Purpose <p>Developmental defects of enamel (DDE) frequently occur in preterm infants (&lt; 37&#xa0;weeks) and in those with low birth weight (&lt; 2500&#xa0;g). Children with enamel hypoplasia and hypomineralisation are at an increased risk of developing caries lesions. Therefore, the present study aims to assess the influence of various perinatal risk factors on the prevalence and severity of DDE and dental caries in the primary teeth of high-risk infants.</p> Methods <p>The study, which included a sample of 240 high-risk children (aged 18–48 months), employed a cross-sectional analysis to assess the prevalence and severity of DDE in the primary teeth of high-risk infants admitted to the Neonatal Intensive Care Unit of a tertiary care centre. Oral examinations were done at follow-up.</p> Results <p>The mean chronological age was 29.48 ± 6.7 months; 112 (46.67%) children were preterm, and 105 (43.75%) had a birth weight of &lt;2500&#xa0;g. The prevalence of DDE and dental caries was 32.1% and 16.31%, respectively. DDE were significantly associated with extremely low birth weight (birth weight &lt; 1000) (<i>p</i> = 0.014; OR = 5.33). Dental caries was commonly associated with maternal pregnancy-induced hypertension (<i>p</i> = 0.032; OR = 2.4) and endotracheal intubation (<i>p</i> = 0.042; OR = 3.13). The prevalence of dental caries in maxillary incisors was higher in intubated when compared to non-intubated children (<i>p</i> = 0.024).</p> Conclusion <p>Dental caries and DDE are common in high-risk children. DDE might serve to be a valuable predictor for early risk assessment of dental caries. Consequently, early preventive measures and interventions could be implemented to prevent early childhood caries.</p>