Poor Vitamin C Status Late in Pregnancy Is Associated with Increased Risk of Complications in Type 1 Diabetic Women: A Cross-Sectional Study

What is it about?

The importance of an adequate supply of micronutrients for normal pregnancy and fetal development is well established, particularly in the last trimester due to the increasing needs during the growth spurt of the fetus [1, 2]. As early as 1938, Teel and co-workers described the fetus as acting as a parasite on the mother’s vitamin C pool based on the observed gradient between maternal plasma and umbilical cord vitamin C (vitC) concentration at term, and the fact that the fetus apparently was preferentially supplied with vitC at the expense of the mother [3, 4, 5]. Subsequently, several studies have reported that pregnancy in healthy women is associated with a significant decrease in maternal vitC status during pregnancy [4, 6-8], perhaps partly due to increased blood volume in pregnancy. In experimental studies in guinea pigs, which like humans depend on an adequate supply of vitC through their diet, the offspring of vitC deficient guinea pigs have shown abnormalities of fetal bone development with atrophy of the osteoblasts and retarded osteoid formation [9]. Macroscopic fetal, uterine, and placental hemorrhages as well as poor attachment of the placenta to the uterus were also evident in vitC deficient animals [9]. Other experimental studies have shown an association of infertility, increased incidence of premature- and stillbirths and increased frequency of abortion with vitC deficiency [10, 11]. Intrauterine growth retardation was related to insufficient vitC status in guinea pigs [10]. More recently, experimental reports from animal studies demonstrated that CNS development in particular requires high amounts of vitC and may be impaired by an inadequate maternal supply [12-15]. In humans, abortion and premature rupture of the fetal membrane are related to low levels of vitC in plasma, leucocytes, and amniotic fluid [16-24]. Abnormalities of cardiotocography (CTG) and discolored/green amniotic fluid was also associated with low vitC status at the time of delivery [25]. Furthermore, vitC deficiency may play a leading role in placental abruption [26]. Human studies suggest that poor vitC status leads to fetal oxidative stress and impaired placental implantation due to oxidative stress is thought to increase risk of preeclampsia and miscarriages [27]. Epidemiological studies have also supported an association between vitC deficiency and preeclampsia [28,29]. However recently, human intervention studies using vitC in the prevention of preeclampsia have produced conflicting results [30,31,32]. Another study found no effect of vitamin C on prevention of spontaneous preterm birth [33]. A recent review concluded that a general recommendation of vitC supplementation to pregnant women was not warranted, but subpopulations such as women with vitC deficiency, smokers or diabetics were not discussed [34]. Thus in diabetic animals, experimental data support the amelioration of these risks by vitC supplementation [35,36,37,38]. In one human study, borderline gestational diabetes mellitus had an increased risk of adverse health outcomes compared with women no diabetes [39]. Another human controlled intervention study in type 1 diabetes mellitus (T1DM) pregnancy found a lower risk of premature birth in women receiving vitC and E supplementation and suggested regarding preeclampsia that vitC supplementation may be beneficial in women with a low antioxidant status at baseline; no effect on preeclampsia was observed in the T1DM cohort as a whole [40]. Another study also failed to prevent preeclampsia with vitC and E supplementation in women with T1DM and even a high risk pro-angiogenic haptoglobin genotype [41]. In T1DM, vitC levels are significantly lower than in non-diabetic subjects [42, 43]. This seems to be the case in the diabetic pregnancy, too, as we recently reported in a prospective study [8]. We found that the level of vitC was lower throughout pregnancy compared to the control group and hypovitaminosis C (vitC < 23 µmol/L [44]) was found in 51% of the diabetic women at some stage during pregnancy. Here, we report our evaluation of vitC status in the same cohort of pregnant T1DM women with regard to labor data and the outcome of pregnancies.

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