Supplemental Material: Case series and reports of exposure to antidepressants and anxiolytic medication and neurodevelopmental outcomes
Case series
Study
Medication
studied
Child characteristics
Findings reported
Stiskal et al., 2001
SSRI
Nordeng et al.,
2001
SSRI
All four neonates showed some withdrawal. The symptoms and abnormalities included, but were not limited to,
jitteriness, vomiting, irritability, hypoglycemia and necrotizing enterocolitis [1].
All children showed withdrawal symptoms within a few days after birth that lasted up to one month after birth.
Symptoms were irritability, crying, jitteriness, increased tonus, eating and sleeping difficulties and convulsions [2].
Troutman &
Momany, 2012
SSRI, one child
exposed to SSRI
+ bupropion
4 neonates born at 37-38
weeks
5 neonates, all boys born
at term, but one child was
born at 27th week of
gestation
5 infants (2 girls, 3 boys)
aged ~1 year
Medication
studied
Child characteristics
Findings reported
Santos and
Pergolizzi, 2004
Anbu and
Theodore, 2006
Ahmed et al., 2007
SSRI
Boy, born at 38 weeks
SSRI
Girl, born at term
SSRI
Boy, born at term
Marsella et al.,
2010
SSRI
Two girls, monozygotic
twins born at 33 weeks of
gestation
Farra et al., 2010
SSRI
Boy, born at 39 weeks
Pogliani et al.,
2010
Jaiswal et al., 2003
SSRI
Boy, born at 38 weeks of
gestation
Boy, born at term
Physical examination was normal, but neurological symptoms in the first 3 days were: jitteriness, exaggerated Moro
response, deep and brisk tendon reflexes, a marked startle response. Sertraline was present in the child’s plasma [4].
Jitteriness, hypertonia, sneezing, fever, vomiting and poor feeding. Tonus was increased in all four limbs. Child was
diagnosed with fluoxetine withdrawal syndrome. Jitteriness resolved after one week [5].
Child was born floppy, required resuscitation, had spasms. Tonic convulsions at birth, which continued intermittently
until 48 hours after birth. He had hypertonia, hypoglycemia and respiratory distress (paroxetine withdrawal) [6].
Abnormalities at ultrasound 20 weeks: right aortic arch in first twin and single umbilical artery in second twin. At
birth, cardiorespiratory problems, facial dysmorphisms, neurobehavioral and motor signs in both twins. At discharge
(3 months) the first twin presented hypertonia and the second twin a hypotonic syndrome with mild delay in motor
development. At follow-up (6 months), the twins showed an adequate psychomotor development [7].
At birth, newborn was cyanotic, and hypoglemic. Severe physical, cardiac, skeletal and ophthalmic abnormalities
were observed. The child was diagnosed with Goldenhar syndrome [8].
Neonatal withdrawal syndrome symptoms persisted 5 days, EEG and diffusion weighted MRI 3 hours after birth
were normal, blood glucose was normal, no infections, seizure-like movements presented at 6 hours of life [9].
At birth, the child required oxygen ventilation and hypertonia and opisthotonus. The infant developed profuse
salivation and marked jitteriness, with improvement on day 3. At follow-up, the infant was normal [10].
Case reports
Study
Hadded et al.,
2005
Eyal and Yaeger,
SSRI + antiepileptic
medication
SSRI + antiepileptic
medication
SNRI
Four of five infant-mother dyads were classified on disorganized with the strange situation procedure [3].
Girl, born at 39 weeks
The infant displayed respiratory distress, jitteriness, tremor, jerking movements, hypertonia, and hyperreflexia. The
diagnosis was serotonin syndrome. At follow-up, neurodevelopment was normal [11].
Girl, born at 38 weeks.
At birth, the child had respiratory problems and low oxygen saturation. On day 3, she developed ‘jerky rhythmic
2008
Hoppenbrouwers
et al., 2010
SNRI
Boy, born at 41 weeks of
gestation
Frey et al., 1999
TCA (pregnancy
and postpartum)
Boy, born at term
Bloem et al., 1999
TCA
Boy, born at term
Sokolover et al.,
2008
TCA
Alehan et al., 2008
Benzodiazepine
(first trimester) +
SSRI (second
and third
trimester)
Twins, boys,
monozygotic, born at 35
weeks
Girl, born at 41 weeks
movements’. EEG showed nonspecific encephalopathic finding. The child was diagnosed with tremors and neonatal
seizures associated with neonatal behavior syndrome. At 2 years, the child was healthy with normal neurobehavioral
development [12].
The child had tachypnea, feeding difficulties, mild withdrawal, and a neonatal infection. Restlessness, tachypnea,
higher Finnegan scores, and episodes of extensor limb posturing and severe agitation were observed. EEG results
were judged as ‘suspect for epilepsy’ [13].
At 9 days the infant showed poor sucking, swallowing problems, muscle hypotonia, and vomiting. He had lost
weight, was drowsy and jaundiced. Breastfeeding was discontinued, because doxepin was detected in breast milk and
in the child’s plasma. Two days later he was asymptomatic and was discharged [14].
Two days after birth the child was jittery and showed startling impulses, simultaneous and symmetrical jerks of arms
and legs. The jerks could be provoked by touch or auditory stimuli, and stopped by briefly stabilizing the limb.
Ultrasound brain scans and EEG were normal. The diagnosis was a generalized, stimulus sensitive, status myoclonus.
Examination three weeks later was normal, except for mild jitteriness in response to touch [15].
At birth, mild hypotonicity and poor sucking were noted in one twin, but physical and neurological examinations
were normal. On day 3, both twins showed hypothermia, and thermal instability until the 10 th day of their life.
Follow-up at 4 months showed normal growth and development [16].
Infant was jittery, hypertonic with oculogyric crises, vomited and showed poor feeding. The child was diagnosed
with fluoxetine withdrawal, which persisted for 6 weeks. At 3 years old, the child had mild mental retardation and
microcephaly [17].
Abbreviations: EEG: electroencephalogram; MAO: monoamine oxidase inhibitor; MRI: magnetic resonance imaging; NDRI: norepinephrine/dopamine
reuptake inhibitor; SNRI: serotonin/norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant.
References:
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17.
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