Placental passage of antidepressant medications

OBJECTIVE: This study determined the placental transfer of antidepressants and their metabolites. METHOD: A total of 38 pregnant women taking citalopram, fluoxetine, paroxetine, or sertraline participated. Maternal and umbilical cord blood samples were obtained to determine antidepressant and metabolite concentrations. RESULTS: Antidepressant and metabolite concentrations were detectable in 86.8% of umbilical cord samples. The mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89. The lowest ratios were for sertraline and paroxetine; the highest were for citalopram and fluoxetine. Maternal doses of sertraline and fluoxetine correlated with umbilical cord concentrations of these medications. CONCLUSIONS: Umbilical cord concentrations of antidepressants and their metabolites were almost invariably lower than corresponding maternal concentrations. Maternal doses predicted umbilical concentrations of fluoxetine and sertraline. Mean umbilical cord to maternal serum ratios were significantly lower for sertraline than fluoxetine, suggesting that sertraline may produce less fetal medication exposure than fluoxetine near delivery.     

Placental passage of tricyclic antidepressants.

BACKGROUND: The use of antidepressants during pregnancy continues to garner considerable attention, though there are limited investigations that have sought to quantify fetal exposure. METHODS: Maternal and umbilical cord sera were collected at delivery from ten women taking nortriptyline and seven taking clomipramine. Placental passage was calculated as the ratio of umbilical cord to maternal serum concentration. Obstetrical outcome data were gathered from subjects at delivery. RESULTS: The placental passage ratio of nortriptyline and its active metabolite, cis-10-hydroxynortriptyline, were .68 +/- .40, 1.40 +/- 2.40, respectively. Clomipramine and desmethylclomipramine ratios were .60 +/- .50, .80 +/- .60. Obstetrical complications, such as pre-term delivery and pregnancy induced hypertension, were increased compared to the national average. CONCLUSIONS: The in vivo ratios of umbilical cord to maternal serum drug concentrations demonstrate considerable fetal exposure and differ greatly from previous results utilizing ex vivo perfusion.     

Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes

OBJECTIVES: There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery. METHOD: The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng/ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records. RESULTS: Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine. CONCLUSIONS: All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.     

Antidepressants in amniotic fluid: another route of fetal exposure

OBJECTIVE: The authors' goal was to determine the concentration of antidepressants in amniotic fluid during maternal treatment of depression. METHOD: Women treated with antidepressants undergoing amniocentesis for obstetrical reasons were enrolled. Antidepressant concentrations in amniotic fluid and maternal serum were determined with high-performance liquid chromatography. RESULTS: Amniotic fluid was obtained from 27 women, and the amniotic fluid's antidepressant concentrations were highly variable. For the parent compounds, the amniotic fluid concentrations of selective serotonin uptake inhibitors averaged 11.6% (SD=9.9%) of maternal serum concentrations (N=22). Amniotic fluid to maternal serum ratios were higher for venlafaxine: 172% (SD=91%) (N=3). Of interest, the amniotic fluid to maternal serum ratios for the metabolites (N=19) did not demonstrate a consistent pattern compared to the parent compound ratios. In 10 subjects, the amniotic fluid to maternal serum ratio for the metabolites was higher than the parent compound and lower in the remaining nine subjects. CONCLUSIONS: The pattern of antidepressant concentrations in amniotic fluid is similar to recent data for placental passage. Although the significance of amniotic fluid exposure remains to be determined, these results demonstrate that maternally administered antidepressants are accessible to the fetus in a manner not previously appreciated.     

Placental passage of antiepileptic drugs at delivery and neonatal outcomes

Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical‐to‐maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother–newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical‐to‐maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical‐to‐maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical‐to‐maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications.     

Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy

OBJECTIVE: Lithium has been used during pregnancy for more than four decades, but quantification of fetal lithium exposure and clinical correlations of such exposure are limited. The study objectives were to 1) quantify the rate of lithium placental passage, 2) assess any association between plasma concentration of lithium at delivery and adverse perinatal events, and 3) determine whether lithium concentrations can be reduced by briefly suspending therapy proximate to delivery. METHOD: Maternal blood and umbilical cord blood were obtained at delivery for assay of lithium concentrations, and obstetrical outcome data were collected prospectively for 10 participants. These data were combined with results from MEDLINE and PsycINFO searches that identified 32 cases in which maternal lithium was administered throughout delivery. Statistical analysis of the pooled data was conducted. RESULTS: The ratio of lithium concentrations in umbilical cord blood to maternal blood (mean=1.05, SD=0.13) was uniform across a wide range of maternal concentrations (0.2-2.6 meq/liter). Significantly lower Apgar scores, longer hospital stays, and higher rates of CNS and neuromuscular complications were observed in infants with higher lithium concentrations (>0.64 meq/liter) at delivery. Withholding lithium therapy for 24-48 hours before delivery resulted in a 0.28 meq/liter reduction in maternal lithium concentration. CONCLUSIONS: Lithium completely equilibrates across the placenta. Higher lithium concentrations at delivery are associated with more perinatal complications, and lithium concentrations can be reduced by brief suspension of therapy proximate to delivery. Treatment guidelines are proposed to improve neonatal well-being when lithium use is indicated in late pregnancy.     

Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the treatment of mental disorders in pregnant women, but there seems to be an increased risk for neonatal adaptation problems after exposure to SSRIs in late pregnancy. We aimed to investigate the perinatal sequelae of infants exposed to SSRIs during their fetal life and the relationship of these symptoms to the cord blood monoamine and prolactin concentrations. METHODS: We conducted a prospective, controlled, follow-up study with 20 mothers taking 20 to 40 mg/d of either citalopram or fluoxetine for depression (n = 10) or panic disorder (n = 10) and their infants and 20 matched controls not receiving psychotropic medication for confounding obstetric characteristics. Maternal cord blood and infant citalopram, fluoxetine, and norfluoxetine, cord blood monoamine and metabolite, and prolactin concentrations were measured. The newborns underwent standard clinical examination and specific assessment of serotonergic symptoms during the first 4 days of life and at the ages of 2 weeks and 2 months. RESULTS: There was a statistically significant (P =.008, V = 15, n = 20 for both groups), 4-fold difference in the serotonergic symptom score during the first 4 days of life between the SSRI group and the control group. The SSRI-exposed infants had significantly lower cord blood 5-hydroxyindoleacetic acid (5-HIAA) concentrations (P =.02, t31 = 2.57) compared with the control group. A significant inverse correlation (rs = -0.66, P =.007, n = 15) was seen between the serotonergic symptom score and the umbilical vein 5-HIAA concentrations in the SSRI-exposed but not the control infants. CONCLUSIONS: Infants exposed to SSRIs during late pregnancy are at increased risk for serotonergic central nervous system adverse effects, and the severity of these symptoms is significantly related to cord blood 5-HIAA levels.     

Neuroinflammation in the fetus exposed to maternal obsessive–compulsive disorder during pregnancy: A comparative study on cord blood tumor necrosis factor-alpha levels

Objective

The relationship between maternal psychiatric disorders and fetal neurodevelopment is unclear. Obsessive–compulsive disorder (OCD) is relatively frequent during pregnancy. The study aimed to investigate whether maternal OCD during pregnancy affects fetal circulating tumor necrosis factor-alpha (TNF-α) levels, an important pro-inflammatory cytokine, by comparing cord blood TNF-α levels in newborn infants of women with and without OCD.

Methods

The study sample included 7 women with OCD and 30 healthy women. OCD and other psychiatric diagnoses were screened by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The blood sample for the determination of TNF-α level was obtained from the umbilical cord during delivery.

Results

Cord blood TNF-α levels in newborn infants exposed to maternal OCD were significantly higher compared to non-exposed infants. Maternal anxiety symptom level was found to positively correlate with cord blood TNF-α levels in newborn infants of women with OCD.

Conclusion

The study results imply that maternal OCD during pregnancy may lead to neuroinflammation in the developing fetal brain through higher levels of circulating TNF-α.     

Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat

Maternal infection during pregnancy is associated with increased risk for neurodevelopmental disorders. Polyriboinosinic-polyribocytidilic acid (poly I:C) or saline was administered to rats to model maternal infection; levels of TNFalpha, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were determined by ELISA. TNFalpha was significantly increased in maternal plasma, placenta, and amniotic fluid, while it was significantly decreased in fetal liver/spleen and neonatal brain. NGF and BDNF were significantly decreased in the placenta and fetal liver/spleen. There was no change in BDNF or NGF in the fetal or neonatal brain. Changes in TNFalpha, BDNF, and NGF after maternal exposure to poly I:C represent a potential mechanism through which maternal infection increases risk for neurodevelopmental disorders.     

Immunoreactive dynorphine in maternal blood, umbilical vein and amniotic fluid

Immunoreactive dynorphin (ir-Dyn) was measured in maternal blood, umbilical vein and amniotic fluid after its extraction by passage through Sep Pak (C18 Waters). No significant change was observed in the plasma level of ir-Dyn in the first and second trimester of pregnancy as compared with plasma obtained from non-pregnant women. However, a 2.2 fold increase in ir-Dyn levels was observed during the third trimester as well as at delivery (1.07 and 1.09 pmoles per ml, respectively as compared with 0.48 pmoles per ml in control plasma). High levels of ir-Dyn were also found in the amniotic fluid (0.83 pmoles per ml) and the umbilical vein plasma (2.2 pmoles per ml). High pressure liquid chromatography analysis of maternal plasma ir-Dyn obtained at the end of the third trimester of pregnancy revealed the presence of multiple forms of ir-Dyn, the major peaks corresponding to the elution time of some previously identified placental ir-compounds namely Dyn-(1-11) and Dyn-(1-13). These data indicate that the levels of ir-Dyn in the maternal plasma at the third trimester of pregnancy and at delivery increase, a placental contribution to this phenomenon could be speculated.     

Maternal generalized anxiety disorder during pregnancy and fetal brain development: A comparative study on cord blood brain-derived neurotrophic factor levels

Objectives

The study aimed to investigate whether maternal GAD during pregnancy affects fetal circulating brain-derived neurotrophic factor (BDNF), which plays important roles in neuronal development, by comparing cord blood BDNF levels in newborn infants of women with and without GAD.

Methods

Study sample included 19 women with GAD and 25 women without any psychiatric disorder. GAD and other psychiatric diagnoses were screened by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The blood sample for the determination of BDNF level was obtained from the umbilical cord during delivery.

Results

Cord blood BDNF levels in newborn infants of healthy women were approximately two-fold compared to newborn infants of women with GAD, and the difference was statistically significant. The duration of GAD during pregnancy was the only variable correlating with cord blood BDNF levels.

Conclusions

The study results imply that prolonged maternal GAD during pregnancy may negatively influence neurodevelopment of the fetus through lower levels of circulating BDNF.     

Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: possible implications for foetal programming

Both animal and human studies have shown that maternal stress or anxiety during pregnancy is associated with increased risk of disturbance in offspring neurodevelopment and behaviour. In animal models, increased foetal exposure to glucocorticoids has been found to be one mechanism for such foetal programming. Little is understood of the mediating mechanisms in humans, and one aim of our research programme is to investigate this further. This review presents a synopsis of some of our recent results. We aimed to test the hypothesis that maternal anxiety was associated with raised maternal cortisol, and that this in turn was related to increased foetal exposure to cortisol. We studied this by recruiting women at amniocentesis, obtained their Spielberger State Anxiety scores, and assessed maternal plasma cortisol and amniotic fluid cortisol. We also examined maternal plasma and amniotic fluid testosterone levels. Awaiting amniocentesis was in general anxiogenic, but with a wide range of anxiety scores. Maternal anxiety was significantly associated with plasma cortisol before 17 weeks, albeit of modest magnitude (r = 0.0.23), and not after 17 weeks of gestation. This is probably due to the known attenuation of the maternal hypothalamic-pituitary-adrenal axis with increasing gestation. We found a strong correlation between maternal plasma and amniotic fluid cortisol levels, which increased with gestation and became robust after 18 weeks. This correlation increased with maternal anxiety, suggesting a possible effect of maternal mood on placental function. There was a positive correlation between cortisol and testosterone in amniotic fluid, in both male and female foetuses independent of maternal anxiety, plasma testosterone, gestational age, and time of collection. Foetal stress may be associated with increased foetal exposure to testosterone. However, maternal anxiety did not predict amniotic fluid cortisol or testosterone level. Thus, the role of these hormones in mediating the effect of maternal mood on foetal development in humans remains to be demonstrated.     

