In this study, we analyzed UCB vitamin A levels, and its relationship with some medical morbidities in LPI. The median UCB vitamin A level of LPI was 0.754 (0.656, 0.892) μmol/L (table 1). Our median UCB vitamin A level was higher than a previous study where UCB vitamin A level of 0.55 ± 0.17 μmol/L was reported . However, that study did not mention the birth weight of LPI. In another study, UCB vitamin A level less than 1.05 μmol/L were measured in 22/56, and levels below 0.7 μmol/L only measured in 2/56 for gestational age < 33 weeks . These results were inconsistent. Two probable reasons were the different gestational age and birthweight of study participants. Nevertheless, preterm infants are prone to low vitamin A level . Our results showed the prevalence of low UCB vitamin A levels <0.7 μmol/L in LPI to be high (37.5%, 78/208). Several reasons could have accounted for this. For example, fetuses cannot synthesize vitamin A, and thus, primarily depend on maternal placental supply in late pregnancy . Also, retinol-binding protein (RBP) manufactured in the fetal liver during the final quarter of pregnancy plays a vital role in fetal vitamin A transportation. Premature infants are unable to synthesize enough RBP to transport vitamin A [27, 28]. This results in preterms being susceptible to having low vitamin A level.
We compared the effect of various factors on vitamin A levels, including gestational age, birth weight, 1 min Apgar score, 5 min Apgar score, delivery mode, and gender. LPI delivered via cesarean section is more likely to be low UCB vitamin A level < 0.7 μmol/L than those delivered via the vagina (table 2). Cesarean section was an independent factor for low UCB vitamin A level < 0.7 μmol/L. Vaginal deliveries without anesthesia are more stressful than cesarean deliveries, and this stress can increase maternal corticosteroids . Corticosteroids increase placental cord concentrations of vitamin A ; hence the lower and higher UCB vitamin A levels in cesarean section and vaginal deliveries, respectively. Contrastingly, Gonzalez- Corbella et al. reported no significant difference in vitamin A levels between vaginal and cesarean deliveries . We believe their inconsistent results had to do with the lower study participants (35 vaginal and 21 cesarean deliveries). Thus, based on our results, we are of the view that UCB vitamin A levels are significantly lower in cesarean section than vaginal delivery. Additionally, vitamin A levels in our study were not associated with birth weight, gestational age, and gender in LPI. These results were in line with previous studies [8, 30]. Retinol is signiﬁcantly higher in the sera of mothers giving preterm births as a result of preterm premature rupture of membranes . Thus, preterm premature rupture of membranes could affect vitamin A levels; nonetheless, the exact mechanisms is yet to be comprehensively elucidated.
Vitamin A acts on lung’s retinoic acid receptors to upregulate the transcription and expression of surfactant protein-B gene. This, in turn, promotes the synthesis of pulmonary surfactant . Besides, mild vitamin A deficiency has been shown to delay fetal lung maturation in animal studies. Surfactant proteins – A, B, and C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in vitamin A deficient fetuses . Kiatchoosakun et al. suggested that vitamin A supplementation can reduce intubation time and oxygen supplementation, while also shortening the length of hospital stay . However, another study reported no difference in the duration of oxygen therapy between vitamin A supplementation and control groups . In our study, we found vitamin A level < 0.7 μmol/L to not be an independent risk factor for hospitalization, oxygen supplementation, and RDS in LPI (table 3-5). Our result was consistent with a previously reported study . Therefore, vitamin A can promote lung surfactant synthesis, and thus, enhance lung maturation. However, this might not have a significant effect on LPI who have relatively matured lungs than other preterm infants. Having said that, further studies are warranted to clarify this.
Vitamin A can regulate specific and non-specific immunity, and protect against bacterial infection as an antioxidant . Plasma vitamin A concentrations are decreased during airway infection in premature neonates . In our study, however, UCB vitamin A level < 0.7 μmol/L was not an independent risk factor for sepsis (table 3).
We also found UCB vitamin A level < 0.7 was not an independent risk factor for hyperbilirubinemia in LPI (table 4). To the best our knowledge, there are limited studies reporting an association between vitamin A concentration and hyperbilirubinemia in LPI. As such, larger sample studies based on specific population are needed to corroborate this relationship. In addition, none of the neonates in this study suffered from BPD, NEC, and death. Thus, the relationship between UCB vitamin A levels and BPD, NEC or death in LPI requires further study.
Cesarean section, in this study, was an independent risk factor of not only hospitalization and oxygen supplementation, but also RDS (table 3-5). This result is supported by a recent meta-analysis. The authors reported that cesarean section was associated with an increased risk of neonatal RDS , with the underlying reason being the release of catecholamine . A high concentration of catecholamine in newborn infants promotes lung fluid absorption, and increases the release of surfactants . Hence, cesarean section increases the risk for RDS in LPI, which in turn, increases the risk of hospitalization and oxygen supplementation. Additionally, in comparison to gestational age ≥ 35 weeks, gestational age < 35 weeks increased the risk of hospitalization, hyperbilirubinemia and RDS. Thus, LPI of gestational age < 35 weeks are at more risk than those at gestational age ≥ 35 weeks. Similarly, compared to birthweight ≥ 2500 g, birth weight < 2500 g increases the risk of hospitalization and RDS. As such, these late preterm infants would need more attention.
It is worth noting that our present study has limitations. For example, the number of study participants was small. Besides, the study does not include the umbilical cord samples of term infants as control group of the study, although we did a subgroup analysis. Also, we did not measure other vitamins or micronutrients, which possibly might have an impact on the results.