Study reveals critical factors behind neonatal mortality

By Dr. Liji Thomas, MDMay 11 2023Reviewed by Benedette Cuffari, M.Sc.

Over two million babies born alive died within the first four weeks of life in 2021, most of whom were low birth weight (LBW). A new research paper published in BJOG An International Journal of Obstetrics and Gynecology compares neonatal mortality rates among different types of neonates to identify those at the greatest risk of mortality.

Study: Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000–2020. Image Credit: Kristina Bessolova / Shutterstock.com

Introduction

In 2021, about 80% of neonatal deaths occurred among LBW babies with birth weights below 2,500 g. Over 66% of these babies were born before 37 weeks gestation.

Most LBW babies are either preterm or small for gestational age (SGA). When both factors are present, these babies are at a higher risk for illness and death in neonatal life, as well as childhood stunting, delayed development, and chronic conditions.

It is important from a public health perspective to understand which groups of babies contribute to the highest levels of mortality at a population level.”

Accordingly, researchers have proposed a set of newborn types based on gestational age, birth weight, and size for gestational age. The application of this classification might improve clinical care at the population level to ultimately promote the survival of all babies beyond the neonatal period.

In the current study, scientists used data from 15 national databases on live births and neonatal deaths collected for the Vulnerable Newborn Measurement Collaboration and the period extended between 2000 and 2020, covering over 125 million live births in countries from North America, Australia, Western Europe, the Middle East, Eastern Europe, and Asia.

Mortality and gestational age

Extremely preterm babies who were born before 28 weeks had a neonatal mortality rate of about 270 for every 1,000 live births for a median population attributable risk percent (PAR%) of 40. PAR% denotes the percentage of neonatal deaths attributable to a given risk factor. Thus, 40% of neonatal deaths were due to extreme prematurity.

Between 28-31 weeks gestation, the neonatal mortality rate declined to 32 for every 1,000 live births, with a PAR% of 11. Between 32-33 weeks gestation, this mortality rate further declined to 14, with a PAR% of 6. For late preterm births, which reflect infants born between 34 and 36 weeks gestation, the neonatal mortality rate was four for every 1,000, with a PAR% of 9.

Thus, babies born before 28 weeks were at 300 times higher risk of neonatal death as compared to those born at 37-42 weeks. The corresponding relative risk for 28-31, 32-34, and 34-36 weeks was significantly lower, from about 50 to six times higher as compared to the reference group.

Mortality and birthweight

Babies born weighing less than 1,000 g were 280 times more likely to die as newborns as compared to those of the reference birthweight of 2,500-4,000 g. With a birthweight between 1,000 and 1,500 g, the mortality risk was still 60 times higher than the reference group.

The mortality risk increased 20-fold among babies with birthweights = between 1,500 and 2,000 g and sixfold in babies above 2,000 g but less than the LBW cut-off of 2,500 g.

The median PAR% was 40 for those with birthweights below 1,000 g, about 12% between 1,000-1,500 g, as well as 7% and 6% for those with birthweights of 1,500-2000 g and 2,000-2,500 g, respectively.

The greatest rates of SGA births were in South Asia, many of which are low-income countries. Larger babies were also at a higher risk; however, this varied greatly between countries.

More research into neonatal types is required, as their application at the patient’s bedside could help distinguish disease risk in more specific and granular detail than the use of LBW alone.

Interactions between gestational age and birthweight

As compared to babies born weighing 2,500-4,000 g, babies born before 28 weeks and weighing less than one kilogram at birth were 280 times or more likely to die in the neonatal period, thus making them the most vulnerable subset of infants.

The median mortality rate was 32 for every 1,000 live births among preterm SGA babies, which increased their risk of death by 70 times. This amounted to about 21 and 17 for every 1,000 live births among preterm AGA and preterm LGA babies, respectively. This corresponded to 34- and about 30-fold higher risk, respectively.

Thus, all preterm non-SGA babies may be considered to be at comparable risk, which may simplify the classification.

Mortality rates dropped to less than five and 0. 5 in term SGA and term AGA/LGA babies, respectively. The PAR% was about 54 in this group as compared to 10 for preterm AGA babies. Preterm SGA and LGA babies contributed to about 10% and 8% of neonatal deaths, respectively, as compared to 4% for term SGA babies.

What are the implications?

Newborn premature babies are at the greatest risk of mortality, especially when they are also SGA. However, preterm AGA babies contribute the largest share of newborn deaths in the global population.

Given that LBW is a consequence of being born preterm and/or SGA age, dropping the LBW outcome may offer a more parsimonious and still useful approach to identifying newborns with common determinants.”

Mortality risk in the neonatal period is mainly due to prematurity. However, both gestational age and birthweight showed a dose-dependent relationship with neonatal mortality risk.

Given the major variation in risk by gestational age, we underline the value of considering this as a continuum, rather than a dichotomous cutoff at 37 weeks.”

The gross variation in mortality rates between regions points to the urgent need for further studies to identify the underlying reasons, which could be due to actual population risk differences or poor-quality healthcare. Biases due to flawed registration systems should also be considered as well.