Lynn T. Singer

Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

OBJECTIVE Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. METHOD This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. RESULTS Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. CONCLUSIONS For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

Effects of infant risk status and maternal psychological distress on maternal-infant interactions during the first year of life

ABSTRACT. The associations of infant medical risk, prematurity, and maternal psychological distress with the quality of maternal-infant interactions during the first year of life were evaluated in a prospective, longitudinal follow-up from birth. A total of 103 high-risk very low birth weight (VLBW) infants with bronchopulmonary dysplasia, 68 low-risk VLBW infants without bronchopulmonary dysplasia, and 117 healthy term infants were seen at 1, 8, and 12 months of age. Videotaped feedings at each age were rated using the Nursing Child Assessment Feeding Scale, and mothers completed the Brief Symptom Inventory as a measure of psychological distress. VLBW infant status was related to both maternal and infant behaviors as well as to maternal distress, and these relationships varied with infant age. Overall, VLBW infants displayed fewer responsive, clear interactions, with differences from term infants increasing over time. Maternal distress was related to less cognitive growth fostering for all mothers. Because maternal distress is more prevalent in mothers of VLBW infants postpartum, intervention efforts should focus on assessment of maternal distress and the challenges posed by the interactive behaviors of VLBW infants.

Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula

Background In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. Objective To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. Methods The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750–1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050–3,300 kJ/L, 22–24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) ≥ 50% energy from human milk before hospital discharge (≥ 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0–1.5 cm) and had larger head circumferences (0.3–1.1 cm) than both PHM-T and ≥ 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed ≥ 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). Conclusion Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

Relationship of prenatal cocaine exposure and maternal postpartum psychological distress to child developmental outcome

Maternal cocaine use during pregnancy can affect the infant directly through toxic effects or indirectly through cocaines influence on maternal psychological status. We followed 160 cocaine exposed and 56 nonexposed infants and their mothers identified at birth through interview and/or urine screen. Although cocaine exposure defined the groups, infant exposure to alcohol, marijuana, and tobacco was allowed to vary. Infants were 99% African American and poor. All mothers completed the Brief Symptom Inventory (BSI) and infants were given the Bayley Scales of Mental (MDI) and Motor (PDI) Development at a mean corrected age of 17 +/- 8 months. Both MDIs (94 +/- 17 vs. 103 +/- 16) and PDIs (101 +/- 16 vs. 108 +/- 12) were lower for cocaine exposed infants. Psychological distress was greater in cocaine using mothers. Hierarchical multiple regression was used to assess the relative effects of gestational age, maternal psychological distress, and cocaine and polydrug exposure on infant outcomes. Both psychological distress and cocaine and alcohol exposure predicted lower MDIs after controlling for prematurity. Neither psychological distress nor alcohol exposure predicted motor outcome, while cocaine had a significant effect. Tobacco and marijuana exposure were unrelated to outcome. These findings provide further support for direct effects of cocaine and alcohol on infant development as well as highlight the need for studies to document maternal psychological factors, which may increase child risk for poorer outcomes.

Effects of cocaine/polydrug exposure and maternal psychological distress on infant birth outcomes

To assess teratogenic effects of cocaine exposure and maternal psychological distress on birth outcomes, we conducted a longitudinal prospective study of 415 infants (218 cocaine-exposed--CE, 197 nonexposed--NE). Drug exposure was determined through a combination of maternal self-report, urine, and meconium screens. Maternal psychological distress postpartum was evaluated through a standardized, normative, self-report assessment. An extensive set of confounding variables was controlled, including severity of exposure to alcohol, tobacco, marijuana and other drugs, maternal age, race, parity, number of prenatal care visits, educational, marital, and socioeconomic status, and verbal and nonverbal intelligence. CE infants were smaller on all birth parameters and more likely to be preterm, small for gestational age, and microcephalic than NE infants. Forty-one percent of cocaine users had clinically significant psychological symptoms, compared to 20% of a high-risk comparison group of noncocaine users. Consistent with a teratologic model, cocaine exposure independently predicted offspring birthweight, length, and head circumference. Maternal psychological distress self-reported postnatally also independently predicted head circumference. Tobacco, alcohol, and marijuana exposures were also significant independent predictors of some fetal growth parameters. In addition, maternal distress symptoms, which may be reflective of maternal mental health disorders or responses to stress, added significantly to the risk for poorer fetal growth.

Preschool language outcomes of children with history of bronchopulmonary dysplasia and very low birth weight.

A prospective follow-up of very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD) and term control infants was conducted. The effects of BPD and VLBW on speech-language development and specific language impairment at 3 years of age were investigated, controlling for the effects of sociodemographic and other medical risk factors. Groups were compared on cognitive and speech-language outcomes using the Battelle Language and Bayley Mental Scales of Infant Development. Children with a history of BPD had lower receptive language skills than VLBW children without BPD, who in turn had lower receptive skills than term children. Children with a history of BPD also had lower expressive skills than the two comparison groups, whereas VLBW children without BPD did not differ in expressive language from term children. When IQ score was controlled, children with BPD demonstrated specific language impairment in receptive language. The presence of patent ductus arteriosis (PDA) was the best predictor of language deficits and the combined occurrence of PDA and BPD resulted in differentially lower language scores. Neurologic complications, low socioeconomic status, and minority race were also significant predictors of language delay. The findings emphasize the importance of considering both medical and sociodemographic factors in evaluating the risk of VLBW infants for poorer speech-language outcomes.

