The effect of maternal and in-utero vitamin D status on pregnancy outcomes and children’s long-term health

Ph.D.Over the past decade, vitamin D deficiency has become a worldwide public health issue. Vitamin D deficiency in pregnant women has been suggested to link with several adverse pregnancy outcomes, such as pre-eclampsia, gestational diabetes mellitus (GDM), preterm birth and cesarean delivery. In-utero exposure to low vitamin D levels was also found to be associated with children’s risk of having atopy, asthma, wheeze and respiratory tract infection. Although Hong Kong is a subtropical region with adequate sunlight all year round, still over 90% of child-bearing age women and one third of infants were reported vitamin D deficient. There is still a paucity of research examining its associations with pregnancy outcomes and children’s long-term health in Chinese and in this locality.We aimed to investigate the maternal vitamin D status and its association with pregnancy outcomes and children’s long-term health in a cohort of mothers who had joined the Hyperglycemia and Pregnancy Outcome study between 2000 and 2006. Archived maternal and umbilical cord blood serum samples, which were collected at mid-gestation of pregnancy and at the time of delivery, respectively, were assayed for 25-hydroxyvitamin D [25(OH)-D] levels, by using ultra-performance liquid chromatography separation followed by serial tandem mass spectrometry.A total of 1501 maternal and 1320 umbilical cord serum samples were assayed. The median (IQR) of maternal and umbilical cord serum 25(OH)-D levels were 53.8 (41.6-68.1) and 39.7 (30.8-50.7) nmol/L respectively; 41.4% of the mothers met the diagnosis of vitamin D deficiency [i.e. 25(OH)-D levels <50 nmol/l]. Seasonal variations were observed in both maternal and umbilical cord vitamin D. There was moderate correlation between maternal and umbilical cord 25(OH)-D levels (r=0.30, P<0.01). There was no significant difference in the rates of GDM, gestational hypertension, pre-eclampsia, preterm birth and caesarean delivery between mothers with and those without vitamin D deficiency. However, umbilical cord 25(OH)-D level was found negatively associated with children’s fasting and 120 min glucose levels at the oral glucose tolerance tests, as well as pulse wave velocity at 7 years of age, independent of confounders (i.e. maternal age, GDM status, gestational weight gain, mode of delivery, children’s age and sex). The association of umbilical cord 25(OH)-D level with fasting plasma glucose was consistently observed in the offspring at 11 years of age. Furthermore, the rate of prehypertension/hypertension at 11 years of age among the children whose umbilical cord vitamin D level at the middle tertile was 3.10-fold of those at the upper tertile. Children whose umbilical vitamin D level were at the middle and lower tertile had 2.62- and 3.12-fold in the risk of abnormal glucose tolerance (i.e. impaired fasting glucose, impaired glucose tolerance or diabetes mellitus based on the definitions by American Diabetes Association) respectively of those whose umbilical vitamin D level were at the upper tertile. The results so far might suggest that in-utero exposure to low vitamin D level increase children’s future risk on hypertension and hyperglycaemia.在過去的十年中，維他命D缺乏已成為一個全球性的健康問題。 孕婦的維他命D缺乏顯示與嚴重的不良妊娠結局相關，如先兆子癇、妊娠期糖尿病、早產和剖宮產。 宮內接觸維他命D的水準過低也被發現與兒童過敏、哮喘、喘息和呼吸道感染的風險相關。 儘管香港位於亞熱帶地區，終年陽光充足，報告指出仍有90%育齡期婦女和1/3的嬰幼兒缺乏維他命D。 關於本地華人維他命D缺乏與妊娠結局和兒童長期健康情況的相關性仍缺乏文獻報導。我們通過隊列研究，其中母親曾于2000-2006年期間參與「高血糖與妊娠結局」研究，目的是探討母體維他命D與妊娠結局和兒童長期健康情況的相關性。 事先保存的母體血清標本和臍帶血清標本，分別採集于妊娠中期和分娩時，在此項研究中通過超高效液相色譜-串聯質譜方法，測定25羥基維他命 D水準。共有1501份母體血清標本和1320份臍帶血清標本經過測定。 母體和臍帶血清25羥基維他命的中位水準分別為53.8 (41.6-68.1) 和39.7 (30.8-50.7) nmol/L； 41.4% 孕婦被診斷為維他命D缺乏（即25羥基維他命 D <50 nmol/L). 母體和臍帶血清25羥基維他命D均表現出季節性的變化。 母體和臍帶血清的25羥基維他命D水準呈中度相關性（r=0.30, P