Background Pregnant women participated in multifaceted case management (MCM) to prevent Fetal Alcohol Spectrum Disorders (FASD). Methods Women recruited from antenatal clinics for a longitudinal child development study were screened for alcohol use. Forty-four pregnant women were defined as high-risk drinkers on the Alcohol Use Disorder Identification Test (AUDIT) by an AUDIT score ≥8 and participated in 18 months of MCM to facilitate reduction or cessation of alcohol consumption. Forty-one women completed MCM. Fifty-five equally high-risk women who received standard antenatal care comprised the comparison/control group. Development in offspring was evaluated by a blinded interdisciplinary team of examiners through 5 years of age. Results At five years of age, more children (34%) of MCM participating women did not meet the criteria for FASD vs. non-MCM offspring (22%). Furthermore, a statistically significant (p = .01) lower proportion of MCM offspring (24%) was diagnosed with fetal alcohol syndrome (FAS) compared to controls (49%). Children of MCM participants had significantly (p < .05) better physical outcomes: lower total dysmorphology scores, larger head circumferences, longer palpebral fissures, and higher midfacial measurements. Neurodevelopment results showed mixed outcomes. While Bayley developmental scores indicated that MCM offspring were performing significantly worse on most domains through 18 months, group scores equalized and were not significantly different on Kaufman Assessment Battery neurobehavioral measures by five years. Regression analyses indicated that offspring of women who received standard antenatal care were associated with significantly more negative outcomes than MCM offspring: a diagnosis of FAS (OR = 3.2; 95% CI: 1.093–9.081), microcephaly (OR = 5.3; 95% CI: 2.1–13.5), head circumference ≤10th centile (OR = 4.3; 95%CI: 1.8–10.4), and short palpebral fissures (OR = 2.5; 95% CI: 1.0–5.8). Conclusion At age five, proportionally fewer children of MCM participants qualified for a diagnosis of FAS, and proportionally more had physical outcomes indicating better prenatal brain development. Neurobehavioral indicators were not significantly different from controls by age five. KEY MESSAGES Multifaceted Case Management (MCM) was designed and employed for 18 months during the prenatal and immediate postpartum period to successfully meet multiple needs of women who had proven to be very high risk for birthing children with fetal alcohol spectrum disorders (FASD). Offspring of the women who participated in MCM were followed up through age five years and were found to have significantly better physical outcomes on multiple variables associated with fetal alcohol syndrome (FAS) and FASD, such as larger head circumferences and fewer minor anomalies, than those children born to equally at-risk women not receiving MCM. Fewer children of women receiving MCM were diagnosed with FASD than the offspring of equally-at-risk controls, and significantly (p = .01) fewer MCM offspring had FAS, the most severe FASD diagnosis.