Robert Fraser

The effect of pregnancy on bone density and bone turnover

During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total‐body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin‐like growth factor I (IGF‐I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P< 0.01) and legs (1.9%, P< 0.01) but decreased in the pelvis (−3.2%, P<0.05) and spine (−4.6%, P< 0.01) compared with prepregnancy values. All biochemical markers, with the exception of osteocalcin concentration, increased during pregnancy. The change in IGF‐I at 36 weeks was related to the change in biochemical markers (e.g., PINP, r = 0.72, P= 0.002). Pregnancy is a high‐bone‐turnover state. IGF‐I levels may be an important determinant of bone turnover during pregnancy. Elevated bone turnover may explain trabecular bone loss during pregnancy.

Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial

BACKGROUNDnMaternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation.nnnMETHODSnThe Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks gestation. Participants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks gestation (or as soon as possible before 17 weeks gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23.nnnFINDINGSnBetween Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related.nnnINTERPRETATIONnSupplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited.nnnFUNDINGnArthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

Validation of a food-frequency questionnaire for use in pregnancy.

OBJECTIVESnAs a part of an ongoing project to develop a nutritional screening tool, we evaluated the performance of a semi-quantitative food-frequency questionnaire (FFQ) in terms of validity in a Sheffield Caucasian pregnant population using two different statistical approaches--the correlation coefficient and the limits of agreement (LOA). The FFQ was designed specifically for pregnant women and previously used in a large-scale study.nnnDESIGNnA validation study.nnnSETTINGnA community-based field study of a general population of pregnant women booked for their first antenatal appointment at the Jessop Wing, Royal Hallamshire Hospital, Sheffield, UK.nnnSUBJECTSnOne hundred and twenty-three women of different socio-economic status, aged between 17 and 43 years, provided complete dietary data.nnnRESULTSnThe validity of the FFQ was tested against a series of two 24-hour recalls. As expected, the intakes of all examined nutrients, except for iodine, carotene, vitamin E, biotin, vitamin C and alcohol, were higher when determined by the FFQ than when determined by 24-hour recall. Pearsons correlation coefficient between the two methods ranged from 0.19 (added sugar, zinc) to 0.47 (Englyst fibre). The LOA were broader for some of the nutrients, e.g. protein, Southgate fibre and alcohol, and an increasing lack of agreement between the two methods was identified with higher dietary intakes.nnnCONCLUSIONSnThe FFQ gave useful estimates of the nutrient intakes of Caucasian pregnant women and appears to be a valid tool for categorising pregnant women according to dietary intake. The FFQ performed well for most nutrients and had acceptable agreement with the 24-hour recall.

Dietary assessment of a population of pregnant women in Sheffield, UK.

The present study examined the dietary intakes of a population of pregnant women living in the North of England. The objectives of the paper were to assess and describe the dietary intakes of the population and relate the findings to existing data on the diet of pregnant and non-pregnant women in the UK. A total of 250 pregnant women attending their first antenatal appointment at the Jessop Wing Hospital, Sheffield, UK were recruited. Information on their diet was assessed by an interviewer-administered semi-quantified food frequency questionnaire (FFQ). The mean intakes as assessed by the FFQ were similar to other studies of UK pregnant population; however Sheffield pregnant women had lower intakes of calcium and folate. Study findings were also related to the National Diet and Nutrition Survey and to the Estimated Nutrient Intakes (EAR). Of the study participants, 40 % did not meet the EAR for calcium, 67 % for iron and 69 % for folate. Subgroup comparisons suggested lower nutrient intakes of participants living in the 40 % most deprived electoral wards. The study findings suggest that the diet of pregnant women in Sheffield is characterised by low intakes of important nutrients for pregnancy such as folate and nutrient variations by electoral wards.

Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique

Objective To perform measurements of insulin resistance serially in pregnancy and after childbirth in normal women.

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group

MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR.BackgroundOsteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented.Methods/DesignWomen have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years.DiscussionAs far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.

