According to the results of this three year follow-up regarding the AF development, we found that there 92.29% of included infants had AF closure before the age of 24 months. These data are similar to those of a study conducted by Liu et al. [10], who reported 94.2% of infants had AF closure before the age of 24 months, and which were based on a cross-sectional survey of 104,147 children from 9 urban cities in China. However, Kiesler et al. [3] found that approximately 96% of infants had AF closure before 24 months. The differences between these studies may be explained by ethnic divergence. The results of our study also showed that by the age of 36 months, 99.87% of infants had AF closure. Notably, most previous research stopped at the age of 24 months when observing AF development in children. Our data may help start filling this gap in developmental understanding. In addition, there were 61 infants among the 792 infants with AFDC, resulting in an AFDC incidence rate of 7.71% in healthy infants. This finding is consistent with a relevant study reporting the AFDC incidence range from 4-7% [8,10,11], which suggests that the time of AF closure in some infants is later than 24 months old, and with some not even having closure after 36 months. The proportion of this AFCD population is approximately 7.71%. As the infants in this study were healthy and within normal ranges for physical growth and development, we concluded that this occurrence could be interpreted as normal variation within AF development and not related to any diseases.
Moreover, we found that the median AF size of the AFDC group was larger than that of AFNC group, indicating that AFDC in normal infants was related to congenital AF enlargement. The larger the birth AF size is, and given normal brain development and skull osteogenesis, the longer time needed for total AF closure. Our results also showed that the median weight and length of AFDC group were lighter and shorter than those of AFNC group, and there was no significant difference in head circumference between the two groups. Collectively, these results suggest that AF development may be correlated to weight and length development rather than head circumference. These findings are also consistent with those of Liu et al. [10], who also found no correlation between the time of AF closure and head circumference. However, similar research conducted by Kumar et al. [12] and Oumer et al. [13] found that AF size was significantly related to only newborn weight. Comparatively, Wu Ting et al. [9] reported that the development of AF size was not related to height, weight or head circumference. As for why there was the lack of a correlation between AF development and head circumference, We speculate this was mainly due to the existence of bone seams in the infant skull, which are connected by elastic, membranous, fiber tissue. With the continuous ossification and maturation of the skull, the AF gradually closes, but the bone seams can still expand for providing the space for brain development, and the head circumference can still increase[4,10]. Therefore, it makes sense that the time of AF closure is not directly related to head circumference.
Finally, our results showed that heavier birth weight, longer birth length, larger congenital AF size, and being male were associated with AFDC. Previous studies by Roy et al.confirmed that AF size at birth was correlated to birth weight [14]. Perera et al. showed that AF size at birth was significantly related to birth length [15], and Oumer et al. reported that AF size in male infants was larger than that in female infants [13]. we speculated that this may have been related to maternal nutritional status during pregnancy. If the pregnant mother was able to provide sufficient nutrition for the developing fetus in the later period of pregnancy, which would mean that there were sufficient reserves of minerals and trace elements (e.g., calcium and phosphorus), and lowering the likelihood for AFDC. Interestingly, our results showed both Vitamin A/D supplements and the time of introducing complementary food were not associated with AFDC. We hypothesize this was due to the fact that our research was conducted in an economically developed city in China, with parents who had the financial capacity to provide their infants with enough vitamin supplements and a balanced diet. Given this, there was no significant difference between AFDC group and AFNC group. However, this result also indicated that a diagnosis AFDC should also be combined with an assessment of clinical symptoms and a biochemical examination, and large doses of vitamin D should not be blindly preferred in the treatment of AFDC.
There are some limitations to this study. First, it was conducted as a single-center study, which was likely not representative and may have introduced selection bias. As this study was also retrospective, sample size and data type were limited; given this, it would be advisable to conduct a case-control study of AFDC in the future.