MN O’Riordan^1,3, M Kiely¹, JR Higgins³, KD Cashman^1,2
1Departments of Food and Nutritional Sciences,
²Department of Medicine, and ³ANU Research Centre, Department of Obstetrics and Gynaecology, University College, Cork University
Maternity Hospital, Cork

Abstract
Low maternal vitamin D status has been associated with reduced intrauterine long bone growth and shorter gestation, decreased birth weight, as well as reduced childhood bone-mineral accrual. Despite data from other countries indicating low maternal vitamin D status is common during pregnancy, there is a dearth of information about vitamin D status during pregnancy in the Irish female population. Therefore, we prospectively assessed vitamin D nutritive status and the prevalence of suboptimal vitamin D status in a cohort of Irish pregnant women. The mean (SD) daily intake of vitamin D by the group of pregnant women was 3.6 (1.9) μg/day. None of the women achieved the recommended daily vitamin D intake value for Irish pregnant women (10 μg/day). Taking all three trimesters collectively, 14.3-23.7% and 34.3-52.6% of Irish women had vitamin D deficiency (serum 25 (OH) D <25 nmol/l) and insufficiency (serum 25 (OH) D 25-50 nmol/l), respectively during pregnancy. Both the levels of serum 25 (OH) D and the prevalence of vitamin D deficiency/adequacy were dramatically influenced by season, with status being lowest during the extended winter period and best during the extended summer period. These findings show that inadequate vitamin D status is common in Irish pregnant women.

Introduction
It has been reported that inadequate vitamin D status is common in healthy Irish females, particularly young girls and elderly women¹. Vitamin D deficiency has an established role in calcium metabolism and bone health², but there is growing evidence that it makes an important contribution to the development of a wide range of human pathologies (including inflammatory and autoimmune disease, cancer, hypertension, cardiovascular disease and diabetes mellitus^3,4). Vitamin D is also of critical importance for fetal development and for bone development in early-life^5,6. Moreover, low maternal vitamin D status has been associated with reduced intrauterine long bone growth and shorter gestation⁷, reduced childhood bone-mineral accrual8, and a low dietary intake of vitamin during pregnancy has been linked to decreased birth weight⁹. Low maternal vitamin D status may also have consequences for fetal “imprinting” that may affect neurodevelopment, immune function and chronic disease susceptibility later in life as well as soon after birth^6,10. However, there is a dearth of information about vitamin D status during pregnancy in the Irish female population. It is therefore of concern, that recent studies, in other countries, have shown that low maternal vitamin D status is common during pregnancy^11-13. The twofold aims of the present study were to prospectively assess the prevalence of suboptimal vitamin D status in a cohort of Irish pregnant women and to estimate habitual vitamin D intake in this population sub-group.

Methods
This study was a prospective observational study of vitamin D status in a cohort of pregnant Irish females [aged, 22-41 years (n 43)] during 2004-2006. The study group were recruited using convenience sampling in the Unified Maternity Services in Cork, Ireland (~52°N). All of the women were Caucasian and the parity ranged from 0-6 (all but one less than 3). None of the subjects were suffering from any condition likely to affect vitamin D status. Subjects were excluded if they were taking medicines (including supplements) or had any co-existing medical conditions likely to affect vitamin D status or calcium/bone metabolism. Each subject was invited to provide a fasting-morning blood sample. After an overnight fast, a blood sample (20 ml) was taken between 08.30 and 10.30 hours.

Vitamin D intake was assessed by use of a 128-item validated food frequency questionnaire¹⁴ (which has been developed specifically for Irish subjects) by a trained investigator. 25-hydroxyvitamin D (25 (OH) D) levels were measured in serum as described previously¹⁵. In the absence of agreed healthy ranges for serum 25 (OH) D during pregnancy, we used adult cut cutoff values to divide the women into: vitamin D deficient (<25 nmol/l), insufficient (25-50 nmol/l), and replete (>50 nmol/l)¹⁶. However, some experts are now advocating that values less than 80 nmol/l may reflect suboptimal vitamin D status6. The difference in mean 25 (OH) D) levels in women sampled during the dark and light season was assessed using an unpaired Student’s t-test.

Results
The mean, standard deviation and range of serum 25 (OH) D levels of the pregnant women as well as the percentages of women classified as vitamin D replete, insufficient and deficient during each trimester are shown in Table 1. Taking all three trimesters collectively, 14.3-23.7% and 34.3-52.6% of women had vitamin D deficiency (serum 25 (OH)D <25 nmol/l) and insufficiency (serum 25 (OH) D 25-50 nmol/l), respectively during pregnancy.

