Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development.

OBJECTIVES: This study evaluated the question whether length of in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants might affect neonatal outcome and psychomotor development in infancy. METHODS: Birth outcome was determined in the offspring of 55 women with major depressive disorder who used SSRI medication for different durations during their pregnancies. At an average age of 14 months, children underwent a pediatric examination and an evaluation with the Bayley Scales of Infant Development (BSID-II). RESULTS: Duration of in utero exposure to SSRIs was negatively associated with total Apgar scores, specifically the activity subscale. Odds ratios for a low score (<2) on this scale were 3.8 and 6.0 at 1 and 5 min, respectively. Newborns with longer exposure were more often admitted to the Neonatal Intensive Care Unit (p < .03). Mental Development Index scores of the infants were not associated with the length of gestational exposure to SSRIs. A longer duration of exposure increased the risk for lower Psychomotor Developmental Index and Behavioral Rating Scale scores in infancy (p = 0.012 and p = 0.007, respectively) on the BSID-II. CONCLUSIONS: The findings provide evidence that the length of prenatal SSRI antidepressant use can affect neonatal adjustment and can have an effect on psychomotor test scores in infancy. Importantly, the children's mental development and motor function by neurological examination were within the normal range. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations.

Neurobehavioral assessment predicts differential outcome between VLBW and ELBW preterm infants.

OBJECTIVE: To evaluate the impact of birth weight on development of very low birth weight (VLBW) infants using the Neurobehavioral Assessment of the Preterm Infant (NAPI) before hospital discharge, and to show the relation to follow-up outcomes at 12, 18 and 30 months of age. STUDY DESIGN: In total, 113 preterm infants were assessed with the NAPI at 36 weeks postmenstrual age. Later, neurodevelopment was examined using the Bayley Infant Neurodevelopmental Screener (BINS) at 12 months and the Bayley Scales of Infant Development, at 18 and 30 months. The cohort was divided into two groups, based on birth weight, extremely low birth weight (ELBW) (<1000 g) and VLBW (1000 to 1500 g). RESULTS: ELBW infants showed significantly lower NAPI scores compared with VLBW infants at 36 weeks. The predischarge NAPI scores correlated with the 12, 18 and 30 months scores when the ELBW infants continue to have lower performance than the VLBW infants. In all, 14 infants developed cerebral palsy. These infants had significantly lower NAPI, BINS and Bayley scores compared with all other preterm infants. CONCLUSION: NAPI before discharge provides clinically meaningful information related to later neurodevelopmental outcome.

Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants.

OBJECTIVE: To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP). METHODS: Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized as "abnormal." The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination. RESULTS: The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months. CONCLUSIONS: As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.

Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy.

OBJECTIVE: To compare the structural growth and developmental outcome of children born to mothers diagnosed with major depressive disorder during pregnancy who were exposed or not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero. STUDY DESIGN: Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication (n = 13) were compared with children of depressed mothers treated with SSRIs (n = 31) on birth outcomes and postnatal neurodevelopmental functioning between ages 6 and 40 months. Children underwent blinded standardized pediatric and dysmorphology examinations and evaluations of their mental and psychomotor development with the use of the Bayley Scales of Infant Development (BSID II). RESULTS: The Bayley mental developmental indexes were similar in both groups. Children exposed to SSRIs during pregnancy had lower APGAR scores and scored lower on the Bayley psychomotor development indexes and the motor quality factor of the Bayley Behavioral Rating Scale than unexposed children. CONCLUSIONS: The findings that SSRIs during fetal development might have subtle effects on motor development and motor control are consistent with the pharmacologic properties of the drugs.

The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates.

OBJECTIVE: To evaluate the adequacy of newborn hearing screening in the identification of hearing loss in post-neonatal intensive care unit (NICU) infants. METHODS: Eighty-two post-NICU infants who had initially passed automated auditory brainstem response (AABR) screening were studied prospectively between November 1997 and July 1999. Tympanometry and transient evoked otoacoustic emissions (TEOAE) were used to evaluate middle ear status and screen the hearing of subjects when they were seen routinely in the Mary L. Johnson Infant Development Clinic, where NICU graduates are followed at our institution. TEOAEs were not performed in subjects with abnormal tympanometry, defined as negative pressures greater than 200 daPa or flat tympanograms. RESULTS: Of the 82 subjects, 31 (37%) had abnormal tympanometry in at least one ear, with 24 (29%) exhibiting abnormal values bilaterally. Two subjects were identified with delayed-onset or previously undiagnosed sensorineural hearing loss. One had a history of persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation. The other infant had no risk factors for sensorineural hearing loss. CONCLUSIONS: Our data indicate that newborn hearing screening programs may not provide adequate vigilance for NICU graduates. The high incidence of abnormal middle ear status and the identification of delayed-onset hearing loss in an infant without known risk factors highlights the need for close audiologic and speech/language follow-up in the post-NICU population.

Infant heart transplantation at Stanford: growth and neurodevelopmental outcome.

OBJECTIVE: To evaluate the growth and neurodevelopmental outcome of 18 surviving Stanford patients who received heart transplantations before their second birthday. METHODS: We compared the growth and neurodevelopmental outcome of these 18 patients with a second group of age-matched comparison patients who underwent other heart surgery requiring cardiopulmonary bypass. RESULTS: Difficulties with growth and development were more common in the transplant group as were neurologic abnormalities. Speech and language delays as well as hearing problems were also more common in the transplant group. CONCLUSION: Multicenter prospective longitudinal neurodevelopmental outcome studies of infant heart transplant patients should be conducted to provide a more efficient basis for evaluating management protocols and assessment of long-term outcomes and of the need for early intervention services.