High lithium concentration at delivery is a potential risk factor for adverse outcomes in breastfed infants: a retrospective cohort study.

BACKGROUND: Neonatal effects of late intrauterine and early postpartum exposure to lithium through mother's own milk are scarcely studied. It is unclear whether described symptoms in breastfed neonates are caused by placental lithium transfer or postnatal exposure to lithium through breastfeeding. We aimed to investigate lithium clearance and neonatal morbidity in breastfed infants with high versus low serum lithium concentrations at birth. METHODS: This retrospective study focused on breastfed infants to women treated with lithium during and after pregnancy, born between 2006 and 2021 in Stockholm, Sweden. Information on serum lithium concentrations and adverse neonatal outcomes was obtained from medical records. Neonatal symptoms and lithium clearance were compared between a high exposure group (HEG, lithium concentrations ≥ 0.6 meq/l) and a low exposure group (LEG, < 0.6 meq/l). RESULTS: A total of 25 infant-mother dyads were included. Median lithium serum concentration at birth was 0.90 meq/l in the HEG as compared with 0.40 meq/l in the LEG (p < 0.05). The difference was still significant at follow-up (0.20 meq/l vs 0.06 meq/l, p < 0.05), despite reduction in maternal dose. The rate of neonatal symptoms was 85.7% in HEG and 41.2% in LEG (p = 0.08) at birth and 28.6% vs 11.8% at follow-up (p = 0.55). Furthermore, 28.6% of infants in HEG were admitted to neonatal care, vs 5.9% in LEG (p = 0.19). Two infants in the HEG had therapeutic lithium levels at follow-up. All infants with symptoms at follow-up were either in the HEG or exposed to additional psychotropic medication. CONCLUSIONS: Neonatal symptoms are common after late intrauterine lithium exposure, however transient, treatable and mostly mild. In this study, a high lithium concentration at birth was a risk factor for an increased lithium level at follow-up. Polypharmacy may constitute an additional risk factor. This study suggests that the late intrauterine exposure to lithium might add to the adverse effects in lithium-exposed, breastfed infants. Consequently we recommend breastfed infants with therapeutic lithium concentrations at birth to be followed up promptly to avoid lithium toxicity.

Lithium use during breastfeeding was safe in healthy full-term infants under strict monitoring.

AIM: Previous studies on breastfeeding during lithium therapy have shown conflicting results. The aim of this study was to evaluate the safety when practising thorough follow-up of the infants. METHOD: This retrospective study focused on women with lithium medication, and their breastfed infants born between 2006 and 2021 in Stockholm, Sweden. Information about infant serum lithium concentrations and clinical status was collected from medical records. RESULTS: In total, 30 infants exposed to lithium through breastmilk, 21 girls and 9 boys, were included. The median age at follow-up was 40 days (range 8-364 days). The median lithium serum concentration was 0.10 mmol/L in the second week of life (range <0.05-0.7 mmol/L), 0.08 in week 2-4 (range <0.05-1.2), 0.06 in the second month of life (range <0.05-0.2) and 0.07 after 2 months of age (range <0.05-0.2). Unexpectedly high lithium concentrations were found in two infants in the first month of life. Apart from poor weight gain, no adverse effects were found. CONCLUSION: Serum lithium concentrations in breastfed infants were stabilised at barely measurable levels after the first weeks of life. Before that, concentrations higher than the mothers were found. Lithium treatment during breastfeeding can be considered safe under strict follow-up.

Review shows that early foetal alcohol exposure may cause adverse effects even when the mother consumes low levels.

AIM: Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. METHODS: Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases. We also report the findings of a human study using three-dimensional photography of the face to explore associations between PAE and craniofacial phenotyping. RESULTS: Animal models with different alcohol exposure patterns show that early PAE may lead to long-term chronic effects, due to developmental programming for some adult diseases in cardiovascular, metabolic and renal systems. The study with three-dimensional photographing is very promising in helping paediatricians to understand how even small amounts of PAE can affect craniofacial phenotyping. CONCLUSION: Even low levels of PAE can cause adverse foetal effects and not just in the brain. It is not currently possible to determine a safe period and level when alcohol consumption would not affect the foetus.

[Fetal alcohol syndrome is not the only consequence of prenatal alcohol exposure]. / Alkohol under graviditet kan riskera folkhälsan - Alkohol under fosterlivet påverkar inte bara barnets hjärna ­ risk för kardiovaskulära och metabola sjukdomar på sikt.

