BackgroundNewborns with one-or-more adverse birth outcomes (ABOs) are at greater risk of mortality or long-term morbidity with health impacts into adulthood. Hence, identifying ABO-associated factors is crucial for devising relevant interventions. For this study, ABOs were defined as prematurity (PTB) for gestational age <37 weeks, low birth weight (LBW) <2.5 kg, macrosomia >4 kg, asphyxia for a 5-minute Apgar score <7, congenital anomalies, and neonatal sepsis. This study aimed to assess factors associated with ABOs among babies delivered at the only hospital of Sao Tome & Principe (STP), a resource-constrained sub-Saharan-Central African country.MethodsA hospital-based unmatched case‒control study was conducted among newborns from randomly selected mothers. Newborns with one-or-more ABO were the cases (ABO group), while healthy newborns were the controls (no-ABO group). Data were collected by a face-to-face interview and abstracted from antenatal care (ANC) pregnancy cards and medical records. Multivariable logistic regression analysis was performed to identify ABO-associated factors considering a level of significance of α = 0.05.ResultsA total of 519 newborns (176 with ABO and 343 no-ABO) were enrolled. The mean gestational age and birthweight of cases and controls were 36 (SD = 3.7) weeks with 2659 (SD = 881.44) g and 39.6 (SD = 1.0) weeks with 3256 (SD = 345.83) g, respectively. In the multivariable analysis, twin pregnancy [aOR 4.92, 95% CI 2.25–10.74], prolonged rupture of membranes [aOR 3.43, 95% CI 1.69–6.95], and meconium- fluid [aOR 1.59, 95% CI 0.97–2.62] were significantly associated with ABOs. Eight or more ANC contacts were found to be protective [aOR 0.33, 95% CI 0.18–0.60, p<0.001].ConclusionModifiable factors were associated with ABOs in this study and should be considered in cost-effective interventions. The provision of high-quality ANC should be a priority. Twin pregnancies and intrapartum factors such as prolonged rupture of membranes and meconium-stained amniotic fluid are red flags for ABOs that should receive prompt intervention and follow-up.