Risk of mortality for small newborns in Brazil, 2011-2018: A national birth cohort study of 17.6 million records from routine register-based linked data.

Background: Preterm birth (<37 weeks), low birth weight (LBW,<2500g), and small for gestational age (SGA,<10th centile of birth weight for gestational age and sex) are markers of newborn vulnerability with a high risk of mortality. We estimated the prevalence of phenotypes combining these three markers and quantified the mortality risk associated with them.

Methods: Population-based cohort study using routine register-based linked data on all births and deaths in Brazil from January 1, 2011, to December 31, 2018. We estimated the prevalence of preterm, LBW, and SGA individually and for phenotypes combining these characteristics. The mortality risk associated with each phenotype: early neonatal, late neonatal, neonatal, post-neonatal, infant, 1-4 years, and under five years was quantified using mortality rates and hazard ratios (HRs) with 95% confidence interval (CI) were estimated using Cox proportional hazard models.

Findings: 17,646,115 live births were included. Prevalence of preterm birth, LBW and SGA were 9.4%, 9.6% and 9.2%, respectively. Neonatal mortality risk was 16-fold (HR=15.9; 95% CI:15.7-16.1) higher for preterm compared to term, 3 times higher (HR=3.4; (95% CI:3.3-3.4) for SGA compared to adequate for gestational age (AGA), and >25 times higher for LBW (HR=25.8; (95% CI:25.5-26.1) compared to normal birth weight (NBW). 18% of all live births were included in one of the small vulnerable newborn phenotypes. Of those 8.2% were term-SGA (4.7%NBW, 3.5%LBW), 0.6% were term-AGA-LBW, 8.3% preterm-AGA (3.8%NBW, 4.5%LBW) and 1.0% preterm-SGA-LBW. Compared to term-AGA-NBW, the highest mortality risk was for preterm-LBW phenotypes (HR=36.2(95%CI 35.6-36.8) preterm-AGA-LBW, HR=62.0(95%CI 60.8-63.2) preterm-SGA-LBW). The increased mortality risk associated with vulnerable newborn phenotypes was highest in the first month of life, with attenuated but continued high risk in the post-neonatal period and 1-4 years of age.

Interpretation: Our findings support the value of using more detailed phenotypes to identify those at highest risk. More granular data can inform care at the individual level, advance research, especially for prevention, and accelerate progress towards global targets such as the Sustainable Development Goals.

Funding: Wellcome Trust.