A large majority of infants in this study (92.29%) achieved AF closure before the age of 24 months. Similar results were found in a study conducted by Liu et al. based on a cross-sectional survey of 104,147 children from 9 urban cities in China [10], who reported 94.2% with AF closure before 24 months. In another study by Kiesler et al. [3], the percentage was found to be approximately 96%. The differences may be explained by ethnic divergence. Unlike most of the previous relevant studies, our research extended the observation beyond 24 months, and showed that 99.87% of infants achieved AF closure before 36 months, which may help fill this gap in understanding AF development. The AFDC incidence rate of 7.71% in healthy infants is consistent with results from several other studies ranging from 4% to 7% [8,10,11], where the infants were reported to experience AF closure after 24 months, and some even beyond 36 months. As the AFDC infants in this study were considered healthy and within normal ranges for physical growth and development, it is concluded that this proportion of infants can be interpreted as normal variants within AF development and not related to any diseases.
The significantly larger AF size of AFDC infants found in our study indicated that AFDC in normal infants was related to congenital AF enlargement. Larger birth AF size, given normal brain development and skull osteogenesis, suggested longer time needed for full AF closure. Infants’ AF development is possibly correlated to weight and length/height development but not related to head circumference, which is in agreement with conclusions from Liu et al. [10], who also found no correlation between the time of AF closure and head circumference. However, Kumar et al. [12] and Oumer et al. [13] reported that AF size was only significantly related to newborn weight, and according to Wu Ting et al. [9] none of height, weight or head circumference has any relationship with AF size. As for the lack of a correlation between AF development and head circumference, it was probably due to the existence of the 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 are still able to expand to provide the space for brain development, which leads to a continually increasing head circumference regardless of when the AF closes[4,10].
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]. Additionally, Perera et al. also reported significant relationship between AF size and birth length [15], which is suggested to be related to maternal nutritional status during pregnancy. If the mother was able to provide sufficient nutrition in the late period of pregnancy, which means sufficient reserves of minerals and trace elements (e.g., calcium and phosphorus) for the developing fetus, the likelihood for AFDC will be lowered. As for the influence of gender, results in our study is in line with Oumer et al, who found that AF size of male infants was larger than that of their female counterparts [13]. Interestingly, we found both Vitamin A and D supplements, as well as the time of introducing complementary food were not associated with AFDC. The hypothesis for this is that our research was conducted in an economically developed city in China, where parents hardly had any financial problems providing their infants with enough vitamin supplements and balanced diets. Given the conclusion here that there was no significant difference between AFDC group and AFNC group in terms of nutrition and diets, it’s also highly suggested that a diagnosis of 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 since AFDC is not necessarily caused by nutritious factors.
Admittedly, there are some limitations to this study. Being a single-center study as it is, the study was likely not to be sufficiently representative and may have introduced certain selection bias. Besides, as this was also a retrospective study, it is limited in both sample size and data types; given this, it would be advisable that a case-control study of AFDC should be conducted in the future.