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Important Articles for PMHNP Students

Interpersonal Interventions and Pregnancy/Postpartum

Article Number Author/Year Therapy Findings
1 Lilliecreutz, Josefsson, & Sydsjo, 2010 CBT group therapy for pregnant woman with blood and injection phobia

Two sessions CBT
The injection Phobia Scale-Anxiety (IPSA) and Injection Phobia Scale Avoidance (IPSAV) were reduced over study (p<0.001), before and after the two treatment sessions (p<0.001), and at the follow-up 3 months postpartum (p<0.001) compared to first and second session. The beck Anxiety Inventory (BAI) score were reduced over time (p<0.001) after adjustments for parity and age. The Edinburgh Postnatal Depression Scale (EPDS) score reduced over time (p<0.001) especially among nullipara even after adjustment for age.
2 Mulcahy, Reay, Wilkinson, & Owen, 2010 IPT group therapy for postnatal depression (MDD).

Eight weeks
By the end of treatment there was improvement in levels of depression in IPT-G participants: EPDS (t (22) = 7.637, p<0.05; 95% CI 5.26-9.17), and BDI-II (t (22) =6.940; p<0.05; 95% CI 8.78-16.27). The IPT-G participants reported significantly higher levels of marital functioning compared to treatment as usual (TAU) participants at the end of therapy (p<0.05; 95%CI 2.164 to 19.848). IPT-G participants continued to improve with significantly decreased levels of depression using the EPDS (p<0.01; 95% CI -4.19 to -.62), and BDI-II from end of treatment to three-month follow up (p<0.001, 95% CI 3.24-8.47) and decreased compared to TAU control group at three month follow up (p<0.001, 95% CI -17.14 to -5.51).
3 Nylen et al., 2010 IPT

Twelve one hour sessions over 12 week period
Among the 35% of women who recovered with treatment (n=35), 15 (43%) experienced a recurrence primarily between 10-50 weeks post-treatment. Among the 65% who did not recover with treatment (n=64), 54 (84.4%) recovered primarily between 10 to 35 weeks in the follow up period. Significant predictors of overall time depressed included post-treatment depression severity, greater number of past major depressive episodes, and more weeks of treatment during follow-up.
4 Grote, Swartz, Geibel, Zuckoff, Houck, & Frank, 2009 Culturally enhanced brief interpersonal psychotherapy (IPT-B)

Eight sessions
IPT-B group had higher rates of treatment engagement and retention than usual care group (68%, 7% respectively) completing a full course. At three months post-baseline (before childbirth) the 95% of the intervention group compared to 58% of the usual care group did not meet criteria for MDD on the SCID (x2=.96; df=1; p<0.003; cohen’s h=0.96). At six months postpartum 0% of the intervention group compared to 70% of the usual care group had MDD (x2=7.92, df=1, p<0.05; cohen’s h = 1.22).
5 Le, Stuart, & Perry, 2011 CBT psychoeducation group sessions

Eight weekly two hour sessions
Treatment group had lower depressive symptoms at post intervention during early and late depression post intervention than non treatment (Cohen’s d = -0.28, p=0.03). There was no significant effect of CBT evident in postpartum period in intervention group over non-intervention group.
6 Field et al., 2009 IPT Group therapy sessions

One hour once a week for Six sessions.
Overall CES-D scores decreased from first session mean 20.33 (SD: 10.10) compared to last session mean 18.00 (S: 10.66). CES-D scores of depressed affect decreased from mean 6.17 (SD: 4.57) first session to mean 4.67 (SD: 3.89) last session. Anxiety (STAI) score also dropped from first to last session mean 42.00 (SD: 9.98) to mean 39.52 (SD: 10.88).CES-D somatic vegetative and interpersonal distress rose slightly from first to last sessions. CES-D positive effect dropped slightly from first to last session.
7 Chen, & Hao, 2010 IPT-oriented childbirth education program

