Rising preterm birth rates¹ together with improved survival² identify a growing number of children surviving preterm birth. However, despite apparent progress in perinatal care, long-term morbidity rates have not decreased.³ Extremely or very preterm (EP/VP) birth (<32 weeks of gestation) is associated with higher risks for motor, learning, and behavior problems,^4-6 and particularly, cognitive impairment.⁷ Among the most immature infants (<28 weeks of gestation), impairment rates in 1 or more of these neurodevelopmental domains are reported to be as high as 70%.⁸ An important and frequently used measure of outcome is intelligence, as it provides a broad index of cognitive functioning and is substantially correlated with important life outcomes, such as physical and mental health,^9,10 academic achievement,¹¹ socioeconomic success,¹² and life chances.¹³ Earlier meta-analyses showed that preterm birth is associated with lower intelligence, with intelligence level being proportionally related to the degree of immaturity.^14,15 The compromised intelligence of children of EP/VP birth (EP/VP children) poses a significant burden on individuals, families, and society, and provides challenges for education and health care professionals.

Lower birth weight because of fetal growth restriction is associated with higher blood pressure later in life, but the extent to which preterm birth (<37 completed weeks' gestation) or very low birth weight (<1500 g) predicts higher blood pressure is less clear. We performed a systematic review of 27 observational studies that compared the resting or ambulatory systolic blood pressure or diagnosis of hypertension among children, adolescents, and adults born preterm or very low birth weight with those born at term. We performed a meta-analysis with the subset of 10 studies that reported the resting systolic blood pressure difference in millimeters of mercury with 95% CIs or SEs. We assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10 studies were composed of 1342 preterm or very low birth weight and 1738 term participants from 8 countries. The mean gestational age at birth of the preterm participants was 30.2 weeks (range: 28.8–34.1 weeks), birth weight was 1280 g (range: 1098–1958 g), and age at systolic blood pressure measurement was 17.8 years (range: 6.3–22.4 years). Former preterm or very low birth weight infants had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg [95% CI: 1.7–3.3 mm Hg]). For the 5 highest quality studies, the systolic blood pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6–5.0 mm Hg). We conclude that infants who are born preterm or very low birth weight have modestly higher systolic blood pressure later in life and may be at increased risk for developing hypertension and its sequelae.

The impact of nutrition on brain development in preterm infants has been increasingly appreciated. Early postnatal growth and nutrient intake have been demonstrated to influence brain growth and maturation with subsequent effects on neurodevelopment that persist into childhood and adolescence. Nutrition could also potentially protect against injury. Inflammation and perinatal infection play a crucial role in the pathogenesis of white matter injury, the most common pattern of brain injury in preterm infants. Therefore, nutritional components with immunomodulatory and/or anti-inflammatory effects may serve as neuroprotective agents. Moreover, growing evidence supports the existence of a microbiome-gut-brain axis. The microbiome is thought to interact with the brain through immunological, endocrine, and neural pathways. Consequently, nutritional components that may influence gut microbiota may also exert beneficial effects on the developing brain. Based on these properties, probiotics, prebiotic oligosaccharides, and certain amino acids are potential candidates for neuroprotection. In addition, the amino acid glutamine has been associated with a decrease in infectious morbidity in preterm infants. In conclusion, early postnatal nutrition is of major importance for brain growth and maturation. Additionally, certain nutritional components might play a neuroprotective role against white matter injury, through modulation of inflammation and infection, and may influence the microbiome-gut-brain axis.