Pharmacotherapy of depression in pregnancy.

About 20% of pregnant women experience clinical depression. Inadequate treatment of depression has been associated with adverse outcomes in the mother as well as the newborn. Clinicians are often uncertain about pharmacological interventions to treat depressed pregnant women due to concerns regarding fetal exposure to medications. Moreover newer antidepressants with different pharmacological profiles and little data on fetal risk continue to be introduced at a brisk pace. Accumulating data from pharmaceutical registries, cohort studies, toxicology centers, some prospective studies, and case series have permitted certain guidelines for antidepressant use during pregnancy. We review the safety profiles of commonly used antidepressants, discuss clinical decision making based on risk-benefit considerations and make recommendations for pharmacological treatment of depressed women during pregnancy.     

Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury

Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders including cerebral palsy, schizophrenia, and autism. Models of systemic inflammation during pregnancy have demonstrated an association with an immune response an adverse neurobehavioral outcomes for the exposed fetus. Yet, the most common route for an inflammatory exposure to a fetus is from intrauterine inflammation as occurs with chorioamnionitis. The aims of this study were to assess the effect of intrauterine inflammation on fetal and neonatal brain development and to determine if the gestational age of exposure altered the maternal or fetal response to inflammation.CD-1 timed pregnant mice on embryonic day 15 (E15) and E18.5 were utilized for this study. Dams were randomized to receive intrauterine infusion of lipopolysaccharide (LPS, 50 μg/dam) or normal saline. Different experimental groups were used to assess both acute and long-term outcomes. For each gestational age and each treatment group, fetal brains, amniotic fluid, maternal serum and placentas were collected 6 h after intrauterine infusion. Rates of preterm birth, maternal morbidity and litter size were assessed. IL6 levels were assayed in maternal serum and amniotic fluid.An immune response was determined in the fetal brains and placentas by QPCR. Cortical cultures were performed to assess for fetal neuronal injury. Gene expression changes in postnatal day 7 brains from exposed and unexposed pups were determined.In the preterm period, low dose LPS resulted in a 30% preterm birth rate. Litter sizes were not different between the groups at either gestational age. IL6 levels were not significantly increased in maternal serum at either gestational time period. Low dose LPS increased IL6 levels in the amniotic fluid from exposed dams in the term but not preterm period. Regardless of gestational age of exposure, low dose intrauterine LPS activated an immune response in the placenta and fetal brain. Exposure to intrauterine LPS significantly decreased dendritic counts in cortical cultures from both the preterm and term period. Exposure to intrauterine inflammation altered gene expression patterns in the postnatal brain; this effect was dependent on gestational age of exposure.In conclusion, intrauterine inflammation, even in the absence of preterm parturition, can evoke fetal brain injury as evidence by alterations in cytokine expression and neuronal injury. Despite an absent or limited maternal immune response in low dose intrauterine inflammation, the immune system in the placenta is activated which is likely sufficient to induce a fetal immune response and subsequent brain injury. Changes in the fetal brain lead to changes in gene expression patterns into the neonatal period. Subclinical intrauterine inflammation can lead to fetal brain injury and is likely to be mechanistically associated with long term adverse outcomes for exposed offspring.     

