The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Participants
Total | No-Exposureb | Depressionc | SSRId | SSRI Plus Benzodiazepinee | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Variable | N | % | N | % | N | % | N | % | N | % |
Total enrolled/met eligibility criteria in pregnancy | 243 | 86 | 78 | 65 | 14 | |||||
Withdrew, lost to follow-up, or moved before delivery | 17 | 8 | 4 | 5 | 0 | |||||
Anxiety disorder diagnosis only | 4 | 4 | 0 | 0 | 0 | |||||
Other psychiatric medication without SSRI medication | 18 | 6 | 12 | 0 | 0 | |||||
Total eligible through pregnancy (N; % of enrolled) | 204 | 84.0 | 68 | 79.1 | 62 | 79.5 | 60 | 92.3 | 14 | 100.0f |
Preterm birth (N; % of eligible at birth) | 20 | 9.8 | 2 | 2.9 | 6 | 9.7 | 8 | 13.3 | 4 | 28.6g |
Final sample eligible for standardized newborn assessment (N; % enrolled) | 184 | 90.2 | 66 | 97.1 | 56 | 90.3 | 52 | 86.7 | 10 | 71.4 |
Completed all five assessments (N; % of eligible) | 104 | 56.5 | 39 | 59.1 | 31 | 55.4 | 29 | 55.8 | 5 | 50.0 |
Completed 2–4 assessments (N; % of eligible) | 70 | 38.0 | 25 | 37.9 | 19 | 33.9 | 23 | 44.2 | 3 | 30.0 |
Completed one assessment (N; % of eligible) | 10 | 5.4 | 2 | 3.0 | 6 | 10.7 | 0 | 0.0 | 2 | 20.0 |
Measures
Depression and Antidepressant Group Classification
Infant Measures
Statistical Analyses
Results
Demographic Characteristics
Characteristic | Total (N=184) | A: No Exposure (N=66)a | B: Depression (N=56)b | C: SSRI (N=52)c | D: SSRI Plus Benzodiazepine (N=10)d | Test Statistice | Pairwise Comparisonsf | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mothers | |||||||||||||
Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | F | p | ||
Maternal age (years) | 28.3 | 5.9 | 27.3 | 5.9 | 27.1 | 6.0 | 30.4 | 5.1 | 30.8 | 4.9 | 4.44 | 0.005 | C>A** & B** |
Number of pregnancies | 2.3 | 1.5 | 1.9 | 1.1 | 2.4 | 1.4 | 2.6 | 1.4 | 4.1 | 2.3 | 8.57 | 0.001 | A<C* & D***; D>B*** & C** |
Number of living children | 0.8 | 1.1 | 0.5 | 0.7 | 0.9 | 1.2 | 1.0 | 0.9 | 1.9 | 1.9 | 6.27 | 0.001 | A<C* & D***; D>B*** & C* |
Maternal body mass index prepregnancyg | 27.0 | 6.4 | 25.5 | 6.2 | 27.2 | 6.5 | 28.2 | 6.3 | 29.9 | 6.1 | 2.48 | 0.063 | |
Gestational weeks at first prenatal visith | 7.8 | 3.4 | 8.1 | 3.9 | 7.6 | 3.9 | 7.6 | 2.5 | 7.1 | 3.0 | 0.38 | 0.765 | |
Anxiety severity-pregnancyi | 10.0 | 7.2 | 4.8 | 3.2 | 11.6 | 5.8 | 14.0 | 8.4 | 15.4 | 7.3 | 27.09 | 0.001 | B, C, & D>A***; B=C=D |
Depression severity-pregnancyj | 18.7 | 9.8 | 11.9 | 4.7 | 22.9 | 7.7 | 21.1 | 9.9 | 28.7 | 16.7 | 26.29 | 0.001 | B, C, & D>A***; D>C**; B=C & D |
Depression severity-pospartumj | 12.6 | 9.8 | 7.4 | 4.3 | 14.6 | 7.7 | 15.3 | 11.0 | 24.8 | 19.3 | 15.91 | 0.001 | B, C, & D>A***; D>B** & C** |
N | % | N | % | N | % | N | % | N | % | χ2 | p | ||
Depression severity categoryj | |||||||||||||
None | 74 | 40.4 | 50 | 75.8 | 5 | 8.9 | 17 | 33.3 | 2 | 20.0 | 42.46 | 0.001 | B, C, & D>A***; B=C=D |