Neurobehavioral outcomes of cocaine-exposed infants

The present study investigated the neurobehavioral outcomes of fetal cocaine exposure. Attempts were made to control, by design or statistical analysis, for significant confounders. Timing and amount of drug exposures were considered, and biologic measures of exposure were quantified to classify exposure severity. One hundred sixty-one non-cocaine and 158 cocaine-exposed (82 heavily and 76 lightly exposed) infants were seen at a mean-corrected age of 43 weeks post-conception and administered the Neurobehavioral Assessment (NB Assessment). Heavily cocaine-exposed infants had more jitteriness and attentional problems than lightly and non-exposed infants. They also had more movement and tone abnormalities, and sensory asymmetries than non-exposed infants. Heavily exposed infants were more likely to be identified with an abnormality than non-exposed infants and there was a trend toward heavily exposed infants being more likely to be identified with an abnormality than lightly exposed infants. Furthermore, there was a trend for heavily exposed infants to be less likely to be testable than non-exposed infants. After the confounding and mediating factors were considered, heavily cocaine-exposed infants were four times as likely to be jittery and nearly twice as likely to demonstrate any abnormality than lightly and non-exposed infants, but all other effects were no longer significant. Higher concentrations of the cocaine metabolites of cocaine, cocaethylene, and benzoylecgonine (BZE) were related to higher incidence of movement and tone abnormalities, jitteriness, and presence of any abnormality. Higher cocaethylene levels were related to attentional abnormalities and higher meta-hydroxybenzoylecgonine (m-OH-BZE) was related to jitteriness. Drug effects on attention were mediated by maternal psychological distress, suggesting that this factor should be considered in future studies of drug exposure effects.

Motor Development of Cocaine-exposed Children at Age Two Years

Objective. This article was designed to investigate effects of prenatal cocaine exposure on motor development of young children from a predominately underprivileged, urban population. Methodology. A total of 260 infants and young children were initially recruited from either the newborn nursery or the at-risk pediatric clinic of an urban teaching hospital. Prenatal history and birth outcomes were collected from medical records. Demographic characteristics and additional drug histories were obtained from the mothers. The 199 subjects (98 cocaine-exposed and 101 unexposed) who returned at age 2 years were assessed by examiners blinded to drug exposure status using the Peabody Developmental Motor Scales. Results. Compared with control subjects, the cocaine-exposed group performed significantly less well on both the fine and the gross motor development indices. Mean scores for both groups were within the average range on the gross motor index, but greater than 1 standard deviation below average on the fine motor index. Differences were significant on the balance and the receipt and propulsion subscales of the gross motor scale, and on the hand use and the eye–hand coordination subscales of the fine motor scale. Cocaine status independently predicted poorer hand use and eye–hand coordination scores. There also was an effect of alcohol exposure on the receipt and propulsion subscale. Conclusions. Findings indicate that deficiencies in motor development remain detectable at 2 years of age in children exposed to drugs prenatally. Although other environmental variables may influence motor development, children exposed to cocaine and to alcohol in utero may encounter developmental challenges that impede later achievement.

SOCIAL SUPPORT, PSYCHOLOGICAL DISTRESS, AND PARENTING STRAINS IN MOTHERS OF VERY LOW BIRTHWEIGHT INFANTS

This study investigated maternal psychological distress, perceptions of social supports, and parenting strains after the birth of a very low birthweight (VLBW) infant. Compared to mothers of term infants, mothers of VLBW infants had significantly higher incidence of psychological distress during the neonatal period, but did not differ from mothers of term infants in their feelings of role restriction, parenting competence, or social supports. Lower general social support predicted high distress levels, but only for mothers of VLBW infants. Mothers with a low sense of parenting competence, but support from spouse/partners reported lower maternal distress.

Executive Functioning in Preschool‐Age Children Prenatally Exposed to Alcohol, Cocaine, and Marijuana

BACKGROUND Reports from clinical and experimental (animal) research converge on the suggestion that prenatal exposure to alcohol, cocaine, or marijuana undermines executive functioning (EF) and its neurological underpinnings. However, large, adequately controlled, prospective studies of alcohol and marijuana effects on EF have reported conflicting findings, and there have been no such studies of cocaine exposure. METHODS EF was investigated in a cohort (n = 316) of 4-year-old children the majority of whose mothers had used varying combinations of cocaine, alcohol, and marijuana during pregnancy. With use of postpartum maternal report and biological assay, children were assigned to overlapping prenatal cocaine-exposed, alcohol-exposed, and marijuana-exposed groups and to complementary control groups. The postnatal environmental assessment included measures of maternal intellectual and psychosocial functioning, current drug or alcohol use, and home environment. RESULTS The children in the alcohol-exposed group had worse tapping-inhibition performance than children in the non-alcohol-exposed group, and this effect persisted when potential confounding environmental variables, other drug variables, and concurrent verbal intelligence were controlled for. CONCLUSIONS Prenatal alcohol is predictive of decreased EF in early childhood that could not be attributed to environmental factors. The results are discussed in terms of the age and overall high-risk status of the children.