Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine
Introduction
According to the 2005 National Survey on Drug Use and Health (NSDUH), an estimated 512,000 people in the United States over the age of 12 used methamphetamine the previous month, 192,000 being new users [58]. Additionally, an estimated ten million people have used methamphetamine at least once in their lifetime [58]. Methamphetamine (MA) use has been associated with an increase in high risk behavior resulting in a rise in HIV transmission [8] and numerous other health problems including seizures, weight loss, paranoia and depression [57]. The NSDUH estimated that 3.9% of pregnant women ages 15 to 44 years reported using illicit drugs in the past month [58]. To date, little is known regarding the effects of prenatal MA exposure on the developing child.
The effects of prenatal MA exposure on the developing fetus have not been well characterized. Fetal growth restriction, and decreased arousal, increased stress, and poor quality of movement on the NICU Network Neurobehavioral Scale (NNNS) has been reported in MA-exposed neonates [52], [55]. In children exposed to prenatal amphetamine, Billing and colleagues found lower IQ test scores at 4 years of age compared to the unexposed children (103 vs. 110, respectively) [7]. These data reported in older children are limited by small sample size, lack of a control group and confounding with other prenatal drug exposures.
The NSDUH reported that illicit drug use was higher among adults with serious psychological distress as compared to those without (26.9% vs. 12.1%, respectively) [58]. Zweben and colleagues reported 34% of MA-using women displayed depressive symptoms upon entry into drug treatment programs [60]. Positron emission tomography scans have shown MA users have a reduction in dopamine transporters. Symptoms related to reduced dopamine transporters mimic those of depression [50], [60]. In addition, Volkow and colleagues found that depressive symptoms are not only present after an episode of MA use, but can persist for several months after abstinence [59]. Since depression is highly correlated with MA use, the depression associated with MA use during pregnancy may be associated with adverse effects in exposed infants.
Depression during pregnancy is associated with less spousal support [43], increased anger and anxiety episodes [21], [22], and more stressors in the areas of work, health, family, friends and environment [12]. Antepartum depression is associated with less prenatal care, more obstetric complications, preterm labor, less weight gain during pregnancy, and increased use of drugs, alcohol and tobacco compared to mothers with little or no prenatal depression [2], [22], [23], [29], [48], [56]. Field and colleagues found increased fetal activity, physiological activity and fetal heart rates, and delayed growth in fetuses of mothers who are depressed [23]. Neonates of mothers who were depressed during pregnancy are at greater risk for low birthweight (< 2500 g) and being small for gestational age (< 10th percentile) [23]. These growth impairments have been shown to continue throughout the first year of life [23], [30] potentially leading to long term health complications in the child.
The effect of prenatal depression on infants has also been examined. Hurley and colleagues found that WIC participants with depressive symptomatology were more likely to exhibit forceful, indulgent and uninvolved feeding style scores [31]. In addition, the increased fetal cortisol levels associated with maternal depression have been associated with an inhibited or fearful temperament and less positive affect after birth [23], [30]. Prenatal depression is also associated with less optimal infant scores for orientation, reflexes, excitability and withdrawal on the Brazelton Neonatal Behavioral Assessment Scale [23]. The underlying mechanisms causing the differences in neonates of depressed mothers during the prepartum period have been evaluated. Depressed women have higher cortisol and norepinephrine levels and lower dopamine levels than non-depressed women, creating an imbalance in the chemicals in the prenatal environment [23]. Cortisol is involved with the complex pathways of hypothalamic-pituitary axis (HPA) and sympathoadrenal dysregulation. It has been hypothesized that elevated cortisol may cross the placenta and affect fetal growth by dysregulating fetal autonomic nervous system activity which may lead to fetal HPA reprogramming and altered nervous system development [23], [38]. In addition, higher norepinephrine levels affect the cardiovascular system of the neonate [23]. Diego and colleagues found that newborns of mothers with depressive symptoms had elevated urine cortisol and norepinephrine levels and lower dopamine levels, mimicking the biochemical profile of their depressed mothers [2], [23]. In addition, infants in the prepartum group demonstrated greater relative right frontal electroencephalogram (EEG) asymmetry which had been found to be associated with a disposition towards behavioral inhibition and negative affect later in life [13], [14], [25]. These findings suggest prenatal maternal depression can influence an infant's neurobehavior starting in utero.
Although the effects of prenatal MA use during pregnancy and the increased incidence of depressive symptoms associated with MA use have been reported, no prior research has investigated the impact of maternal depressive symptoms on the neurodevelopment of neonates exposed to MA during pregnancy. The Infant Development, Environment, and Lifestyle (IDEAL) study is a prospective longitudinal study investigating the effects of prenatal MA exposure. To our knowledge, this is the first study to look at the effects of maternal depressive symptoms on neurodevelopment in MA exposed neonates. We hypothesized that maternal depressive symptoms would be associated with differences in neonatal neurodevelopment. Additionally, we hypothesized that MA use and maternal depression in combination would be associated with poorer neonatal neurodevelopment relative to infants born to non-depressed MA using women.
Section snippets
Study design
Since the purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome, clinical sites were chosen to participate in specific geographical areas known to have high MA use. The cities chosen were Los Angeles, CA; Des Moines, IA; Tulsa, OK; and Honolulu, HI. The study was approved by the Institutional Review Boards at all participating sites. Prior to initiation of recruitment, personnel from all sites met for a week-long training session to standardize
Maternal and infant characteristics
Maternal characteristics of the 136 biological mothers are reported in Table 1. Since we matched for race, insurance status, and education level, it was expected we would find no differences between groups. In addition, no differences were observed with number of prenatal visits, maternal height and age, and pre-pregnancy weight. Relative to the comparison group, MA using mothers were more likely to be of a lower social economic status (SES), have higher incidence of depression and experience
Discussion
In western societies, the prevalence of depressive symptomatology during pregnancy has been found to be as high as 25% [9], [12], [23], [26], [27], [28], [56]. Hormonal changes associated with the reproductive cycle, especially those accompanied by pregnancy, can increase the vulnerability for the onset or recurrence of depression [6]. Women who are diagnosed with depression at approximately one month postpartum are more likely to have been depressed during pregnancy [12], [26], [48], [49],
Acknowledgements
This study was supported by NIDA Grant# 1RO1DA014918 and in part by the National Center on Research Resources, Grant # 3 M01 RR00425 and P20 RR11091.
Conflict of interest
Nothing declared.
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