breast milk. 25 We conclude that the number of infants whose liver transaminases were analysed was limited and that larger cohorts are needed to confirm or refute a correlation between lamotrigine exposure and elevated liver transaminases.
4.1. Strengths and limitations
This study had several strengths. We undertook repeated measurements of infant lamotrigine plasma concentrations and related them to clinical symptoms, as well as to maternal doses and plasma concentrations. The number of infants in the study was, to our knowledge, one of the largest reported so far. The fact that the study focused on all infants exposed to lamotrigine through breast milk, not only those suffering adverse effects, is another strength. However, the retrospective study design had limitations. Variations in clinical practice may have affected the data collection, particularly the reporting of clinical symptoms. Furthermore, the maternal concentrations were likely to have been trough concentrations, as they were a part of the mothers' clinical follow up, but this was not documented. Lamotrigine concentrations in breast milk have been previously shown to remain relatively stable between doses, making the varying sampling time‐points of the infant concentrations less of a confounder. 26 Finally, it was a limitation that blood tests for haematocrit and thrombocyte profiles were not included in the follow up, since aberrations have previously been reported. 6
5. CONCLUSION
The infant plasma lamotrigine concentrations in this study correlated with the maternal doses and concentrations. While the risk of toxic effects seems to increase with higher maternal doses, infants exposed to lower doses may constitute a low‐risk group, who are eligible for a simplified follow‐up programme. We suggest that the infant's risk of a high plasma lamotrigine concentration and toxic effects might be estimated, based on the maternal dose and, when available, the maternal plasma lamotrigine concentration. Mothers should be advised to reduce breastfeeding when infant lamotrigine levels are within the reference range for epilepsy treatment.
AUTHOR CONTRIBUTIONS
Ingrid Alvarez: Writing – original draft; data curation; formal analysis; funding acquisition; visualization. Katarina Tötterman: Data curation; writing – review and editing; formal analysis. Emma Honkaniemi: Data curation; formal analysis; writing – review and editing. Ihsan Sarman: Conceptualization; writing – review and editing; methodology; data curation. Karin Bäck: Data curation; writing – review and editing; formal analysis. Lisa Forsberg: Conceptualization; methodology; writing – review and editing; funding acquisition; data curation; formal analysis. Essi Whaites Heinonen: Data curation; investigation; funding acquisition; conceptualization; methodology; formal analysis; supervision; project administration; writing – review and editing; visualization. Jenny Svedenkrans: Funding acquisition; conceptualization; methodology; supervision; writing – review and editing; formal analysis; data curation; project administration; visualization; investigation.
FUNDING INFORMATION
This study was funded by the Samaritan Foundation for Paediatric Research, the Mjölkdroppen Foundation (Föreningen Mjölkdroppen), the Solstickan Foundation, the Margarethahemmet Non‐Profit Association, the Anna‐Lisa and Arne Gustafsson Foundation and the HRH Crown Princess Lovisas Society for Paediatric Care. The funders did not take part in any aspect of the study or this paper.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to declare.
ETHICAL APPROVAL
The study was approved by the Swedish Ethical Review Authority on 26 January 2020 (number 2020–05558) and an amendment was approved on 30 December 2021 (number 2021–05866‐02). Written, informed consent was obtained from both parents before the infants were included.
Supporting information
Data S1.
ACKNOWLEDGEMENTS
We are grateful to Dr. Afrodite Psaros Einberg and Dr. Björn Fischler at the Division of Paediatric Gastroenterology, Hepatology and Nutrition at Karolinska University Hospital, for discussions regarding elevated liver transaminases. Our thanks also go to the staff at the Astrid Lindgren's Children's Hospital, the Liljeholmen Outpatient Clinic, Karolinska University Hospital and Sachs' Children and Youth Hospital, Stockholm, Sweden, for initiating and undertaking the clinical follow up of these infants.
Alvarez I, Tötterman K, Honkaniemi E, Sarman I, Bäck K, Forsberg L, et al. Breastfed infants exposed to lamotrigine faced a low risk of toxic effects. Acta Paediatr. 2025;114:346–354. 10.1111/apa.17432
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Supplementary Materials
Data S1.