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.

Neonatal morbidity after fetal exposure to antipsychotics: a national register-based study.

OBJECTIVE: To investigate the admission rate to neonatal care and neonatal morbidity after maternal use of antipsychotics during pregnancy. DESIGN: A population-based register study. SETTING: Information on all singleton births between July 2006 and December 2017 in Sweden including data on prescription drugs, deliveries and infants' health was obtained from the Swedish Medical Birth Register, the Prescribed Drug Register and the Swedish Neonatal Quality Register. Exposed infants were compared with unexposed infants and with infants to mothers treated with antipsychotics before or after but not during pregnancy. PARTICIPANTS: The cohort comprised a total of 1 307 487 infants, of whom 2677 (0.2%) were exposed to antipsychotics during pregnancy and 34 492 (2.6%) had mothers who were treated before/after the pregnancy. OUTCOME MEASURES: The primary outcome was admission rate to neonatal care. Secondary outcomes were the separate neonatal morbidities. RESULTS: Of the exposed infants, 516 (19.3%) were admitted to neonatal care compared with 98 976 (7.8%) of the unexposed infants (adjusted risk ratio (aRR): 1.7; 95% CI: 1.6 to 1.8), with a further increased risk after exposure in late pregnancy. The highest relative risks were seen for withdrawal symptoms (aRR: 17.7; 95% CI: 9.6 to 32.6), neurological disorders (aRR: 3.4; 95% CI: 2.4 to 5.7) and persistent pulmonary hypertension (aRR: 2.1; 95% CI: 1.4 to 3.1) when compared with unexposed infants. The absolute risks for these outcomes were however low among the exposed infants, 1.3%, 1.8% and 1.0%, respectively, and the relative risks were lower when compared with infants to mothers treated before/after the pregnancy. CONCLUSION: Fetal exposure to antipsychotics was associated with an increased risk of neonatal morbidity. The effects in the exposed infants seem transient and predominantly mild, and these findings do not warrant discontinuation of a necessary treatment but rather increased monitoring of these infants. The increased risk of persistent pulmonary hypertension requires further studies.

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.

Antipsychotic Use During Pregnancy and Risk for Gestational Diabetes: A National Register-Based Cohort Study in Sweden.

OBJECTIVE: We aimed to study whether antipsychotic use during pregnancy is associated with gestational diabetes. METHODS: This was a Swedish national register-based cohort study on the Medical Birth Register and the Prescribed Drug Register including all 1,307,487 singleton births between July 2006 and December 2017. Antipsychotics were divided into first-generation antipsychotics (n = 728), high-risk metabolic second-generation antipsychotics including olanzapine, clozapine and quetiapine (n = 1710), and other second-generation antipsychotics (n = 541). The risks for gestational diabetes, foetal growth disturbances, pre-eclampsia, caesarean section and preterm labour were assessed. Women treated during pregnancy were compared to women not treated during pregnancy and to women who used antipsychotics before/after but not during pregnancy. RESULTS: The crude risk ratio for gestational diabetes for women treated with high-risk metabolic second-generation antipsychotics during pregnancy was 2.2 (95% confidence interval [CI] 1.6-2.9) compared to untreated pregnant women (n = 1,296,539) and 1.8 (95% CI 1.4-2.5) compared to women treated before/after pregnancy (n = 34,492). After adjustment for maternal factors including body mass index, the risk ratios were 1.8 (95% CI 1.3-2.4) and 1.6 (95% CI 1.2-2.1). Exposed infants had an increased risk of being large for gestational age: adjusted risk ratios 1.6 (95% CI 1.3-1.9) and 1.3 (95% CI 1.1-1.6) compared to no maternal antipsychotic use during pregnancy and maternal use before/after the pregnancy. Other antipsychotics were not associated with metabolic risks. CONCLUSIONS: Olanzapine, clozapine and quetiapine used during pregnancy were associated with increased risks for gestational diabetes and the infant being large for gestational age. Enhanced metabolic monitoring should be considered for pregnant women using these drugs.

The use of second-generation antipsychotics amongst pregnant women is increasing. The side effects of these drugs, for example weight gain and increased blood sugar, are well described for the general population. In particular, olanzapine, quetiapine and clozapine are known to cause these effects. Studies on their effects on blood sugar control in pregnant women have however been conflicting. Pregnancy itself also imposes a risk for increased blood sugar levels and gestational diabetes. The purpose of this study was to evaluate the risk of gestational diabetes connected to the use of antipsychotics during pregnancy. The study was nationwide and register based including 1.3 million births in Sweden between July 2006 and December 2017. The rates of gestational diabetes and the infants being small for gestational age or large for gestational age amongst women treated with antipsychotics were compared to the rates in pregnant women who did not receive antipsychotics and to rates in a control group of women treated with antipsychotics before/after but not during pregnancy. Antipsychotics were divided into three groups: (i) first-generation antipsychotics, (ii) high-risk second-generation antipsychotics including olanzapine, quetiapine and clozapine, and (iii) other second-generation antipsychotics. Women treated with high-risk second-generation antipsychotics were found to have an increased risk of gestational diabetes and giving birth to an infant being large for gestational age, both when compared with untreated pregnant women and with the control group. Other antipsychotics were not connected to increased risks of these outcomes. Hence, pregnant women treated with olanzapine, quetiapine or clozapine should be monitored regarding blood sugar levels.

MAGDALENA: study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero.

INTRODUCTION: Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy. METHODS AND ANALYSIS: MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups. ETHICS AND DISSEMINATION: This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public. TRIAL REGISTRATION NUMBER: EudraCT2013-004444-31; Pre-results.

Lactate clearance predicts outcome after major trauma

Introduction:To determine a correlation between lactate clearance within 48h and survival in trauma patients at a Level I trauma centre in a developing country and compare to previous international lactate clearance studies.Methods:We conducted a retrospective study of a prospectively collected database at a Level I trauma centre from March 2007 to November 2010. Patients of all ages were included. Metabolic parameters from initial arterial blood gas were measured in all patients; an abnormal lactate beindefined as 2.5mmol/L. A subgroup analysis of blunt versus penetrating injury was performed. Results:Of the 657 patients in the database; 493 had complete lactate data. The survival rate of patients with lactate values 2.5mmol/L was 88. Of the patients with high lactate levels that cleared within 24 and 48h the survival rates were 81 and 71; respectively. The survival rate amongst patients not achieving a normal lactate within 48h was 46 but was higher in those with penetrating as opposed to blunt injury (67 versus 38). The overall survival was 81.Conclusion:The present results confirm previous studies showing that prolonged lactate clearance predicts increased mortality in severely injured trauma patients. Thus; the measurements of arterial serum lactate trends are simple and effective predictors of outcome