Mild | 69 | 37.7 | 16 | 24.2 | 30 | 53.6 | 21 | 40.4 | 3 | 30.0 | |||
Moderate | 32 | 17.5 | 0 | 0.0 | 19 | 33.9 | 12 | 23.5 | 1 | 10.0 | |||
Severe | 8 | 4.4 | 0 | 0.0 | 2 | 3.6 | 2 | 3.9 | 4 | 40.0 | |||
Any anxiety disorder | 48 | 26.1 | 0 | 0.0 | 15 | 26.8 | 23 | 44.2 | 10 | 100 | 16.11 | 0.001 | D>B*** & C*** |
Not married | 83 | 45.9 | 25 | 37.9 | 34 | 64.2 | 18 | 34.6 | 6 | 60.0 | 11.68 | 0.008 | B>A* & C* |
Ethnicity | |||||||||||||
Hispanic | 57 | 31.0 | 24 | 36.4 | 26 | 46.4 | 4 | 7.7 | 3 | 30.0 | 16.17 | 0.001 | C<A*** & B*** |
Non-Whitek | 59 | 33.0 | 25 | 38.5 | 21 | 40.4 | 11 | 21.2 | 2 | 20.0 | 6.04 | 0.110 | |
Lowest socioeconomic status on Hollingshead Four-Factor Indexl | 28 | 15.8 | 9 | 13.6 | 11 | 21.2 | 6 | 12.0 | 2 | 22.2 | 2.13 | 0.546 | |
Infants | |||||||||||||
Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | F | p | ||
Birth weight (grams) | 3.4 | 0.5 | 3.6 | 0.6 | 3.4 | 0.4 | 3.4 | 0.5 | 3.3 | 0.3 | 2.22 | 0.088 | |
Gestational age at birth (weeks) | 39.4 | 1.0 | 39.5 | 1.1 | 39.5 | 0.9 | 39.3 | 1.1 | 38.6 | 0.7 | 2.58 | 0.055 | |
N | % | N | % | N | % | N | % | N | % | χ2 | p | ||
Male | 89 | 48.4 | 36 | 54.5 | 26 | 46.4 | 23 | 44.2 | 4 | 40.0 | 1.72 | 0.632 | |
5-Minute Apgar score <9 | 20 | 10.9 | 6 | 9.1 | 6 | 10.7 | 7 | 13.5 | 1 | 10.0 | 0.52 | 0.914 | |
Cesarean section delivery | 54 | 29.3 | 16 | 24.2 | 18 | 32.1 | 18 | 34.6 | 2 | 20.0 | 2.13 | 0.545 | |
Neonatal intensive care unit admission | 13 | 7.1 | 4 | 6.1 | 1 | 1.8 | 6 | 11.5 | 2 | 20.0 | 5.15 | 0.161 | |
Respiratory distress | 10 | 5.4 | 4 | 6.1 | 1 | 1.8 | 4 | 7.7 | 1 | 10.0 | 1.96 | 0.581 | |
Breastfeeding at birth | 138 | 75.2 | 56 | 85.7 | 41 | 73.5 | 35 | 67.4 | 6 | 60.0 | 5.84 | 0.120 |
Birth Outcomes
Prenatal SSRI Use
Variable | SSRI (N=52) | SSRI Plus Benzodiazepine (N=10) | ||
---|---|---|---|---|
Mean | SD | Mean | SD | |
Mean daily standard dose equivalent SSRIb | 1.7 | 1.0 | 1.7 | 0.9 |
Days of SSRI use in pregnancy | 189.7 | 90.6 | 167.3 | 85.3 |
Days of SSRI use in the first postnatal month | 19.5 | 12.4 | 27.0 | 1.1 |
Maternal plasma SSRI level at delivery (ng/ml)c | 21.4 | 24.3 | 29.6 | 17.7 |
Infant cord blood SSRI level at delivery (ng/ml)d | 12.3 | 9.9 | 7.3 | 4.4 |
N | % | N | % | |
Number using SSRIs in the first trimester | 39 | 75.0 | 5 | 50.0 |
Number using SSRIs in the second trimester | 44 | 86.6 | 8 | 80.0 |
Number using SSRIs in the third trimester | 41 | 78.9 | 9 | 90.0 |
Number using SSRIs in the first postnatal month | 41 | 78.9 | 10 | 100.0 |
Primary SSRI Taken | ||||
Sertraline | 32 | 61.5 | 6 | 60.0 |
Citalopram | 7 | 13.5 | 3 | 30.0 |
Escitalopram | 3 | 5.8 | 0 | |
Fluoxetine | 5 | 9.6 | 1 | 10.0 |
Venlafaxine | 4 | 7.7 | 0 | |
Duloxetine | 1 | 1.9 | 0 | |
Benzodiazepine use in pregnancy | ||||
Benzodiazepine use through delivery | 0 | 9 | 90.0 | |
Benzodiazepine use in the first postnatal month | 0 | 8 | 80.0 | |
Clonazepam | 0 | 2 | 20.0 | |
Lorazepam | 0 | 6 | 60.0 | |