Fetal alcohol syndrome is not the only consequence of prenatal alcohol exposure  The prevalence of fetal alcohol syndrome and fetal alcohol spectrum disorders in larger communities in USA is now updated to 0.4 % and 4.8 % respectively. Affected individuals bear witness to disease symptoms from many organ systems in addition to the brain and behavioural dysfunctions. In the light of modern epigenetic research, early alcohol exposure appears to play a hidden role in fetal reprogramming. The underlying mechanisms explain the ¼developmental origin of health and disease«, which has an impact on complex interactions between genome, environment and epigenetics.

Hospital-assisted home care after early discharge from a Swedish neonatal intensive care unit was safe and readmissions were rare.

AIM: It is common in Sweden to discharge infants early from a neonatal intensive care unit (NICU) and provide hospital-assisted neonatal home care (HANHC), as an alternative to hospital care, for infants with a persisting need for specialised care. This study assessed the safety of HANHC by reviewing hospital readmissions. METHODS: We retrospectively reviewed the files of all 1410 infants enrolled in HANHC at the NICU at Sachs' Children's Hospital, Stockholm, from 2002 to 2011 up until hospital readmission or their discharge from HANHC. Each readmitted infant was matched to the next HANHC infant who was not readmitted. Predictors and reasons for readmission were investigated in a retrospective nested case-control study. RESULTS: We readmitted 74 (5.2%) of the 1410 infants in HANHC. Extremely preterm infants, born at less than 28 weeks, were readmitted more frequently than other infants, with an odds ratio of 6.07 (range 2.06-17.8). The most common symptoms were respiratory symptoms (55%), and viral respiratory tract infections were the most common reason (28%) for readmission. CONCLUSION: HANHC was safe for the vast majority of infants (94.8%). Extremely preterm birth was identified as a predictor for hospital readmission. Further studies investigating the safety of HANHC in other settings would be valuable.

Narcolepsy Treated with Racemic Amphetamine during Pregnancy and Breastfeeding.

This case report describes a woman with narcolepsy treated with racemic amphetamine (rac-amphetamine) during pregnancy and breastfeeding with follow-up on the infant's development up to 10 months of age. The pregnancy outcome and the pharmacokinetics of rac-amphetamine were studied during breastfeeding. The pregnancy and the delivery were uneventful. Concentrations of rac-amphetamine were determined in the plasma of the mother and infant, and in the breast milk with a liquid chromatography-mass spectrometry method. Samples were obtained at 2, 5, and 9 weeks postpartum. The transfer of rac-amphetamine to the breast milk was extensive (mean milk/maternal plasma concentration ratio approximately 3). The breastfed infant had a low plasma concentration of rac-amphetamine (about 9% of the maternal plasma level) and the calculated relative infant dose was low (2%). No adverse effects were observed in the breastfed infant. The infant's somatic and psychomotor development up to 10 months of age was normal. Further studies of amphetamine prescribed for medical reasons during pregnancy and lactation are needed.

Neurobehavioural development of preschool-age children born to addicted mothers given opiate maintenance treatment with buprenorphine during pregnancy.

AIM: To study the neurobehavioural development and somatic growth of children at preschool-age born to opioid-addicted mothers given opiate maintenance treatment (OMT) with buprenorphine during pregnancy. METHODS: Twenty-eight children, whose 21 opiate-addicted mothers were treated with OMT during pregnancy and accepted participation to the study, went through a battery of neurobehavioural tests (WPPSI-R, McCarthy, BROWN and SDQ). Twenty-five children fulfilled the tests at an age of 5-6 years. RESULTS: The children showed evidence of serious visual motor and attention problems in the field of performance (WPPSI-R scales) and major problems in the field of motor skills and memory abilities (McCarthy Scales). The results of behavioural tests also showed significantly elevated levels of hyperactivity, impulsivity and attention problems on the attention deficit hyperactivity disorder (ADHD) scale in BROWN and in SDQ tests estimated by the teachers, while the parents estimated no problems for their children. Regarding the outcomes, there were no significant differences in terms of neonatal abstinence syndrome, gender or socio-economic factors. The somatic growth of the children corresponded to the mean values of the normal population in weight, length and head circumference at birth and at preschool-age, respectively. CONCLUSION: Children to opiate-addicted mothers with buprenorphine maintenance treatment during pregnancy constitute a risk population, which should be recognized before start of the school. Whether the effects are associated with buprenorphine exposition during foetal life or not are discussed and need further investigation.

The Stockholm Neonatal Family-Centered Care Study: effects on salivary cortisol in infants and their mothers.

