The impact of prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure and maternal mood on mother–infant interactions at 3 months of age
Introduction
Interactions between mothers and their infants play a critical role in shaping early social–emotional regulation. Maternal apathy, helplessness and irritability associated with depressed mood adversely influence the cognitive, social and emotional development in early childhood via maladaptive interaction and attachment patterns (Martins & Gaffan, 2000). Maternal mood disturbances are experienced in approximately 10–20% of pregnancies (Oberlander, Warburton, Misri, Aghajanian, & Hertzman, 2006), and increasingly serotonin reuptake inhibitor (SRI)1 antidepressants are used to treat these disorders (Oberlander, Gingrich, & Ansorge, 2009). This raises critical new questions about the impact – whether positive or negative – such treatment may have on the developing infant.
Maternal mood shapes fetal neurobehavioral development in both negative (DiPietro et al., 1996, Tronick and Weinberg, 1997) and positive directions (DiPietro, Novak, Costigan, Atella, & Reusing, 2006). Behavioral reactivity in utero is also altered (Allister et al., 2001, Monk et al., 2000) and the risk for premature birth increases (Glover, 2011, Talge et al., 2007). During the first year of life, prenatal maternal mood predicts infant temperament and attention regulation (Austin and Priest, 2005, Davis et al., 2007, Pluess et al., 2011, Talge et al., 2007), even when accounting for postnatal maternal mood. Well into childhood, prenatal maternal mood still influences cognitive, behavioral and emotional outcomes (Talge et al., 2007) when accounting for obstetric risk, psychosocial disadvantage and postnatal maternal mood. Mechanisms by which prenatal mood influences early brain development remain unclear, yet the magnitude of the effect is clinically significant, with approximately 15% of emotional and behavioral problems in childhood attributable to prenatal mood (Talge et al., 2007).
Infants of depressed mothers show less positive affect and this extends over the first year of life (Abrams et al., 1995, Field et al., 2006). In the postpartum, infants of depressed mothers show fewer positive facial expressions, are less attentive and show increased distress during mother–child interactions (Field, 1984). Early maternal sensitivity (both impaired and typical) in response to her infant's signals has been associated with later mother–infant attachment and subsequent behavioral development during infancy (Ainsworth, 1979, Pederson et al., 1998, Wolff and Ijzendoorn, 1997) and childhood (Murray et al., 1996a, Murray et al., 1996b, Olson et al., 1984).
Beyond mood disturbances, pharmacotherapeutic treatments also influence early infant behavior (Oberlander et al., 2009). SRIs are estimated to be prescribed in 5–13% of pregnancies (Cooper, Willy, Pont, & Ray, 2007), and readily cross the placenta and blood brain barrier (Kim et al., 2006). SRIs block the intrasynatpic reuptake of the neurochemical serotonin which acts as a neurotrophic factor involved in early brain development (Gaspar, Cases, & Maroteaux, 2003). This raises critical questions about the developmental impact of altered central serotonin during critical periods of neurodevelopment (Oberlander et al., 2009). While SRIs are often considered for prenatal therapy with the goal of improving maternal mental health during pregnancy (Gentile, 2005), such treatment has been shown to result in remission of a major depressive disorder in only 37% of patients and an overall cumulative remission rate of 67% (Rush et al., 2006). Thus, beyond gestational SRI exposure, ongoing maternal mood disturbances may place the infant's neurobehavior at continued risk during childhood.
While SRIs are not associated with gross neurological malformations (Bellantuono et al., 2007, Simon et al., 2002), neonatal neurobehavioral disturbances, referred to as “poor neonatal adaptation”, have been widely reported (Moses-Kolko et al., 2005, Nordeng and Spigset, 2005). Currently, very little is known about the impact of prenatal SRI exposure on early social–emotional regulation. In a single study of maternal–infant interactions following prenatal SRI exposure, maternal differences in positive and negative responses were only apparent when the mothers were treated with multiple prenatal psychotropic medications (SRIs and benzodiazepines) (Reebye, Morison, Panikkar, Misri, & Grunau, 2002). Importantly, the impact of prenatal maternal mood was not reported and it remained unclear whether the outcomes were influenced by SRI exposure alone. According to analogous research, prenatal exposure to cocaine (a pharmacological analog to SRIs that acts as a nonselective drug that also inhibits serotonin reuptake) (Barker & Blakely, 1995), has been associated with mothers who were less attentive and interrupted more frequently, and their cocaine exposed infants were less willing to interact (Mayes et al., 1997).
