In our population of preterm infants, there was no association between tHcy measured at birth and IVH. We cannot exclude an association between tHcy level beyond birth and brain injury given that we measured values within the first 24 hours of life. Although an increased risk of other prothrombotic factors such as Factor V and prothrombin gene mutations in preterm infants with IVH was reported previously , IVH does not appear to be associated with an elevated tHcy in our study population as we had hypothesized.
We were able to successfully measure tHcy levels in 148 mostly preterm infants from filter paper specimens and describe the normal distribution of tHcy in our study population. The tHcy level in our infants is similar to the mean of 3.8 μmol/L described by Hongsprabhas et al in 9 Canadian preterm infants . Comparable values were also reported in a US study which described a mean tHcy level of 3.49 μmol/L from term umbilical arterial samples . Others have documented varying tHcy levels at birth from 3.8 to 7.9 μmol/L [13, 16, 27, 28]; some have suggested that these differences may be due to cultural variations or differences in fortification of foods . Higher tHcy values have been described in the umbilical vein as compared to umbilical artery and this may account for some of the variation as well .
Previous authors have suggested differences in Hcy based on gestational age with tHcy levels increasing with GA . We did not identify any correlation of tHcy with gestational age in our population of infants. There also were no differences between preterm and term tHcy level. Our findings of increased tHcy in infants exposed to maternal steroids and preeclampsia may have elevated the tHcy in the preterm population contributing to our lack of difference between term and preterm tHcy. To our knowledge, our investigation examined the widest variation in GA (22–36 weeks) and the lowest mean gestation (29 ± 4 weeks) in relation to tHcy. Our data are consistent with Minet who found no correlation between tHcy and gestational age . It has been previously described that elevated tHcy levels are associated with increased rates of prematurity while the natural history of maternal tHcy is to lower with pregnancy [7, 14]. In 434 Chinese women, the risk of preterm birth was nearly 4-fold higher among women with preconception tHcy concentrations ≥ 12.4 μmol/L compared with women who had lower concentrations . These opposing factors may also explain our lack of clear relationship between tHcy and GA.
We evaluated tHcy within the first day of life to negate any effects the neonatal diet may have. Based on our data we cannot comment on any association between tHcy levels in infants beyond the immediate postnatal period and IVH. The neonatal diet has been shown to clearly affect Hcy possibly through differences in intake of the essential vitamins necessary for folate metabolism [13, 18, 19]. Differences in maternal and neonatal Vitamin B12 levels account for much of the variation in tHcy. Preterm infants should not have received enteral nutrition or parenteral nutrient intake with folate or Vitamin B12 at the time of the blood draw. Therefore, the initial parenteral fluid should not have affected the tHcy value. Neonatal levels measured on the first day of life should predominantly be reflective of maternal levels and not influenced by diet or postnatal age changes.
We found lower tHcy in males as compared to females in our study sample. This has been described previously in newborn children by Refsum et al . The opposite has been reported in adult males with some finding slightly higher tHcy values . This finding in adults may be related to gender related differences in diet or hormonal influences which would be different in the postpubertal population compared to neonates. However, others have also reported no differences in tHcy related to gender; Minet found no difference in 123 term healthy infants as did Monsen et al in infants up to one year of age [19, 20].
Additionally, prenatal steroids were associated with higher tHcy values in our neonatal population. This is the first study to describe this effect. Analogous results of elevated tHcy levels have been documented in body builders using anabolic steroids . In our neonatal population, this difference in tHcy associated with prenatal steroids did not appear to be related to differences in neonatal morbidities and therefore may not be clinically important in at least the short term management of infants.
There were several limitations to our study. We only measured tHcy within 24 hours after birth. Future investigations to exclude an association between tHcy and IVH or cystic PVL might characterize tHcy beyond 24 hours but during the first several days of life, which is the highest risk period for IVH. The majority of IVH in preterm infants is known to occur in the first three days of life. Due to the small number of cases of cystic PVL in our study population, our population may have been under powered to show small differences in tHcy with cystic PVL. We also did not measure other likely important variables such as folate, vitamin B12, or maternal tHcy. However, given our limitations, our findings are similar to those recently presented by Kenet et al . Their group demonstrated no association in 166 preterm infants evaluated for multiple prothrombotic factors with neonatal complications. Importantly, most tHcy samples in their study group were measured in the first one to four weeks of life, but still demonstrated no association with IVH or PVL. Our current study differs largely in the timing of the measured tHcy; we obtained all tHcy samples within 24 hours, before the majority of IVH or cystic PVL occurs.