Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors
Neonatology 2013;104:65-70
Alexis Ireland, PharmD Candidate 2014
Background
· Usage of antidepressant medications has increased in entire population, especially in pregnant women
· SRI medications have been considered safe in pregnancy due to large therapeutic range and fewer side effects when compared to other antidepressants
· Little research has been done on effect on fetus/neonate and extent of observation and follow-up required
· Some risks found include premature delivery, low birth weight, meconium-stained amniotic fluid, low Apgar score, respiratory distress, pulmonary hypertension, hypoglycemia, convulsions, neonatal abstinence syndrome (central nervous system, gastrointestinal system, and autonomic nervous system), and NICU admission
· Symptoms present in 28-30% of exposed infants in referenced studies
· Intense monitoring of newborn deprives mother and baby of bonding time and may be unnecessary
Objectives
· Evaluate short-term neonatal symptoms related to in utero exposure to SRI medications to determine level of monitoring and observation necessary due to symptom severity and duration
Study Design & Methods
· Retrospective review of medical charts of term infants born to mothers who self-reported SRI use during pregnancy up to delivery
· Matched control born at same gestational age and born closest in time to study infants
· Sheba Medical Center in Israel from Jan 2007-Dec 2011
· Infants taken to secondary-level care unit for 48 hours after birth
· Nurses monitored vital signs, temperature, capillary glucose, NAS scores, and symptoms every 8 hours
· Symptoms charted included convulsions, jitteriness, sleepiness, restlessness, tachycardia, bradycardia, tachypnea, cyanotic events, feeding difficulties, regurgitations, and vomiting
· Significant symptoms included respiratory distress lasting longer than 6 hours, convulsions, cyanotic events, or fever ≥38°C as well as combination of two mild symptoms (sleepiness/restlessness, jitteriness, feeding difficulties)
· Exclusion criteria: preterm infants, in utero exposure to psychiatric medications, B-blockers, alcohol, or illicit drugs
· Maternal data collected: diseases (hypothyroidism, hypertension, gestational diabetes), GBS status, prolonged rupture of membranes, meconium-stained amniotic fluid, delivery mode, and type/dose SRI used
· High dose: fluoxetine/paroxetine/citalopram dose 40 mg/day or higher; sertraline/fluvoxamine/ venlafaxine dose 150 mg/day or higher
· Infant data collected: gestational age, birth weight, weight for gestational age, length, head circumference, gender, Apgar at 1 and 5, congenital malformations, respiratory distress syndrome, usage/duration of oxygen, antibiotic use, cardiac anomalies, hypoglycemia, length of stay
· Same demographic and clinical data collected for control infants but vital signs and glucose monitoring was only as indicated by postnatal course
Statistical Analyses
· Continuous variables were compared using analysis of variance
· Categorical variables were compared using Pearson’s x2 test or Fisher’s exact test
· P value of <0.05 considered significant
· Analyses performed using SPSS version 15 software
Results
· 38,036 term infants born, 452 infants exposed to SRI in utero, 401 infants included in study group
· More infants in study group were born to diabetic mothers (p=0.028), shorter in length (p=0.023), low Apgar score <7 at 1 minute (p=0.002), meconium-stained amniotic fluid (p<0.001), and respiratory distress syndrome (0.026)
· After excluding respiratory distress syndrome, onset of symptoms was 29 hrs (5-48 hrs)
Symptom
|
Number
|
Percent
|
One symptom
|
165
|
41%
|
RDS
|
19
|
5%
|
Jitteriness
|
53
|
13%
|
Restlessness
|
33
|
8%
|
Feeding Difficulties
|
17
|
4%
|
Regurgitations
|
79
|
20%
|
Fever
|
2
|
0.5%
|
Short Cyanotic Event
|
3
|
0.75%
|
Convulsions
|
1
|
0.25%
|
Significant Symptom
|
Study
|
Control
|
One significant symptom
|
46 (11%)
|
10 (2.5%)
|
RDS longer than 6 hours
|
12 (3%)
|
7 (2%)
|
Convulsions
|
1 (0.25%)
|
1 (0.25%)
|
Short Cyanotic Events
|
3 (0.75%)
|
2 (0.5%)
|
Fever
|
2 (0.5%)
|
Not reported
|
Two mild symptoms
|
24 (6%)
|
Not reported
|
Three mild symptoms
|
4 (1%)
|
Not reported
|
· Study group: NICU admissions due to low Apgar, malrotation, and exchange transfusion
· Control group: NICU admissions due to respiratory distress, convulsions, and exchange transfusion
· High-SRI dose: MSAF (p<0.001), low Apgar at 1 (p=0.007), regurgitation (p=0.043)
· Comparison between subgroups of medications limited due to high variance of use
Author’s Conclusions
· High rate of symptoms recorded could be due to close observation of infants (all minor clinical manifestations reported)
· Most infants presented with mild symptoms, all with non-life-threatening symptoms, which could be monitored in rooming-in setting with subsequent admission to secondary-level care unit if warranted
· Monitoring by parents or care staff should continue for 48 hours after birth
· NICU admissions were not likely related to SRI exposure and were similar to admissions in the control group
· Possible intrauterine fetal stress with SRI exposure depressing HPA axis leading to relaxation of anal sphincter and meconium excretion which results in meconium-stained amniotic fluid and low Apgar at 1 minute. No meconium aspiration noted in study or control group. Stress was mild because all Apgar’s were normal at 5 minutes.
· Higher incidence of respiratory distress but similar use of oxygen at 6 hours when compared to controls. No NICU admissions due to respiratory distress.
· Conclusion: Infants exposed to SRI in utero do not obligate monitoring involving separation from parents. Parents and clinical staff should be educated on signs to look for and follow-up regarding feeding difficulties and restlessness.
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