BACKGROUND: Parental involvement in the care of preterm infants in neonatal intensive care units (NICUs) is common, but little is known about the effect on stress responses in mothers and infants. AIMS: The aim of this study is to evaluate the effect of family-centered care on salivary cortisol reactivity in mothers and preterm infants and the correlation between the mothers' and the preterm infants' salivary cortisol levels. METHODS: This study is part of a randomized controlled trial conducted at two level-II NICUs, including Family Care (FC), where parents were able to stay 24h/day from admission to discharge, and Standard Care (SC). To investigate the cortisol response, saliva was collected from 289 preterm infants and their mothers before and after a diaper change at the time of discharge. RESULTS: No significant differences were found between the two groups in salivary cortisol reactivity, either in mothers or in infants. The results revealed a correlation between preterm infants' and their mothers' baseline and response cortisol in the FC group: r=0.31 (p=0.001) and r=0.24 (p=0.01), respectively. Such correlation was not observed in the SC group: r=0.14 (p=0.14) and r=0.18 (p=0.07), respectively. CONCLUSIONS: Family-centered care had no effect on salivary cortisol reactivity during diaper change. However, sharing the same environment may increase the concordance between preterm infants' and their mothers' salivary cortisol levels.

The Stockholm Neonatal Family Centered Care Study: effects on length of stay and infant morbidity.

OBJECTIVE: Parental involvement in the care of preterm infants in NICUs is becoming increasingly common, but little is known about its effect on infants' length of hospital stay and infant morbidity. Our goal was to evaluate the effect of a new model of family care (FC) in a level 2 NICU, where parents could stay 24 hours/day from admission to discharge. METHODS: A randomized, controlled trial was conducted in 2 NICUs (both level 2), including a standard care (SC) ward and an FC ward, where parents could stay from infant admission to discharge. In total, 366 infants born before 37$$\raisebox{1ex}{$0$}\!\left/ \!\raisebox{-1ex}{$7$}\right.$$ weeks of gestation were randomly assigned to FC or SC on admission. The primary outcome was total length of hospital stay, and the secondary outcome was short-term infant morbidity. The analyses were adjusted for maternal ethnic background, gestational age, and hospital site. RESULTS: Total length of hospital stay was reduced by 5.3 days: from a mean of 32.8 days (95% confidence interval [CI]: 29.6-35.9) in SC to 27.4 days (95% CI: 23.2-31.7) in FC (P = .05). This difference was mainly related to the period of intensive care. No statistical differences were observed in infant morbidity, except for a reduced risk of moderate-to-severe bronchopulmonary dysplasia: 1.6% in the FC group compared with 6.0% in the SC group (adjusted odds ratio: 0.18 [95% CI: 0.04-0.8]). CONCLUSIONS: Providing facilities for parents to stay in the neonatal unit from admission to discharge may reduce the total length of stay for infants born prematurely. The reduced risk of moderate-to-severe bronchopulmonary dysplasia needs additional investigation.

Transfer of buprenorphine into breast milk and calculation of infant drug dose.

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.

Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series.

AIM: To compare the effects of fetal buprenorphine and methadone exposure during maintenance treatment of pregnant heroin dependent subjects. DESIGN AND SETTING: A population based comparison of consecutive, prospectively followed buprenorphine-exposed pregnancies in Stockholm County, Sweden, to retrospectively analyzed consecutive methadone-exposed pregnancies. PARTICIPANTS: All 47 pregnancies in 39 women with opiate dependence and buprenorphine maintenance treatment 2001-2006, and all 35 methadone-exposed pregnancies (26 women) 1982-2006 in Stockholm County. MEASUREMENTS: Intrauterine growth, birth outcome, malformations, neonatal adaptation, withdrawal syndrome and infant mortality. FINDINGS: Buprenorphine-exposed pregnancies resulted in 47 uneventful live births (2 twin pairs), 1 stillbirth (for which no explanation was found) and 1 miscarriage. The birth weight of the infants was normal. Neonatal abstinence syndrome (NAS) occurred in 19 cases (40.4%), the majority mild in nature and only 7 (14.9%) needing withdrawal treatment. Compared to 35 infants born after intrauterine methadone exposure at the same hospital since 1982 (77.8% of them exhibiting NAS and 52.8% needing withdrawal treatment), there were significant advantages with buprenorphine treatment: birth weight was higher, due to longer gestation. Incidence of NAS of any intensity, as well as incidence of NAS that required pharmacological treatment was lower, while length of hospital stay was shorter. When buprenorphine treatment started pre-conception, NAS at any level was significantly less frequent than in subjects with post-conception initiated treatment (7/27, 26%; 12/20, 60%, respectively). CONCLUSIONS: Data from this non-randomized comparison suggest that buprenorphine may offer advantages for treatment of opiate dependence during pregnancy.