Alprazolam | 0 | 2 | 20.0 | |
Other concurrent medications | ||||
Atypical antidepressant (bupropion) | 3 | 5.8 | 3 | 30.0 |
Hypnotic antidepressant (trazodone, amitriptyline) | 6 | 11.5 | 1 | 10.0 |
Hypnotic, non-benzodiazepine | 5 | 9.6 | 3 | 30.0 |
Buspirone | 0 | 1 | 10.0 | |
Melatonin | 1 | 1.9 | 0 | |
Hydroxyzine | 0 | 1 | 10.0 | |
Zolpidem tartrate | 4 | 7.7 | 1 | 10.0 |
Atypical antipsychotic (quetiapine) | 1 | 1.9 | 0 |
Main Effects of Exposure Group on Newborn Neurobehavior
Variable | Group Main Effect | Model 3 Group-Estimated Means (Standard Errors) | Comparison Tests for Significant Modelsh | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Model 1 | Model 2 | Model 3 | A | B | C | D | |||||||||
Unadjusteda | Adjustedb | Adjusted Plusc | No Exposured | Depressione | SSRIf | SSRI Plus Benzodiazepineg | |||||||||
χ2 | p | χ2 | p | χ2 | p | Mean | SE | Mean | SE | Mean | SE | Mean | SE | ||
Arousal | 1.30 | 0.729 | 0.83 | 0.841 | 11.06 | 0.011 | 4.19 | 0.10 | 4.00 | 0.07 | 4.09 | 0.07 | 4.19 | 0.20 | None |
Excitability | 2.43 | 0.488 | 1.94 | 0.586 | 7.33 | 0.062 | 3.98 | 0.34 | 3.72 | 0.25 | 4.11 | 0.23 | 5.00 | 0.68 | |
Handling | 1.05 | 0.790 | 0.74 | 0.865 | 0.33 | 0.954 | 0.36 | 0.04 | 0.35 | 0.03 | 0.36 | 0.03 | 0.39 | 0.08 | |
Self-regulation | 3.00 | 0.392 | 2.72 | 0.438 | 4.55 | 0.208 | 5.30 | 0.13 | 5.49 | 0.09 | 5.29 | 0.09 | 5.00 | 0.25 | |
Quality of movement | 26.49 | <0.0001 | 25.16 | <0.0001 | 12.41 | 0.006 | 4.30 | 0.09 | 4.22 | 0.06 | 4.04 | 0.06 | 3.67 | 0.17 | A>C* & D**; B>C* & D** |
Stress-abstinence signs | |||||||||||||||
CNS | 11.27 | 0.010 | 14.01 | 0.003 | 9.19 | 0.027 | 0.19 | 0.02 | 0.19 | 0.01 | 0.23 | 0.01 | 0.27 | 0.03 | A<C* & D*; B<C** & D* |
Total | 4.79 | 0.188 | 3.86 | 0.278 | 5.92 | 0.116 | 0.16 | 0.01 | 0.15 | 0.01 | 0.17 | 0.01 | 0.16 | 0.02 | |
Hypertonia | 2.13 | 0.545 | 3.03 | 0.388 | 2.35 | 0.503 | 0.44 | 0.11 | 0.44 | 0.08 | 0.31 | 0.08 | 0.32 | 0.23 | |
Hypotonia | 10.52 | 0.015 | 11.59 | 0.009 | 4.94 | 0.176 | 0.27 | 0.08 | 0.31 | 0.06 | 0.51 | 0.05 | 0.46 | 0.16 | Model 2: C>A** & B* |
Lethargy | 6.47 | 0.091 | 5.00 | 0.172 | 3.22 | 0.358 | 4.74 | 0.30 | 5.00 | 0.23 | 5.03 | 0.21 | 5.99 | 0.61 | |
Attention | 6.44 | 0.092 | 4.63 | 0.201 | 3.59 | 0.309 | 4.95 | 0.19 | 4.84 | 0.14 | 4.79 | 0.13 | 4.09 | 0.42 | |
Habituation | 10.63 | 0.014 | 10.22 | 0.017 | 2.22 | 0.528 | 7.69 | 0.50 | 7.02 | 0.34 | 6.94 | 0.30 | 6.85 | 0.68 | Model 2: A>B* & C** |
Non-optimal reflexes | 5.76 | 0.124 | 5.87 | 0.118 | 1.53 | 0.675 | 4.27 | 0.26 | 4.53 | 0.20 | 4.76 | 0.18 | 4.95 | 0.54 | |
Asymmetry | 1.70 | 0.636 | 1.87 | 0.601 | 1.73 | 0.630 | 0.92 | 0.15 | 0.95 | 0.12 | 1.17 | 0.11 | 1.16 | 0.32 |
Main Effects of Days From Birth at Infant Neurobehavioral Assessment
Group-by-Day Interactions
Discussion
Limitations
Conclusions and Implications for Clinical Practice
Acknowledgments
Supplementary Material
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