Two 90-minute antenatal classes and a telephone follow-up within two weeks after delivery.
Comparing control versus treatment group at six weeks postpartum scores were significantly lower in the treatment group for Edinburgh Postnatal depression scale (EPDS) depressive symptoms (p=0.0000; 95% CI: -3.48 to -1.09) and Satisfaction with Interpersonal Relationships Scale (SWIRS) (p=0.001; 95% CI: 0.31 t0 1.25).
8 Moel, Buttner, O’Hara, Stuart, & Gorman, 2010 Group IPT

12 weeks
Following 12 weeks of treatment with IPT interest in sex increased irrespective of recovery status (t(df=104)= - 3.18, p<0.01) and marital satisfaction improved t(df=89)=2.75, p<0.01). Depressed women, both recovered and non-recovered remained significantly less satisfied in their relationships with their partners after 12 weeks of IPT treatment compared to never depressed women (p<0.0001).
9 Ayers, McKenzie-McHarge, & Eagle, 2007 Case one:
CBT: 10 sessions

Case two:
CBT: 12 sessions
After 10 sessions of CBT patients symptoms of PTSD disappeared and her beliefs about herself and others were modified.

After 12 sessions of CBT patients symptoms of PTSD disappeared, her depression lesson, and her relationship with her husband was much improved.
10 Austin et al., 2008 Brief antenatal CBT group intervention

Six weekly two hour sessions and a later follow-up session
There were no significant differences in improvement between the CBT and control group.

Adverse Effects of Psychotropic Medications

Article Number Author/Year Medication Findings
1 Newport et al., 2008 Lamotrigine The milk/plasma (M/P) ratios demonstrated wide variability ranging from a low of 5.8% to 147.1%. Significant predictors of lamotrigine breast milk concentration were maternal dose (F1,147=25.62; P,.0001), free lamotrigine concentration in maternal plasma (F1,147=17.31; P<.0001), and the interaction of these 2 predictors (F1,147=6.44; P<.02).
2 Holmes et al., 2008 Lamotrigine Total of 16 (2.3%) of 684 infants exposed to lamotrigine had major malformations that were identified at birth. Five infants (7.3/1,000) had oral clefts; isolated cleft palate (3), isolated cleft lip (1), and cleft lip and palate (1). There was a 10.4-fold increase (95% CL: 4.3-24.9) in comparison to 206,224 unexposed infants surveyed at birth with a prevalence of oral clefts 0.7/1,000.
3 Fotopoulou et al., 2009 Lamotrigine There was a significant increase in total LTG-clearance between non-pregnant baseline and the two last trimesters of pregnancy with the highest values recorded at delivery (median total LTG-clearance by 264% above the non-pregnant baseline). The first, second, and third trimester increase of median LTG-clearance 197%, 236%, and 248% above the non-pregnant baseline respectively. At the time of delivery median peak clearance values reached 264%, and during the first 7 days decreased to 218% above non-pregnant baseline. Pre-conceptional values were not reached until the 3rd week postpartum. Median ratio of breast milk to maternal serum of 0.59 (IQR: 0.38-0.70). LTG-SC in the breastfed newborn ranged between 1.7 to 3.3ug/ml (median 2.2ug/ml) during first 12 weeks postpartum.
4 Dolk et al., 2008 Lamotrigine There was no evidence of an increased risk of isolated orofacial cleft relative to other malformations with LTG monotherapy versus no antiepileptic drug exposure (OR=0.80, 95% CI 0.11-2.85). No increased risk of any of the other three categories of orofacial cleft. There were three significant differences in LTG group (mono and polytherapy): the following were in excess; spina bifida (p<0.01), cystic kidney (p<0.05), and clubfoot (p<0.05).
