Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low.

PURPOSE: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. METHOD: Pregnant women with moderate untreated depression were recruited in 2016-2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. RESULTS: Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers', measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. CONCLUSION: Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

Selective serotonin reuptake inhibitor use during pregnancy increases the risk of postpartum hemorrhage and anemia: a hospital-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are known to increase the risk of gastrointestinal bleeding. OBJECTIVE: Study the risk of bleeding-related complications in relation to SSRI in pregnancy. PATIENTS/METHODS: This was a hospital-based cohort study. All women who gave birth at Karolinska University Hospital in Stockholm over a 5-year period (2007 to 2011) were included in the study. Those women who the electronic maternal health record indicated were using SSRI (n = 500) were considered exposed, and all other women formed a control population (n = 39,594). The main outcome measures were blood loss, postpartum hemorrhage (PPH), PP anemia and length of hospitalization. RESULTS: The absolute risk of PPH and PP anemia for the 1.2% exposed to SSRI were 18.0% and 12.8%, respectively. Women with a vaginal non-surgical delivery who reported use of SSRI during pregnancy had approximately a 2-fold increased risk of both PPH (OR, 2.6; 95% CI, 2.0-3.5) and PP anemia (OR, 2.1; 95% CI, 1.5-2.9), as compared with controls. Blood loss and length of hospitalization were significantly higher among women using SSRI than non-users (arithmetic mean 484 mL vs. 398 mL, 3.8 days vs. 2.4 days, respectively). CONCLUSION: The use of SSRI during pregnancy increases blood loss and doubles the risk of PPH and PP anemia in a setting where SSRI had not been considered a risk factor for increased blood loss. Because PPH is a leading cause of maternal mortality and morbidity, the awareness of bleeding-related complications is important, both in relation to pregnancy and to surgery in general.

Pregnancy and lactation in a woman with classical galactosaemia heterozygous for p.Q188R and p.R333W.

A 31-year old patient who is compound heterozygous for the two galactose-1-phosphate uridyltransferase mutations p.Q188R and p.R333W delivered two healthy boys after uneventful spontaneous pregnancies. The patient chose to breast-feed her first baby and her galactose metabolites in blood and urine were monitored closely. A temporary increase in her galactose-1-phosphate (gal-1-P) levels with a maximum of 0.30 mmol/L on day 2 after delivery was observed. Galactose-1-phosphate was normalized 10 days after delivery. At the time of weaning, 8 months after delivery, her menses returned and she had normal sex steroid levels. She became pregnant again 2 months later. The second baby was also breast-fed. This time an increase in her gal-1-P values could be seen for 3 weeks with a maximum gal-1-P level of of 0.25 mmol/L at day 7. Only minor changes in her urine galactitol values were noted during the study period but the values stayed in the range of treated galactosaemia patients. We thus report that breast-feeding has been possible with only small adverse effects on the levels of galactose metabolites in a patient with classical galactosaemia.

Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia.

BACKGROUND: The role of nitric oxide (NO) in normal pregnancy and pregnancy complicated with preeclampsia (PE) and/or intrauterine growth restriction (IUGR) still remains questionable. The placenta lacks autonomic innervation, therefore blood flow must be regulated by humoral and endothelium derived factors. NO is a potent vasodilator released by endothelial cells. It is synthesized by the catalytic action of the endothelial constitutive nitric oxide synthase (ecNOS). Moreover, the synthesis of NO in normal human placental vasculature has already been established and impairment of the uteroplacental blood flow in pregnancies complicated by PE and/or IUGR has been demonstrated. DESIGN AND METHODS: The aim of the present study was to compare the expression of ecNOS mRNA in placenta from women with complicated and normal pregnancies. Placenta was collected from women with PE (n = 13) or small for gestational age (SGA) (n = 8), both PE and SGA (n = 7) and normal pregnancies (n = 41). Total nucleic acids were prepared and a solution hybridization technique was used for mRNA analysis. RESULT: The mRNA expression of ecNOS was significantly higher (p<0.05) in all groups of complicated pregnancies compared to normal pregnancies. CONCLUSION: Our findings indicate that the increased placental expression of ecNOS mRNA might reflect a compensatory mechanism in the disturbed uterine circulation seen in PE and/or SGA.

Altered mRNA expression pattern of placental epidermal growth factor receptor (EGFR) in pregnancies complicated by preeclampsia and/or intrauterine growth retardation.

Placental pathology in preeclampsia (PE) and intrauterine growth retardation (IUGR) is associated with alterations of the placental epidermal growth factor receptor (EGFR). It is encoded by a single gene, which gives rise to two different full-length transcripts and one putative truncated transcript in the placenta. The aim was to investigate if the placental mRNA expression pattern of EGFR differs between women with PE and/or IUGR and normal pregnancies. Tissue samples from placentas were obtained immediately after delivery. Total nucleic acids were prepared and mRNA levels of EGFR transcripts were measured by a solution hybridization technique. In the group with IUGR the placental mRNA expression of the two full-length transcripts was found to be significantly lower than in placentas from normal pregnancy, whereas the expression of the truncated transcript was higher. The groups with PE or PE with IUGR had a significantly higher mRNA expression of the truncated transcript, while there were no significant differences in the mRNA expression of the two full-length transcripts. These findings are consistent with an important role for EGFR in the regulation of placental and fetal growth.

Differences in mRNA expression of endothelin-1, c-fos and c-jun in placentas from normal pregnancies and pregnancies complicated with preeclampsia and/or intrauterine growth retardation.

A defect in placental function has been suggested to be associated both with preeclampsia (PE), with or without concomitant intrauterine growth retardation (IUGR), and with IUGR as a single entity. Our aim was to compare the mRNA expression of the growth-related protooncogenes c-fos and c-jun and the vasoconstrictor and growth factor endothelin-1 (ET-1) in placentas from normal pregnancies with those of PE and IUGR. The mRNA expression of c-jun was significantly higher in all groups of complicated pregnancies while ET-1 and c-fos mRNA expression was significantly higher only in the group with IUGR. These results support the concept that an aberrant placental mRNA expression of the ET-1, c-fos and c-jun genes is part of an altered pattern of gene expression in pathological pregnancies.