Comprehensive measurements of intrauterine and postnatal exposure to lamotrigine

The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug. Concentrations of lamotrigine were measured in 19 mother-infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. A no-intercept model was applied for associations between maternal serum concentrations, amniotic fluid, umbilical cord blood, and breast milk concentrations. The mean daily dosage of lamotrigine was 351.32mg (range 50-650mg). We detected associations between maternal serum and amniotic fluid (β=0.088, p<0.001), as well as umbilical cord (β=0.939, p<0.001) and breast milk (β=0.964, p<0.001). The median penetration ratio into amniotic fluid, cord blood, and breast milk was 0.68, 0.92, and 0.77, respectively. Lamotrigine concentrations in amniotic fluid, cord blood, and breast milk give evidence that the fetus/newborn is constantly exposed to lamotrigine. Maternal serum concentrations predicted exposure via amniotic fluid, umbilical cord, and breast milk. Data suggest that therapeutic drug monitoring can be recommended as part of the clinical routine in psychopharmacotherapy for pregnant or breastfeeding women.

Pregnancy exposure to venlafaxine—Therapeutic drug monitoring in maternal blood, amniotic fluid and umbilical cord blood and obstetrical outcomes

This study is the first to measure and correlate lamotrigine concentrations in maternal blood, amniotic fluid, and umbilical cord blood and account for distribution of the drug between these three compartments. Concentrations of lamotrigine were measured in six mother-infant pairs at the time of delivery. Daily doses of lamotrigine ranged between 200 and 650 mg. Daily doses were correlated with maternal serum and umbilical cord blood concentrations, and serum levels were correlated with levels in amniotic fluid. Lamotrigine levels in serum correlated strongly with the lamotrigine levels in amniotic fluid (r=+0.986, P<0.001) and cord blood (r=+0.928, P=0.008). The penetration ratio into amniotic fluid was in a range between 0.31 and 0.75 (mean 0.58, SD 0.17); the penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood levels, was found to be in a range between 0.48 and 1.27 (mean 0.81, SD 0.28). Lamotrigine concentrations in amniotic fluid provided evidence that maternally administered lamotrigine is accessible to the fetus in a manner not previously appreciated. Furthermore, the penetration ratio into umbilical cord blood calculated here is in line with the largest study carried out so far to explore transplacental transfer.

Pregnancy exposure to citalopram – Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood

Sertraline in pregnancy – Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood

Pregnancy exposure to quetiapine – Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood and obstetrical outcomes

Introduction: Treatment of psychiatric diseases during pregnancy is complicated by the concern for the safety of the unborn child because all psychotropic medications more or less cross the placenta. Fetal outcome is influenced by various factors and – among others – the effects of a specific drug itself depend on the concentration in maternal and fetal serum as well as on its concentration in amniotic fluid. Method: The present study is a naturalistic prospective investigation of different psychotropic drug concentrations in maternal serum (MS) and amniotic fluid (AF) of 14 women and umbilical cord blood (UC) of nine newborns. The women were treated with different doses of psychotropic drugs such as antidepressants, antipsychotics, anticonvulsants and others. Results: Patients received thirteen different psychotropic drugs. Results are available for five antidepressants (citalopram, paroxetine, sertraline, fluoxetine and venlafaxine), 3 anticonvulsants (valproic acid, levetiracetam, lamotrigine), 2 benzodiazepines (diazepam, clobazam), as well as for olanzapine, methadone and methylphenidate. Concentrations of different psychotropic drugs were found in maternal plasma, amniotic fluid an umbilical cord blood in highly variable concentrations suggesting that fetal exposure is continual and may occur through a variety of paths accounting for increased fetal exposure. Conclusion: The preliminary data of this ongoing study highlight the penetration of different psychotropic drugs into the amniotic fluid as another way of fetal exposure. Of particular interest in this context is the observation that the well known teratogenic valproic acid does not accumulate in AF in approximately the same way as other anticonvulsants do, however valproic acid has the highest penetration ratio into umbilical cord blood with potentially negative effects on the offspring. Understanding the current data and their limitations will allow providers to guide their patients in choosing treatment options. Consistent and simple strategies should be used when discussing the risk-benefit analysis with the patient.

The association between elevated interleukin (IL)-8 concentrations in amniotic fluid and preterm delivery is well described. Little consideration has been given to the impact of different groups of microorganisms within the amniotic cavity on IL-8 concentration. We collected amniotic fluid, placental tissue and amniotic membranes during preterm cesarean sections for bacterial culture. In addition, we determined IL-8 concentrations in maternal serum, amniotic fluid and cord blood and correlated them with the various intra-amniotic pathogens isolated by bacterial culture. IL-8 concentrations were determined in amniotic fluid in 107 cases, in cord blood in 185 cases and in maternal blood in 158 cases. Women with intra-amniotic Ureaplasma urealyticum infection had significantly higher amniotic fluid concentrations of IL-8 than those without (P< 0.001). In cord blood, we found significantly elevated IL-8 concentrations due to intra-amniotic infection with U. urealyticum (P=0.045) and other pathogens (P=0.04). In maternal sera, we found no significant elevation of maternal IL-8 in any of the groups. Intrauterine infection with U. urealyticum seems to play a profound role in the cascade of inflammation and increases IL-8 concentrations in amniotic fluid and cord blood.