5 Almgren, Kallen, & Lavebratt, 2009 Antiepileptic drugs Carbamazepine had the strongest negative effect on birth weight-adjusted head circumference. Valproic acid in monotherapy also had a negative effect on mean birth weight-adjusted head circumference. Phenytoin, clonazepam, lamotrigine, and gabapentin in monotherapy showed no effect on mean body weight-adjusted head circumference.
6 Calderon-Margalit et al., 2009 Psychotropic medications SSRI therapy was associated with low birth weight among women who started treatment in second and third trimesters. SNRI venlafaxine was associated with low 5-minute Apgar scores and possible NICU admissions and RDS. Benzodiazepines were associated with low 5-minute Apgar scores, NICU admissions, and RDS.
7 Newham et al., 2008 Antipsychotic medications There were significantly more large for gestational age infants among those exposed to atypical antipsychotics in utero than those exposed to typical antipsychotics or reference agents (especially clozapine and olanzapine)
8 Lin et al., 2009 Antipsychotic medications There was no significant difference in the risk of low birth weight, preterm births, large for gestational age, and small for gestational age babies compared to mothers with schizophrenia receiving atypical antipsychotics during pregnancy and those not receiving antipsychotics. Mothers with schizophrenia receiving typical antipsychotics during pregnancy had a higher odds of preterm birth (OR=2.46, 95% CI=1.50-4.11) compared to those not receiving antipsychotics.
9 Wisner et al., 2009 Antidepressants Infants of mothers with SSRI exposure or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Continuous SSRI or depression did not increase risk for minor physical anomalies or abnormal maternal weight gain. Significantly more infants had Apgar scores of 7 or more at 5-minutes among infants born to mothers with continuous exposure to SSRI than among unexposed infants.
10 Warburton et al., 2009 SSRI There was an increased risk for neonatal respiratory distress if SSRI exposure continued past last 14 days compared to stopping prior to last 14 days of pregnancy. However, after controlling for maternal and neonatal confounders the significance disappeared.
11 Toh et al., 2009 Antidepressants There were no elevated risk of preterm labor or small for gestational (SGA) age baby stopped SSRI prior to end of first trimester. If continued SSRI during pregnancy there was an increased risk of delivering a SGA baby, crude OR 2.75 (95% CI, 1.56-4.84) and adjusted OR 3.01 (95% CI, 1.65-5.47), crude ORs for preterm delivery were 2.13 (95% CI, 0.89-5.08) for TCAs and 2.32 (95% CI, 0.51-10.50) for SNRIs. The ORs for SGA were 1.37 (95% CI, 0.49-3.85) for TCAs and 5.78 (95% CI, 1.77-18.84) for SNRIs.
12 Rein & Kallen, 2010 Antidepressants Paroxetine had a statistically increased risk for hypospadias after exposure OR 2.45 (95% CI, 1.12-4.64). The risk for a relatively severe malformation, for any cardiovascular defect, and for a ventricular (VSD) or atrial septal defect (ASD) were significantly increased only for TCAs (primarily clomipramine)
13 Pedersen et al., 2009 SSRIs SSRIs were associated with septal heart defects (OR 1.99; 95% CI 1.13-3.53). There was an increased prevalence of septal heart defects for children of women who used sertraline (OR 3.25; 95%CI 1.21 to 8.75) and citalopram (OR 2.52; 95%CI 1.04 to 6.10).

