Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis

BackgroundGiven the high rates of vitamin D deficiency among pregnant women and possible effects on offspring health, a systematic review on this topic was conducted to help inform future practice guidelines.ObjectiveTo evaluate associations between maternal vitamin D supplementation, maternal 25-hydroxyvitamin D (25(OH)D) concentrations, and health outcomes.MethodsA PubMed literature search was conducted to identify studies that examined the health effects of vitamin D supplementation during pregnancy on maternal and infant health outcomes published from 2000 to 2016. Among 976 identified publications, 20 randomized clinical trials met the inclusion criteria. The initial search was extended to include five studies published between July 2016 and September 2018.Main outcome measuresMaternal and infant 25(OH)D concentrations, gestational diabetes, preeclampsia or gestational hypertension, cesarean section, maternal parathyroid hormone and calcium concentrations, and infant gestational age, birth weight, and birth length.Statistical analysesMean differences, odds ratios, and 95% CIs were calculated, only for the initial search, using separate random-effects meta-analyses for each outcome.ResultsEvidence was good or strong that maternal vitamin D supplementation significantly increased maternal (13 studies, n=18, mean difference, 14.1 ng/mL [35.2 nmol/L]; 95% CI=9.6-18.6 ng/mL [24.0-46.4 nmol/L]) and infant (nine studies, n=12; 9.7, 5.2, 14.2 ng/mL [24.2, 12.9, 35.5 nmol/L]) 25(OH)D concentrations, although heterogeneity was significant (I²=95.9% and I²=97.4, respectively, P<0.001). Evidence was fair that vitamin D supplementation significantly decreases maternal homeostatic model assessment-insulin resistance (five studies, n=7; −1.1, −1.5, −0.7) and increases infant birth weight (nine studies, n=11, 114.2, 63.4, 165.1 g), both had insignificant heterogeneity. A null effect of maternal supplementation on other maternal (preeclampsia, cesarean section) and infant (gestational age, birth length) outcomes was found.ConclusionsResults show vitamin D supplementation during pregnancy improves maternal and infant 25(OH)D concentrations and may play a role in maternal insulin resistance and fetal growth. To further inform practice and policies on the amount of vitamin D, which supports a healthy pregnancy, high quality dose-response randomized clinical trials, which assess pregnancy-specific 25(OH)D thresholds, and appropriately powered clinical outcomes are needed.     

Plasma 25-hydroxyvitamin D during pregnancy and small-for-gestational age in black and white infants

PurposeIn a prospective prenatal cohort study, we examined associations of second trimester and cord plasma 25-hydroxyvitamin D (25[OH]D) with small-for-gestational age (SGA) and the extent to which vitamin D might explain black/white differences in SGA.MethodsWe studied 1067 white and 236 black mother-infant pairs recruited from eight obstetrical offices early in pregnancy in Massachusetts. We analyzed 25(OH)D levels using an immunoassay and performed multivariable logistic models to estimate the odds of SGA by category of 25(OH)D level.ResultsMean (SD) second trimester 25(OH)D level was 60 nmol/L (SD, 21) and was lower for black (46 nmol/L [SD, 22]) than white (62 nmol/L [SD, 20]) women. Fifty-nine infants were SGA (4.5%), and more black than white infants were SGA (8.5% vs. 3.7%). The odds of SGA were higher with maternal 25(OH)D levels less than 25 versus 25 nmol/L or greater (adjusted odds ratio, 3.17; 95% confidence interval, 1.16–8.63). The increased odds of SGA among black versus white participants decreased from an odds ratio of 2.04(1.04, 4.04) to 1.68(0.82, 3.46) after adjusting for 25(OH)D.ConclusionsSecond trimester 25(OH)D levels less than 25 nmol/L were associated with higher odds of SGA. Our data raise the possibility that vitamin D status may contribute to racial disparities in SGA.     

Association Between Plasma 25-hydroxyvitamin D Concentrations and Incident Activities of Daily Living Disability: A Longitudinal Community-Based Cohort Study

ObjectivesA few studies of Western populations have found inconsistent results regarding the associations between vitamin D status and physical function. We explored the association between circulating vitamin D status [plasma 25-hydroxyvitamin D, 25(OH)D] and incident activities of daily living (ADL) disability among Chinese older adults.DesignCommunity-based longitudinal cohort study.Setting and ParticipantsA total of 2453 men and women (median age 84.0 years) in 7 Chinese longevity areas were included.MeasuresCox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident ADL, with adjustments for potential sociodemographic, and lifestyle confounders and biomarkers. Because there was a statistically significant interaction between plasma 25(OH)D and sex in relation to incident ADL, men and women were analyzed separately.ResultsThe median concentrations of plasma 25(OH)D were 46.6 nmol/L and 36.4 nmol/L for men and women, respectively. Compared with the lowest quartile in the fully adjusted model, the HR for incident ADL disability for the highest quartile was 0.55 (95% CI 0.36–0.85) for women; for men, a null association was indicated (HR_{highest vs lowest} 0.61, 95% CI 0.37–1.00). However, when using the recommended circulating 25(OH)D thresholds by the US Institute of Medicine, those with vitamin D sufficiency (≥50 nmol/L) had better ADL disability prognoses than those with vitamin D deficiency (<30 nmol/L) in both sexes (men HR 0.45, 95% CI 0.28–0.72; women HR 0.58, 95% CI 0.37–0.90).Conclusions and ImplicationsThe relationship between plasma 25(OH)D concentration and incident ADL disability was sex-specific among Chinese older adults. However, participants with recommended vitamin D sufficiency may have better disability prognoses in both sexes, suggesting that the recommended 25(OH)D concentration for bone health may extend to functional outcomes such as ADL disability in Chinese older adults.     