At the first visit (during trimester 1), the prevalence of vitamin D deficiency in women was 16.7% during the light season (April- September) and 30.4% during the dark season (Oct-March) (data not shown). The prevalence of vitamin D insufficiency in women was 41.7% during the light season and 60.9% during the dark season (data not shown). Mean serum 25 (OH) D levels for women sampled in the dark season were significantly (P<0.05) lower than that of women sampled in the light season (Mean (SD): 50.9 (23.4) v. 32.2 (12.2) nmol/l, respectively). None of the women had a serum 25 (OH) D concentrations >80 nmol/l (which is increasingly being considered by many as an optimal level6), even during the light season when vitamin D status would be expected to be highest¹⁷ (data not shown).

*Hill et al.16 [Serum 25 (OH) D: >50 nmol/l, replete;
25-50 nmol/l, insufficient; <25 nmol/l, deficient].

The mean (SD) daily intake of vitamin D by the group of pregnant women was 3.6 (1.9) µg/day. None of the women achieved the recommended daily vitamin D intake value for Irish pregnant women (10 µg/day)¹⁸. None of the women took a supplement containing vitamin D.

Discussion
Hollis and Wagner have recently expressed concern about the prevalence of low vitamin D status amongst pregnant women⁵ and have even suggested that vitamin D deficiency during pregnancy may be at epidemic levels6. In the present study, vitamin D insufficiency (defined as serum 25 (OH) D levels <50 nmol/l16) was prevalent (48.6-76.3%) in Irish women throughout pregnancy. In particular, the majority of women had vitamin D insufficiency during the extended winter period (Oct to March); with about 91% of women insufficient during trimester one. Even during the light season (April to September; during which one would expect vitamin D status to be much improved upon winter values1,15,17), about 41% of women still had insufficient vitamin D status. This is the first study, to our knowledge, to report vitamin D status data for Irish pregnant women. However, the findings are in line with those from other studies of pregnant women in countries elsewhere^7-11. Of even more of a concern are the extremely low percentages of Irish pregnant women (0-11.4%; across all three trimesters) who had adequate vitamin D status, if the more recently suggested definition of vitamin D adequacy was applied (serum 25(OH)D levels >80 nmol/l^5,6).

The reasons for the very high prevalence of low vitamin D status in these pregnant women are unclear. The relatively low wintertime serum 25 (OH) D levels among the women in the present study may be partially attributable to the relatively low habitual mean daily vitamin D intake (3.6 µg/day), relative to current recommendations (at least 10 µg/day)¹⁸. The intake level, however, is typical of that habitually consumed by the adult Irish non-pregnant female population (aged 18-50 years)¹⁹. On the other hand, and of concern in the present study, the high prevalence of serum 25 (OH) D levels below 50 nmol/l during the extended summer period might suggest not only a poor dietary intake, but low dermal synthesis of the vitamin from summer sunlight exposure.

When sunlight exposure is limited, dietary intake becomes much more important in relation to maintaining adequate vitamin D status. We have previously shown than vitamin D supplementation is a strong predictor of winter vitamin D status in Irish women16. None of the pregnant women in the present study were taking vitamin D-containing supplements, which might explain the low dietary intake values observed. This is not surprising as only 15% of Irish adults take a supplement containing vitamin D¹⁹. In the UK, 10 µg vitamin D/day is recommended throughout pregnancy, which the authorities acknowledge in practice means that vitamin D supplements should be advised²⁰. Clearly, supplement use is an important strategy by which many women could improve their vitamin D intake and reach the recommended intake value of 10µg/d¹⁸.

The low vitamin D status and poor dietary intake observed in this group of Irish pregnant women may have consequences not only for maternal skeletal health, but also for fetal development. Low maternal vitamin D status (serum 25 (OH)D levels less than 28 nmol/l) during the third trimester has been associated with reduced intrauterine long bone growth and shorter gestation⁷. In the present study, more than a quarter of women had serum 25 (OH)D levels less than 28 nmol/l during the third trimester. A low dietary intake of vitamin D during pregnancy has been linked to decreased birth weight, such that with each µg of vitamin D there could be an 11 g increase in birth weight⁹. Low maternal vitamin D status may also have implications for bone health during infancy and childhood. For example, low vitamin D status during pregnancy is a risk factor for vitamin D-dependent rickets in infants, a condition which appears to be re-emerging in many Western countries²¹. It has also been associated with reduced bone-mineral accrual in children at 9 years of age⁸.

The findings of the present study show that inadequate vitamin D status (serum 25 (OH) D levels below 50 nmol/l) is common in Irish pregnant women. This is of concern, in light of evidence that low maternal vitamin D status may also have consequences not only for skeletal health of the mother and child, but also the possibility that fetal “imprinting” arising from the low vitamin D status may affect neurodevelopment, immune function and chronic disease susceptibility later in life10. Therefore, there is a need to investigate methods of improving vitamin D status during pregnancy.

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