Redemption of more than one type of SSRI was associated with increased heart malformations (3.42, 1.40 to 8.34) especially septal heart defects (OR 4.70; 95% CI 1.74 to 12.7).
14 Pendersen, Henriksen, & Olsen, 2010 Antidepressants At 6 months of age, children of mothers who used antidepressants during pregnancy were unable to sit without support (OR: 2.1 [95% CI: 1.23-3.61]) compared to children of mothers with untreated depression. At 19 months children exposed to antidepressants during second or third trimester were unable to occupy themselves for >15minutes (OR: 2.1 [95% CI: 1.09-4.02]) compared to children of mothers with untreated depression.
15 Newport et al., 2009 Venlafaxine Breast milk desvenlafaxine concentration was positively correlated with the desvenlafaxine concentration in maternal plasma and with maternal daily venlafaxine dose, but was negatively correlated with the venlafaxine concentration in maternal plasma, weeks postpartum, and the venlafaxine concentration in breast milk.
16 Lund, Pedersen, & Henriksen, 2009 SSRIs Mean gestational age was 4.5 days shorter in women treated with SSRIs during pregnancy than women without a psychiatric history. Women treated with SSRIs had twice the risk of preterm delivery than women with no history of psychiatric illness. Risk of 5-minute Apgar scores of 7 or below were increased in infants of women treated with SSRI during pregnancy compared with infants of women with no psychiatric history or history without SSRI use. NICU admissions rate was higher in infants exposed in utero to SSRIs than those without psychiatric history.
17 Lobo et al., 2008 Duloxetine Duloxetine exposure in breast milk was approximately ¼ of the concentration observed in plasma. Mean daily amount of duloxetine in breast milk (40 mg twice daily) was approximately 7.4 ug (range 3.6 -15 ug). Mean estimated infant dose was approximately 2 ug/kg/day, which is approximately 0.14% (maximum 0.25%) of the maternal dose (1.21 mg/kg/day).
18 Hale et al., 2010 Antidepressants Women who took antidepressants while pregnant and breastfeeding were 2-8 times more likely to report symptoms of discontinuation syndrome in their infants than women who only took them while breastfeeding (jitteriness, vomiting, irritability, low body temperature, shivering, and problems with eating and sleeping). Women who took medications with a longer half life had decreased odds of their infant experiencing jitteriness and stiffness compared to a short half life. More stiffness was reported in infants if mothers started taking an antidepressant during the second and third trimesters compared to those who started in the first trimester or earlier.
19 Galbally, Lewis & Buist, 2011 Antidepressants Infants exposed in utero to antidepressants scored lower on motor subscales, fine motor, than non –exposed infants, but the numbers were not statistically significant.
20 Freeman et al., 2008 Sertraline The general mean decrease in serotonin serum levels as pregnancy progressed that was not statistically significant. Lowest dose-adjusted levels were seen primarily in the third trimester when compared to second trimester and postpartum.
21 Figueroa, 2010 Antidepressants Bupropion exposure during pregnancy (OR: 3.63, p=.02) especially second trimester (OR: 14.66, p<.001) was strongly associated with increased risk of ADHD in offspring but not during the first and third trimester and compared SSRIs (OR: 0.91, p= .74). A total of 4.39% of offspring exposed to bupropion during pregnancy were diagnosed with ADHD by age 5 years compared to only 2.51% in offspring of mothers who used SSRIs, and 2.49% born to depressed mothers not exposed to antidepressants during pregnancy. Maternal smoking while taking bupropion may be a confounding factor.
22 Einarson et al., 2008 Paroxetine Rate of cardiovascular defects in teratology information services cohort in exposed group 0.7%, in unexposed group 0.7%. Research support from Wyeth and Janssen-Ortho and Pfizer
23 Einarson et al., 2009 Antidepressants No increased risk of specific malformation associated with individual antidepressant.
24 Boucher et al., 2008 Antidepressants There was an increased risk of alertness alteration (OR 37; 95% CI 8-174), altered muscular tone (OR 20; 95% CI 5-71), feeding and GI problems (OR 3.8; 95% CI 1.7-8.1), tachypnea (OR 2.5; 95% CI 1.1-5.3), and neurological problems (9/73 vs 0/73; P = 0.006).
25 Andrade et al., 2008 Antidepressants 6.6% women were given an antidepressant during pregnancy (5.1% during first trimester, 3.8% during second trimester, and 4.1% during third trimester. The number of women using an antidepressant during pregnancy has raised since19996 at 2%.
26 Andrade et al., 2009 Antidepressants Of mothers who used SSRIs 2.14/1,000 cases had persistent pulmonary hypertension of newborn (95% CI 0.26- 7.74), and unexposed infants 2.72/1,0000 cases (95% CI 0.56-7.93)
27 Tomson et al., 2011 Valproate and lamotrigine The lamotrigine dose/plasma concentration (D/C) was higher among those treated with lamotrigine alone compared to those treated with lamotrigine/valproate combination throughout pregnancy.
28 Kacirova, Grundmann, & Brozmanova, 2010 Lamotrigine Co-administration of VPA increased infant and maternal serum levels of LTG but not infant/maternal (I/M) ratio. VPA decreased LTG clearance by approximately 65%.