Transplacental passage of oxcarbazepine and its metabolites in vivo

PURPOSE: The purpose of this study was to investigate human fetal exposure to oxcarbazepine (OCBZ) in vivo. METHODS: Transplacental passage and placental tissue concentrations of OCBZ and its metabolites were determined. Maternal venous blood, cord blood, and placental tissue samples from 12 mothers using OCBZ during pregnancy alone or in combination with other antiepileptic drugs were collected. Samples were analyzed with high-performance liquid chromatography. RESULTS: Maternal venous concentrations of OCBZ and its major metabolites were at same range as cord blood concentrations (OCBZ in maternal serum, 0.19 +/- 0.16 microg/ml, and in cord serum, 0.21 +/- 0.19 microg/ml; 10-hydroxy-10,11-dihydrocarbamazepine (10-OH-CBZ) in maternal serum, 5.69 +/- 2.49 microg/ml, and in cord serum, 5.23 +/- 1.44 microg/ml; 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (10,11-D) in maternal serum, 0.29 +/- 0.22 microg/ml, and in cord serum, 0.28 +/- 0.14 microg/ml). OCBZ (0.17 +/- 0.16 microg/g placental tissue), 10-OH-CBZ (3.49 +/- 1.34 microg/g placental tissue) and 10,11-D (0.25 +/- 0.11 microg/g placental tissue) were detected in the placental tissue. The amount of OCBZ detected from placental tissue was 0.01% of the daily dose. CONCLUSIONS: OCBZ, like other antiepileptic drugs, is transferred significantly through the placenta in humans.     

Effect of maternal sleep in late pregnancy on leptin and lipid levels in umbilical cord blood

ObjectivesTo study the impact of maternal sleep in late pregnancy on birth weight (BW) and leptin and lipid levels in umbilical cord blood.Study designA total of 277 healthy and singleton pregnancy women were recruited for participation in the Shanghai Sleep Birth Cohort Study (SSBC) during their 36–38 weeks of pregnancy, from May 2012 to July 2013. Maternal night sleep time (NST), sleep efficiency (SE), sleep onset latency (SOL) and the percentage of wake after sleep onset (WASO) in NST and midpoint of sleep (MSF) were measured by actigraphy for seven consecutive days. The leptin and lipid levels were determined in cord blood samples collected from the umbilical vein immediately after delivery. Birth information (birth weight, gender, delivery type, etc.) was extracted from medical records. A multivariable linear regression model was applied to examine the effect of maternal sleep in late pregnancy on newborn leptin and lipid levels in umbilical cord blood.ResultsA total of 177 women and their infants were included in the analysis. Maternal mean NST was 7.03 ± 1.10 h in late pregnancy, and 48% had a shorter sleep time (NST < 7 h). The average maternal SE was 72.54% ± 9.66%. The mean percentage WASO/NST was 21.62% ± 9.98%; the average MSF was about 3:34 (0:53); and the SOL was 46.78 ± 36.00 min. After adjustment for confounders, both maternal NST and SE were found to be significantly associated with triglyceride levels (β = −0.219, p = 0.006; β = −0.224, p = 0.006) in umbilical cord blood; and maternal NST was also observed to have positive association with newborn leptin levels (β = 0.146, p = 0.047). However, we did not find significant association between other maternal sleep parameters in late pregnancy and leptin and lipid levels and birth weight.ConclusionsShort sleep duration and poor sleep quality during late pregnancy were associated with newborn leptin and lipid levels, and efforts on improving maternal sleep during late pregnancy should be advocated for children's health.     

Maternal use of antidepressant or anxiolytic medication during pregnancy and childhood neurodevelopmental outcomes: a systematic review

Antidepressant and anxiolytic medications are widely prescribed and used by pregnant women for acute and maintenance therapy. These drugs are able to pass the placental barrier, and may potentially influence fetal and brain development. It is possible that exposure to prenatal antidepressants or anxiolytic medication may disturb neurotransmitter systems in the brain and have long-lasting consequences on neurodevelopment in the offspring. As all medication during pregnancy may pose a certain risk to the developing fetus, the potential benefits of the medication must be weighed against the risks for both mother and her unborn child. Therefore, information to guide patients and physicians to make a well-balanced decision for the appropriate treatment during pregnancy is needed. In this systematic review, an overview of maternal use of antidepressant or anxiolytic medication during pregnancy and childhood neurodevelopmental outcomes is provided. Some studies indicate a relation between prenatal exposure to antidepressants and adverse neurodevelopmental outcomes such as delayed motor development/motor control, social difficulties, internalizing problems and autism, but cannot rule out confounding by indication. Overall, the results of the observational studies have been inconsistent, which makes translation of the findings into clinical recommendations difficult. More well-designed observational studies and also randomized controlled trials (e.g., maintenance treatment vs. cessation) are needed to move forward and provide a comprehensive evaluation of the risks and benefits of antidepressant and anxiolytic use during pregnancy.     

Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam

The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women.