IntroductionFolate is required for fetal, placental and maternal tissue growth during pregnancy. A decline in maternal circulating folate concentrations and an increase in total homocysteine (a non-specific indicator of folate deficiency) have been observed with the progression of pregnancy. However, the role of folate in the third trimester of pregnancy is not clear and folate status in late pregnancy has not so far been widely analyzed. The main aim of this retrospective cross-sectional study was to determine the folate concentrations in amniotic fluid and in maternal and umbilical cord blood serum derived during delivery.Material and methodsThis study was conducted on 175 pregnant Polish women (white/Caucasian) aged between 17 and 42 years. Only pregnancies without birth defects were included in this study. Amniotic fluid, maternal serum, and umbilical cord blood samples were collected during vaginal delivery or cesarean section. Folate concentration was determined using a microbiological assay.ResultsStrong correlations were observed between the concentrations of folate in amniotic fluid and maternal serum (rho = 0.67, p < 0.001) and amniotic fluid and cord blood serum (rho = 0.49, p < 0.001) and between maternal serum and cord blood serum (rho = 0.67, p < 0.001). Folate concentrations in amniotic fluid were significantly associated with maternal age (rho = 0.19, p < 0.05). Pre-pregnancy body mass index and maternal weight/neonatal birth weight ratio were independent predictors of folate concentrations in maternal serum (β = 0.33, p < 0.05; β = –0.19, p < 0.05) and amniotic fluid (β = 0.28, p < 0.05; β = –0.19, p < 0.05) in late pregnancy.ConclusionsFolate concentrations in amniotic fluid are associated with maternal and neonatal folate status peripartum in healthy women.

Lead and cadmium concentrations in maternal and umbilical cord blood, amniotic fluid, placenta, and amniotic membranes

Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk.

ObjectiveData on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium. MethodsWe conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size. ResultsNinety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27–5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02–1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11–4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52–0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5–7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01–0.22, n = 121). DiscussionWe observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.

Antidepressant transfer into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis

The presence of the adipokines adiponectin and leptin in cord blood and placental and fetal tissues suggests a possible role in fetal development. We measured concentrations of adiponectin and leptin in maternal serum, cord blood, and breast milk and examined their correlations within a large, population-based study. Between November 2000 and November 2001, we recruited all mothers and their newborns after delivery at the University of Ulm (Ulm, Germany). The current analysis included 766 mothers with available breast milk samples collected 6 weeks postpartum. Adipokine concentrations were measured with commercially available ELISAs (R&D Systems). Median adiponectin concentrations in maternal serum (n=713), cord blood (n=709), and breast milk (n=766) were 8.6 mg/L, 30.6 mg/L, and 10.9 microg/L, respectively. Median leptin concentrations were 12.8 microg/L in maternal serum, 7.8 microg/L in cord blood, and 174.5 ng/L in breast milk. Whereas increases in leptin concentrations with increasing birth weight, birth weight according to gestational age, and ponderal index were statistically significant in cord blood (all P values<0.0001), cord blood adiponectin was clearly related only to birth weight (P=0.0004). Concentrations of both adipokines were moderately correlated in breast milk and maternal serum (both Spearman rho values were 0.43; P<0.0001). Concentrations of adiponectin and leptin vary strongly in maternal serum, cord blood, and breast milk, with only moderate correlations between both adipokines in maternal serum and breast milk. The health implications of these patterns warrant further investigation.

S100B protein is a unique calcium-binding protein. Its biological role within the cell populations is not completely defined. Some pathological conditions that develop during pregnancy could affect S100B concentrations in the amniotic fluid, cord blood, and maternal serum. The aim of our study was to assess the correlation between S100B protein expression in the amnion, amniotic fluid and gestational age in the third trimester of uncomplicated pregnancies. Amnion, amniotic fluid, maternal peripheral and umbilical cord blood samples were collected from healthy women who delivered at 31-36 weeks (n=17), 37-40 weeks (n=22), and 41-42 weeks (n=21). The expression of S100B in the amnion was assessed by immunohistochemistry and real-time (RT)-PCR, and its concentrations in amniotic fluid, maternal and cord blood sera were determined by ELISA. The S100B protein expression in the amnion and its concentrations in amniotic fluid, maternal and cord blood sera of patients in the third trimester were not significantly different at various gestational ages. The S100B protein expression in the amnion and the S100B protein concentrations in amniotic fluid, maternal and cord blood do not vary significantly in the third trimester of uncomplicated pregnancies.