Co-administration with carbamazepine increased LTG clearance but non-significantly. Infant serum concentrations of VPA were 30% higher than maternal serum concentrations. Infant serum concentrations of carbamazepine were 20% lower than maternal serum concentrations
29 Veiby et al., 2009 Antiepileptic drugs (AEDs) Infants in epilepsy group had lower mean birth weight compared to controls (p<0.001). Low birth weight, small head circumference, and prematurity were significantly increased in AED exposed infants, especially in polytherapy or with carbamazepine (p<0.001). Women in epilepsy group had higher rates of preeclampsia especially in those exposed to carbamazepine (p<0.001).
30 Molgaard, Nielsen, & Hviid, 2011 Antiepileptic drugs (AEDs) Of infants exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam during the first trimester, 3.2% were diagnosed with a birth defect compared to infants not exposed at 2.4%. A major birth defect was diagnosed in 3.7% of infants exposed to lamotrigine, 2.8% exposed to oxcarbazepine, 4.6 exposed to topiramate, 1.7 exposed gabapentin, and zero exposed to levetiracetam.
31 Forsberg, Wide, & Kallen, 2011 Antiepileptic drugs (AEDs) Lower grades in math (z=2.43, p=0.02), English (z=2.29, p0.003), and Swedish (z=3.62, p<0.001) in carbamazepine group compared to phenytoin group.
32 Bakker et al., 2010 Fluoxetine Three children of 178 cases with infantile hypertrophic pylorus stenosis (IHPS) were exposed to fluoxetine in the first trimester (1.7%) compared to eight fluoxetine exposures in 4077 registrations with other malformations (0.2%) with a difference of (p=0.009, OR=8.7, 95% CI 2.3-33.2). Out of the three children with IHPS two of them had a familial occurrence, two of the mothers smoked. Once adjusted for smoking and maternal age (OR=9.8, 95% CI: 1.5-62.0).
33 Wichman et al., 2009 SSRIs and venlafaxine There was no significant association between Congenital heart disease (CHD), ventral septal defect (VSD), Persistent pulmonary hypertension of newborn (PPHN), and SSRI use during pregnancy.
34 Merlob et al., 2009 SSRIs Compared to non-exposed infants, infants exposed in utero to SSRIs were at an increased risk for mild congenital heart defect (RR, 2.17; 95% CI: 1.07-4.39). Eight of the 235 newborns exposed to SSRI in the first trimester had congenital heart malformations, paroxetine 4 infants, fluoxetine 2 infants, sertraline and citalopram 1 infant each. Cardiac anomalies in exposed infants were 4.3% paroxetine and 2.0% fluoxetine. VSD in 6 of the exposed infants, with paroxetine 3 infants, two fluoxetine, and one to citalopram.
35 Diav-Citrin et al., 2008 Fluoxetine and paroxetine After logistic regression the only significant predictors for risk of congenital anomalies in the form of cardiovascular anomalies, were smoking more than 10 cigarettes a day (OR 5.40, 95% CI: 1.76-16.54) and exposure to fluoxetine (OR 4.47, 95% CI 1.31-15.27).
36 Bakker et al., 2010 Paroxetine Adjusted OR for Atrial septal defect (ASD) (AOR 5.7; 95% CI: 1.4-23.5) after use of paroxetine during the first trimester of pregnancy.
37 Rampono & Teoh, 2011 Desvenlafaxine The mean milk/plasma distribution ratio was (OR 2.24; 95% CI 2.05-2.43). Desvenlafaxine concentration in hindmilk/foremilk was (OR 0.93; 95%CI 0.86-1), corresponding to a median (IQR) hindmilk/foremilk creamatocrit ratio (OR 1.9; 95% CI 1.5-7.3).
38 Boucher et al., 2009 Venlafaxine Five out of seven neonates had adverse reactions that emerged as drug concentration was decreasing, possibly due to discontinuation syndrome. One infant had respiratory distress initial intermittent, 4 multiple clinical signs (tachypnea, respiratory distress), and 2 with no adverse effects. Three neonates were evaluated for elimination half life of venlafaxine (12-15hrs) active metabolite (10-37 hrs).
