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dc.contributor.advisorTaylor, Barry
dc.contributor.advisorHoughton, Lisa
dc.contributor.authorWheeler, Benjamin John
dc.date.available2018-02-27T22:13:15Z
dc.date.copyright2018
dc.identifier.citationWheeler, B. J. (2018). Vitamin D during pregnancy, lactation, and childhood: Vitamin D deficiency rickets in New Zealand children and Vitamin D supplementation during exclusive lactation to improve both infant and maternal 25 hydroxyvitamin D status (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/7877en
dc.identifier.urihttp://hdl.handle.net/10523/7877
dc.description.abstractBackground Vitamin D is essential for calcium homeostasis and mineralisation of the skeleton. Vitamin D deficiency during pregnancy, infancy and childhood is common, and severe deficiency can lead to rickets. Rickets is a mineralisation defect at the epiphyseal growth plates specific to growing children. However, currently there are no national statistics on vitamin D deficiency rickets in New Zealand children, nor any data on longitudinal vitamin D status during pregnancy and lactation for the southern hemisphere. To prevent rickets and severe vitamin D deficiency, many countries use dietary fortification and recommend daily vitamin D supplementation to expectant mothers during pregnancy and infants during exclusive breastfeeding. This is not currently the case in New Zealand. Aims 1) To prospectively determine the annual incidence and characteristics of vitamin D deficiency rickets in New Zealand children 2) To determine the effect of two different intermittent monthly doses of maternal cholecalciferol on infant and maternal vitamin D status 3) To describe longitudinal vitamin D status during pregnancy and lactation in healthy women and their infants in Dunedin, New Zealand (latitude 45°S) Methods The New Zealand Paediatric Surveillance Unit (NZPSU) was utilised to prospectively collect cases of vitamin D deficiency rickets (defined by serum 25-hydroxyvitamin D <50nmol/L and elevated alkaline phosphatase levels, and/or radiological rickets) in New Zealand for 36 months between July 2010 and June 2013 inclusive. Concurrently, a three arm, randomised, double-blind, placebo-controlled trial recruited women from Dunedin (45°S) who were planning to exclusively breastfed. Women (n=90) were randomly assigned to receive either cholecalciferol (50,000 IU or 100,000 IU) or placebo monthly from week 4 to week 20 postpartum. The treatment effects relative to placebo were then estimated using a linear fixed-effects regression model. In addition, longitudinal data (3 antenatal and 2 postnatal time points) on vitamin D status during pregnancy and lactation (out to week 20 postpartum) was analysed (total n=126). Participants were the n=90 from the aforementioned trial, in combination with a further n=36 similarly recruited historical control mother-infant pairs. Data at the final postnatal time point week 20 was included only for those in the placebo and historical control groups. Results Fifty-eight children with confirmed vitamin D deficiency rickets were identified using the NZPSU. Median age was 1.4 years (range 0.3-11), and 95% were born in New Zealand; however the majority of mothers (68%) were not. The overall annual incidence of rickets in New Zealand children aged < 15 years was 2.2/100,000 (95%CI 1.4-3.5); with the incidence in those aged <3 years greater at 10.5/100,000 (95%CI 6.7-16.6). Key risk factors identified were: darker skin colour, Indian and African ethnicity, age <3 years, exclusive breastfeeding, southern latitude, and season (winter/spring). In the intervention trial, after 16 weeks of supplementation, maternal vitamin D status was significantly higher in both the 50,000 IU/month and 100,000 IU/month groups. For infants, the unadjusted mean changes in vitamin D status were not significantly different from the placebo group. However, after adjustment for season of birth, vitamin D-fortified formula intake, and skin colour the mean effect size for the 100,000IU/month group was 19.1nmol/L (95%CI 2.5-35.6; P=0.025). Analysis of the longitudinal pregnancy and lactation data for 126 maternal and infant pairs revealed high rates of both maternal and infant vitamin D deficiency during pregnancy and the first 20 weeks postnatal (71% still exclusively breastfeeding). Maternal vitamin D deficiency (25OHD < 50nmol/L) was seen at one or more time points (in those with data at all time points) during the full longitudinal study in 65% (52/80). Infant vitamin D deficiency was more common, seen in 76% at one or more time points. Deficiency at birth was found in 68% of infants, mean cord blood of 41nmol/L. At 20 weeks postpartum three infants with severe deficiency had developed secondary hyperparathyroidism (serum PTH values between 120 and 281pg/ml - Upper limit normal ≤65pg/ml). Season was the main variable affecting vitamin D status, with considerable variation in longitudinal status when examined by season of conception. In addition, stage of pregnancy also appears to exert an independent effect on vitamin D status once all other variables in the model were accounted for. Conclusions This thesis has demonstrated that in New Zealand, vitamin D deficiency during pregnancy, lactation and childhood remains an important health concern. In Dunedin, at 45°S, both infant and maternal deficiency during pregnancy and lactation is very common, and sometimes severe. Vitamin D deficiency rickets, the most severe manifestation of vitamin D deficiency is still occurring in New Zealand, with a higher incidence in children with mothers from India and Africa, and in children younger than three years who are currently or previously breastfed. While infancy and breastfeeding are risk factors for rickets, high-dose monthly maternal supplementation may also hold promise as an alternative dual maternal and infant supplementation strategy. Further research is now required to expand on the findings of the randomised controlled trial at the heart of this thesis.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectRickets
dc.subjectrickets
dc.subjectvitamin D
dc.subjectPregnancy
dc.subjectlactation
dc.subjectbreastfeeding
dc.subjectchildhood
dc.subjectbone
dc.titleVitamin D during pregnancy, lactation, and childhood: Vitamin D deficiency rickets in New Zealand children and Vitamin D supplementation during exclusive lactation to improve both infant and maternal 25 hydroxyvitamin D status
dc.typeThesis
dc.date.updated2018-02-27T21:44:47Z
dc.language.rfc3066en
thesis.degree.disciplineWomen's and Children's Health
thesis.degree.nameDoctor of Philosophy
thesis.degree.grantorUniversity of Otago
thesis.degree.levelDoctoral
otago.openaccessOpen
otago.evidence.presentYes
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