A new study published in Pediatric Research has revealed that very preterm infants born at 22-31 weeks of gestation continue to exhibit significant deviations in growth patterns compared to the general population, even at age 6. The findings, based on longitudinal growth curves, indicate that these infants face persistent challenges in height, weight, and head circumference development, highlighting the need for ongoing monitoring and support.

Longitudinal Growth Patterns of Very Preterm Infants

The study, which tracked growth from term-equivalent age (40 weeks postmenstrual age) to 360 weeks (approximately 6 years), found that growth velocity in very preterm infants was consistently lower than the Japanese national growth standards up to 60 weeks postmenstrual age. After this point, growth trajectories began to align more closely with the reference norms, though the median height of these infants remained below the population median at 6 years of age.

Specifically, the growth velocity of head circumference, height, and weight was analyzed in three gestational age groups: 22-24 weeks, 25-27 weeks, and 28-31 weeks. Across all groups, the study found that infants born at a later gestational age had growth patterns more closely aligned with the reference population. However, even at 6 years of age, the median height of extremely preterm (EP) infants was still below that of the general population.

Height/length standard deviation scores (SDS) declined significantly between 40 and 60 weeks postmenstrual age, followed by a gradual recovery that did not reach the standard reference level. This trend is consistent with prior studies, including a longitudinal analysis of AGA infants born before 29 weeks of gestation, which also reported a decline in height and weight SDS between 40 and 60 weeks postmenstrual age.

Sex-Based Differences in Weight Gain

Notably, the study identified sex-based differences in weight gain. Female infants exhibited higher SDS values than males by 360 weeks postmenstrual age, despite weight SDS remaining below the reference median in all gestational age groups. This finding aligns with a large-scale U.S. cohort study of infants born at ≤28 weeks’ gestation and weighing <1250 g, which also reported higher post-discharge weight z-scores in girls than in boys.

Weight growth velocity was lower than the Japanese standard across all groups until approximately 70-80 weeks postmenstrual age, after which it converged with the reference values. The observed sex-based differences in weight gain velocity were also consistent with previously reported trends, indicating that female infants may have a slight advantage in weight recovery compared to their male counterparts.

At 40 weeks postmenstrual age, BMI-SDS values were above zero across all gestational age groups, followed by a rapid decline. From 60 weeks onward, BMI-SDS remained persistently below zero throughout the observational period (up to 360 weeks postmenstrual age) in EP infants, indicating that these children were consistently thinner than their age-matched peers in the general population.

Head Circumference and Neurodevelopmental Risk

Head circumference showed greater deviation from standard values with decreasing gestational age. No significant sex-based differences were identified in either SDS values or growth velocity for head circumference. Across all gestational age subgroups, SDS values declined until approximately 60 weeks postmenstrual age and then remained relatively stable throughout the remainder of the observation period.

Growth velocity was consistently lower than the reference standard from 40 to 60 weeks postmenstrual age but converged with the normative trajectory thereafter. Preterm infants with low birth weight are more likely to exhibit reduced head circumference compared with term-born peers, and head circumference growth has been shown to correlate with later neurodevelopmental outcomes.

In particular, head growth during NICU hospitalization is considered a critical predictor of subsequent neurological function. In this study, the degree of deviation in head circumference increased with decreasing gestational age, suggesting that infants born at earlier gestational ages may face a heightened risk of adverse neurodevelopmental outcomes.

Although previous large-scale studies have examined the association between gestational age and somatic growth, the number of extremely preterm infants, particularly those born before 28 weeks of gestation, has often been limited. A major strength of the present study lies in the subdivision of the VP cohort into three distinct gestational age groups (22-24, 25-27, and 28-31 weeks), each with a sufficient sample size for independent analysis.

The study’s findings demonstrate a clear positive association between gestational age and height/length growth, with trajectories approaching population standards as gestational age increased. Furthermore, by limiting the analysis to AGA infants, the researchers minimized the confounding effects of intrauterine growth restriction, thereby isolating the specific influence of gestational age on postnatal growth trajectories.

These results highlight the importance of long-term monitoring and support for extremely preterm infants, as growth deviations may persist into adulthood. The study also highlights the need for further research into the neurodevelopmental and health outcomes of these children, as well as the development of targeted interventions to address the challenges they face.