Prenatal alcohol exposure and offspring cognition and school performance. A ‘Mendelian randomization’ natural experiment

Background There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and thus school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance. Methods We used mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) and performed both conventional observational analyses and Mendelian randomization using an ADH1B variant (rs1229984) associated with reduced alcohol consumption. Women of White European origin with genotype and self-reported prenatal alcohol consumption, whose offspring’s IQ score had been assessed in clinic (N = 4061 pairs) or Key Stage 2 (KS2) academic achievement score was available through linkage to the National Pupil Database (N = 6268), contributed to the analyses. Results Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher KS2 and IQ scores. In contrast, children whose mothers’ genotype predisposes to lower consumption or abstinence during early pregnancy had higher KS2 scores (mean difference +1.7, 95% confidence interval +0.4, +3.0) than children of mothers whose genotype predisposed to heavier drinking, after adjustment for population stratification. Conclusions Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual confounding by factors associated with social position and maternal education. The unconfounded Mendelian randomization estimates suggest a small but potentially important detrimental effect of small increases in prenatal alcohol exposure, at least on educational outcomes.

A controlled trial of a high dietary fibre intake in pregnancy — Effects on plasma glucose and insulin levels

SummaryNon-obese women in the second half of pregnancy were randomised into a control group receiving standard dietary advice and a group advised to make high fibre whole-food substitutions in their diets at every opportunity. Glucose and insulin profiles were performed over 24-h periods at 29 and 35 weeks gestation when the diets were equivalent in available carbohydrate, protein and fat, but the control group ingested 12.4 g dietary fibre/24 h and the high fibre group 51.4g/24h. Glucose homeostasis was similar in both groups but there was a significant attenuation of post-prandial insulin secretion in the high fibre group. It is suggested that the characteristic post-prandial peaks of plasma insulin observed in Western pregnant women are an unphysiological response to dietary fibre depletion.

A study exploring midwives' education in, knowledge of and attitudes to nutrition in pregnancy

OBJECTIVEnto explore midwives education in, knowledge of and attitudes to nutrition in pregnancy.nnnDESIGNnsurvey using questionnaire and interview schedule.nnnPARTICIPANTSna randomly selected sample of 77 Registered Midwives.nnnSETTINGnone English regional health authority.nnnMEASUREMENTS AND FINDINGSnqualitative and quantitative data collection methods. Midwife teachers were responsible for 95% of teaching in nutrition. 86% of midwives had received no education in nutrition following qualification. 46% of midwives achieved a poor score in nutrition knowledge. Considerable numbers of midwives felt unprepared to offer dietary advice to women from ethnic minority groups (36%), vegetarians (66%) and to women with pre-existing medical conditions (41%).nnnKEY CONCLUSIONnmidwives require more education in nutrition both during basic education and following qualification. IMPLICATIONS FOR EDUCATION PRACTICE: nutritional issues should be included in continuing education programmes available to qualified midwives.

Effect of Prenatal Alcohol Exposure on Childhood Academic Outcomes: Contrasting Maternal and Paternal Associations in the ALSPAC Study

Background The impact of low-to-moderate levels of alcohol consumption during pregnancy on child cognitive outcomes has been of recent concern. This study has tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is associated with lower school test scores at age 11 in the offspring via intrauterine mechanisms. Methods We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study based in the South West of England. Analyses were conducted on 7062 participants who had complete data on: maternal and paternal patterns of alcohol use in the first trimester and at 18 weeks gestation, childs academic outcomes measured at age 11, gender, maternal age, parity, marital status, ethnicity, household crowding, home ownership status and parental education. We contrasted the association of mothers alcohol consumption during pregnancy with childs National Curriculum Key Stage 2 (KS2) test scores with the association for fathers alcohol consumption (during the time the mother was pregnant) with childs National Curriculum Key Stage 2 (KS2) test scores. We used multivariate linear regression to estimate mean differences and 95% confidence intervals [CI] in KS2 scores across the exposure categories and computed f statistics to compare maternal and paternal associations. Findings and conclusions Drinking up to 1 unit of alcohol a day during pregnancy was not associated with lower test scores. However, frequent prenatal consumption of 4 units (equivalent to 32 grams of alcohol) on each single drinking occasion was associated with reduced educational attainment [Mean change in offspring KS2 score was −0.68 (−1.03, −0.33) for maternal alcohol categories compared to 0.27 (0.07, 0.46) for paternal alcohol categories]. Frequent consumption of 4 units of alcohol during pregnancy may adversely affect childhood academic outcomes via intrauterine mechanisms.