39 Hilli et al., 2009 Citalopram and fluoxetine Monoamine oxidase type A (MAO-A) genotype showed association with occurrence and magnitude of perinatal serotonergic signs and symptoms after in utero exposure to fluoxetine or citalopram (p=0.024). Infants with high activity MAO-A alleles showed higher cord blood dihydroxyphenylglycol  (DHPG) concentrations (p=0.0054).  MAO-A genotype producing a high-acting enzyme may be an independent risk factor for perinatal serotonergic adverse effects after maternal use of SSRIs in late pregnancy.
40 Davidson et al., 2009 Paroxetine, fluoxetine, and citalopram Infants in the SSRI group compared to infants in the control group had <10th percentile birth weight (p<0.045) and head circumference (p<0.04), decreased cortisol (p<0.03) and increased TSH (p<0.004). Infants in the citalopram group showed a lower cord blood IGF-1 compared to paroxetine (p<0.001) and compared to control (p<0.003) groups.
41 Rampono et al., 2009 SSRI and SNRI Cord/Maternal (D/M) distribution ratio of drug concentration: citalopram, escitalopram, fluoxetine, and fluvoxamine and their metabolites were high (median C/M range 0.7-0.86). The Brazelton Neonatal Behavioral Assessments scale (BNBAS) revealed less optimal functioning in the SSRI group compared to controls in habituation, social-interactive, motor, and autonomic clusters (p<0.05). SSRI compared to SNRI groups showed the major decreases in functioning were in the motor and autonomic clusters (p<0.05).
42 O’Brien et al., 2010 Citalopram, Venlafaxine, Fluoxetine, and Sertraline The mean ratio of citalopram (norcitalopram) in the first trimester (p= 0.022) and third trimester ratios (p=0.048) increased significantly compared to the  postpartum period.
43 Colvin et al., 2011 SSRI There was an increased risk of preterm birth after maternal use of any SSRI (OR, 1.43; 95% CI, 1.24-1.65). There was an increased  risk of patent ductus arteriosus (PDA) seen with the use of citalopram (n=5, OR, 5.5; 95% CI, 2.3-13.6) or fluoxetine (n<5; OR, 5.9; 95% CI, 1.5-24.0). In the SSRI group an increased risk of cardiovascular defects (OR, 1.6; 95% CI, 1.1-2.3), cystic kidney disease (OR, 2.8; 95% CI, 1.1-7.0), and lower limb anomalies (OR, 4.2; 95% CI, 1.3-13.9). First trimester administration of citalopram showed increased risk of vesicoureteric reflux (n=5; OR, 3.1; 95% CI, 1.3-7.6) and other anomalies of the lower limbs (n<5; OR, 9.8; 95% CI, 2.3-41.4). Increased risk anomalies of the pulmonary arteries (OR 19.9; 95% CI, 6.0-66.2), other anomalies of the peripheral vascular system (OR, 10.4; 95% CI, 2.5-43.4), and cystic kidney disease (OR, 5.4; 95% CI, 1.3-22.2). There was an increased risk of congenital hypertrophic pyloric stenosis with fluoxetine (OR, 5.4; 95% CI, 1.3-21.9).
44 Malm et al., 2011 SSRI Citalopram was associated with neural tube defects (adjusted OR, 2.46; 95% CI 1.20-5.07). Fluoxetine was associated with all major cardiovascular defects (OR, 1.4; 95% CI, 1.01-1.95) and isolated ventricular septal defects (OR, 2.03; 95% CI, 1.28-3.21). Paroxetine was associated with right ventricular outflow tract defects (adjusted OR, 4.68; 95% CI, 1.48-14.74). Neonates exposed to SSRIs had an increased prevalence of being diagnosed with fetal alcohol spectrum disorders (prevalence 1.2 of 10,000; OR 9.6, 95% CI 4.6-20.0) of nearly 10 fold increase prevalence.
45 Panchaud et al., 2011 Fluoxetine The model-generated estimate of the milk-to plasma ratio for fluoxetine (mean 0.59). The median infant-to-mother ratio of fluoxetine steady state plasma concentrations predicted by the simulation was 8.5%.
46 Alwan et al., 2010 Bupropion The left outflow tract heart defect in exposed infants was (AOR, 2.6; 95% CI, 1.2-5.7) based on 10 exposed pregnancies. The main diagnosis was coarctation of the aorta (AOR, 2.6; 95% CI, 1.0-6.9) in 5 exposed pregnancies. Two of the 10 mothers reported use of antidepressants (fluoxetine and paroxetine in one case and sertraline in the other case) in the first trimester reducing the statistical significance to (AOR, 2.6; 95% CI, 1.0-6.4).
