Early-Life Predictors of Fetal Alcohol Spectrum Disorders

Abstract

Background and objectives: Fetal alcohol spectrum disorders (FASD) comprise the continuum of disabilities associated with prenatal alcohol exposure. Although infancy remains the most effective time for initiation of intervention services, current diagnostic schemes demonstrate the greatest confidence, accuracy, and reliability in school-aged children. Our aims for the current study were to identify growth, dysmorphology, and neurodevelopmental features in infants that were most predictive of FASD at age 5, thereby improving the timeliness of diagnoses.

Methods: A cohort of pregnant South African women attending primary health care clinics or giving birth in provincial hospitals was enrolled in the project. Children were followed longitudinally from birth to 60 months to determine their physical and developmental trajectories (N = 155). Standardized protocols were used to assess growth, dysmorphology, and development at 6 weeks and at 9, 18, 42, and 60 months. A structured maternal interview, including estimation of prenatal alcohol intake, was administered at 42 or 60 months.

Results: Growth restriction and total dysmorphology scores differentiated among children with and without FASD as early as 9 months (area under the receiver operating characteristic curve = 0.777; P < .001; 95% confidence interval: 0.705-0.849), although children who were severely affected could be identified earlier. Assessment of developmental milestones revealed significant developmental differences emerging among children with and without FASD between 18 and 42 months. Mothers of children with FASD were significantly smaller, with lower BMIs and higher alcohol intake during pregnancy, than mothers of children without FASD.

Conclusions: Assessment of a combination of growth, dysmorphology, and neurobehavioral characteristics allows for accurate identification of most children with FASD as early as 9 to 18 months.

FIGURE 1

Consolidated Standards of Reporting Trials chart for the longitudinal study. ^aAfter 44 subjects were excluded because of incomplete data, 155 children completed the entire battery.

FIGURE 2

Weight, OFC, and total dysmorphology score over time.

FIGURE 3

ROC analysis: AUC for accuracy of the total dysmorphology score in discriminating children with FASD from children without FASD at T2 (9 months of age) evaluation.

FIGURE 4

Total dysmorphology score over time by diagnosis at 60 months (5 years); error bars: ± 1 SE; N = 94 (total number of children seen at all 5 time points); repeated measures analysis, within subjects effect, time: F = 24.263, P < .001; repeated measures analysis, within subjects effect, time × group: F = 2.370, P < .002; repeated measures analysis, between subjects effect, group: F = 21.338, P < .001; Mauchly’s test of Sphericity has been violated: χ²(9) = 17.118, P = .047.

FIGURE 5

Cognitive percentile scores over time; error bars: ± 1 SE; the BSID-III was used in T1 to T4; the KABC-II was used in T5; N = 57 (total number of children seen at all 4 time points); repeated measures analysis, within subjects effect, time: F = 8.687, P < .001; repeated measures analysis, within subjects effect, time × group: F = 1.340, P = .198; repeated measures analysis, between subjects effect, group: F = 0.174, P = .971; Mauchly’s test of Sphericity has been violated: χ²(5) = 22.736, P < .001.