The present study was undertaken to study the impact of SRI treatment on early social–emotional development as reflected by mother–infant interactions, while accounting for both prenatal and postnatal maternal mood. When their infants were 3 months of age, we studied mother–infant interactions in a cohort of mothers who had been depressed and treated with an SRI antidepressant. This group (SRI-exposed) was compared to the dyadic behaviors of mothers who had a range of depression symptoms (including non-depressed and depressed) and had not received an SRI during pregnancy (non-SRI-exposed). Variation in depression symptoms in the non-exposed group allows us to better separate SRI exposure effects from the potential impact of maternal mood. If prenatal exposure to SRI medications has an influence on the development of infant interactive behaviors, we expected infants to show differential responses during our interaction paradigm. Similarly, if SRI treatment changes maternal interaction patterns, we expected mothers treated with SRIs to interact with their infants differently. The impact of maternal mood was controlled for in all analyses in order to determine if interactions between maternal mood and both maternal and infant behavior differed depending on SRI treatment status.
Section snippets
Participants
With approval from the University of British Columbia Research Ethics Board, Children's and Women's Health Centre of British Columbia Research Review Committee, and informed parental consent, mothers were recruited in their second trimester as part of a prospective study of infant development following prenatal antidepressant medication exposure. The mothers had originally been recruited in the second trimester (mean weeks 24.14 (SD = 4.67)). Originally 99 mothers were recruited, 19 moved away or
Maternal and infant characteristics
Mother and infant characteristics are listed in Table 3. In the non-exposed group, maternal depression scores (HAMD) were significantly lower pre and postnatally. Additionally, maternal educational achievements were higher, the infants were more likely to be first born, with greater neonatal 5-min APGAR scores and older gestational ages at birth in the non-exposed group. The variables that were significantly different between groups were used as covariates in the MANCOVAs. Mothers treated
Discussion
This study examined the impact of prenatal SRI antidepressant treatment and maternal mood (both pre and postnatal) on mother–infant interactions at 3 months. Two key findings emerged. First, when controlling for the influence of both pre and postnatal mood, mothers treated with an SRI showed more interruptive and forcing behaviors toward their infants. Secondly, maternal mood had an impact on infant readiness to interact at 3 months. In the non-SRI exposed group, increased maternal symptoms of
Conclusions
Mothers treated prenatally with SRIs appear to interrupt their infants more during mother–infant interactions. Furthermore, increased third trimester maternal depressed mood (in spite of SRI treatment), was associated with an increased infant willingness to interact. In contrast, among non-exposed infants, higher postnatal maternal depressed mood was associated with less willingness to interact. Whether our findings reflect altered fetal serotonin signaling (secondary to SRI exposure) or the
Funding sources
Research funded by March of Dimes Foundation (USA) and the Canadian Institutes of Health Research (TFO (PI), CIHR #MOP 57837). TFO is supported by a HELP (Human Early Learning Partnership) Senior Career Award and is the R. Howard Webster Professor in Brain Imaging and Early Child Development (UBC). WMW was supported by postdoctoral fellowships from CIHR, Michael Smith Foundation for Health Research and funding from the Sunny Hill Foundation. REG holds a Senior Scientist salary award from the
Conflict of interest statement
None of the authors have conflicts of interest, including financial interests that are relevant to the study reported in this manuscript. Study sponsors had no role in study design; data collection, analysis or interpretation; in the writing of the paper; and in the decision to submit the paper for publication.
Acknowledgments
None of this work would have been possible without the mothers and their infants who gave generously of their time, and the thoughtful work of Dr. Shaila Misri and Victoria Nethercott who were central to recruitment and data collection and to Kathy Armstrong and Irik Sielski for Mother-Infant Interaction coding.
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