47 Salvatore, stefania, & Cesario, 2011 Aripiprazole One case study of 36 year old women using 10mg/day Aripiprazole at 14 week gestation. No abnormalities noted in infant at 8 weeks after delivery to present.
48 Watanabe et al., 2010 Aripiprazole One case study of 31 year old women using 6mg/day at 22 weeks gestation, 12 mg/day at 30 weeks, and up to 18mg/day at 34 weeks gestation throughout the end of pregnancy. Normal outcomes at 2 months after delivery.
49 Duran et al., 2008 Clozapine Two case studies one used 200mg/day throughout pregnancy and had a normal and healthy baby. The second case study took 200mg/day throughout pregnancy as well and delivered twins in an uncomplicated vaginal delivery.
50 Lutz et al., 2010 Aripiprazole One case study 15mg/day throughout pregnancy. Delivered a normal infant with normal growth at 3 month follow up. Maternal day three and day 27 breast milk collected and aripiprazole and dehydroaripiprazole were not detected. Milk/plasma ratio (<0.04). Relative infant dose from formula evaluation was (<0.7%)
51 Bilad et al., 2011 Olanzapine Neonatal symptoms were seen in eight of 30 (27%) of olanzapine-exposed infants versus one of 51 (2%) of control infants (p=0.001) including symptoms of respiratory distress (2), hypotonia (1), poor sucking or feeding difficulty (2), and a withdrawal syndrome (3). Length of pregnancy was the shortest in the olanzapine non-breastfed group 37.6 (3.1), compared to acetaminophen breastfed 39.6 (1.3) (p=0.003). There were no long-term effects in infants.
52 Vinten et al., 2009 Sodium valproate Children exposed to valproate mono or polytherapy had the lowest adjusted mean scores on tasks relating to daily living and socialization skills. Children exposed to polytherapy with VPA had the lowest adjusted mean scores for communication.
53 Titze et al., 2008 Antiepileptic drugs (AEDs) Adolescent offspring of mothers treated with a single AED only had IQ scores that were only slightly lower than controls (F=4.77; p=0.032). Learning disability (IQ<70) was diagnosed in the polytherapy group nearly six times more frequently than would be expected in the normal population. All AEDs, except carbamazepine, seemed to have a negative impact on adolescents’ total IQ, particularly primidone and valproic acid (mono- and polytherapy).
54 Diav-Citrin et al., 2008 Valproate There was an almost 3-fold increase rate of major anomalies in valproate group compared to controls after exclusion of pregnancies not exposed in the first trimester and of genetic or cytogenetic anomalies (RR=2.66; 95% CI, 1.25, 5.65). There was a 4-fold increase rate of major anomalies in subgroup treated with polytherapy compared to control group (RR=4.07; 95% CI, 1.65, 10.01). Rate of major anomalies was even more pronounced among subgroup treated with a daily valproate dose >1,000mg compared to control group (RR=8.72; 95% CI, 4.16, 18.30). Seven of the eight fetuses or infants with major anomalies were born to mothers who had been taking a daily dose of valproate >1000mg. Cardiovascular anomalies between groups had a 6-fold increase in risk with valproate exposure (5 of 120 [4.2%] vs 8 of 1236 [0.6%]; p=0.004, RR=6.44; 95% CI, 2.14, 19.37).
55 Gentile, 2008 Escitalopram and Alprazolam One case study treated with 40mg/day escitalopram and 1.5mg/day alprazolam had no fetal anomalies and no signs of developmental delay at 6 months follow up.
56 Pawluski et al., 2011 SSRI There were lower APGAR scores at 1 minute for infants with prenatal SSRI exposure (p=0.004) and frequency of jitteriness within first 48 hours after birth. Cord S100B levels among prenatally SSRI-exposed neonates were significantly lower than those among non-exposed neonates (p=0.036) after controlling for third trimester maternal mood and gestational age at birth. SSRI exposure increased S100B in mothers and decreased S100B in neonates.