Residential Greenness Alters Serum 25(OH)D Concentrations: A Longitudinal Cohort of Chinese Older Adults

ObjectivesVitamin D deficiency is prevalent among older adults. We aimed to study whether residential greenness could alter serum 25(OH)D concentrations as a possible mechanism of residential greenness's positive health effects.DesignA longitudinal cohort study.Setting and ParticipantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with follow-up between 2012 and 2014.MethodsWe measured residential greenness by calculating annual average Normalized Difference Vegetation Index (NDVI) in a 500 m radius by using satellite images around each participant's residential address. Serum 25-hydroxyvitamin D (25(OH)D) concentration was dichotomized into 2 categories: nondeficiency (≥50 nmol/L) and deficiency (<50 nmol/L). We used the generalized estimating equation to examine the relationship between annual average NDVI and serum 25(OH)D.ResultsWe included 1336 participants in our analysis. The annual average NDVI was 0.49, and mean serum 25(OH)D was 43 nmol/L at baseline. Each 0.1-unit increase in annual average NDVI was associated with a 13% higher odds of vitamin D nondeficiency [95% confidence interval (CI): 1.01, 1.26]. The association was stronger among men [odds ratio (OR): 1.17, 95% CI: 1.02, 1.35] than women (OR: 1.08, 95% CI: 0.91, 1.29) and also stronger among those who were free of activities of daily living (ADL) disability at baseline (OR: 1.12, 95% CI: 1.00, 1.25). During the follow-up period, the participants who lived in greener areas were more likely to have an improved, rather than stable or deteriorated, vitamin D status (OR: 1.94, 95% CI: 1.51, 2.51).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are associated with higher serum 25(OH)D concentrations, which has implications for prevention of vitamin D deficiency among older adults.     

Serum 25(OH)D response to vitamin D3 supplementation: A meta-regression analysis

ObjectiveThe aim of this study was to review factors that influence serum 25(OH)D when patients are given vitamin D supplements.MethodsFrom a comprehensive search of all randomized controlled clinical trials with vitamin D₃ supplementation available on PubMed up to November 2011, we selected 33 with 43 treatment arms that included at least 30 adult participants. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses were performed for prespecified factors, including dose, duration, baseline serum 25(OH)D, and age.ResultsWith a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37 nmol/L (95% CI, 33–41) with significant heterogeneity among studies. Dose (slope: 0.006; P < 0.001), trial duration (slope: 0.21; P < 0.001), baseline serum 25(OH)D (slope: −0.19; P < 0.001), and age (slope: 0.42; P < 0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In subgroup analyses, the PMD was higher with doses ≥800 IU/d (39.3 nmol/L) after 6 to 12 mo (41.7 nmol/L), with baseline 25(OH)D <50 nmol/L (39.6 nmol/L), and in adults aged >80 y (40.5 nmol/L).ConclusionThis meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of ≥800 IU/d, after at least 6 to 12 mo, and even when baseline 25(OH)D is low and in adults >80 y.     

Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08–6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11–2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.     

Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth.     

Descriptive Epidemiology of Chronic Hypertension,Gestational Hypertension,and Preeclampsia in New York State, 1995–2004

We examined social, demographic, and behavioral predictors of specific forms of hypertensive disorders in pregnancy in New York State. Administrative data on 2.3 million births over the period 1995–2004 were available for New York State, USA, with linkage to birth certificate data for New York City (964,071 births). ICD-9 hospital discharge diagnosis codes were used to assign hypertensive disorders hierarchically as chronic hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia (eclampsia/severe or mild), or gestational hypertension. Sociodemographic and behavioral predictors of these outcomes were examined separately for upstate New York and New York City by calculating adjusted odds ratios. The most commonly diagnosed conditions were preeclampsia (2.57 % of upstate New York births, 3.68 % of New York City births) and gestational hypertension (2.46 % of upstate births, 1.42 % of New York City births). Chronic hypertension was much rarer. Relative to non-Hispanic Whites, Hispanics in New York City and Black women in all regions had markedly increased risks for all hypertensive disorders, whereas Asian women were at consistently decreased risk. Pregnancy-associated conditions decreased markedly with parity and modestly among smokers. A strong positive association was found between pre-pregnancy weight and risk of hypertensive disorders, with slightly weaker associations among Blacks and stronger associations among Asians. While patterns of chronic and pregnancy-induced hypertensive disorders differed, the predictors of gestational hypertension and both mild and severe preeclampsia were similar to one another. The increased risk for Black and some Hispanic women warrants clinical consideration, and the markedly increased risk with greater pre-pregnancy weight suggests an opportunity for primary prevention among all ethnic groups.     

Multinutrient-Fortified Juices Improve Vitamin D and Vitamin E Status in Children: A Randomized Controlled Trial

BackgroundProvision of fortified juices may provide a convenient method to maintain and increase blood fat-soluble vitamins.ObjectiveTo determine whether children consuming orange juice fortified with calcium and combinations of vitamins D, E, and A could increase serum 25-hydroxyvitamin D [25(OH)D], α-tocopherol, and retinol levels.DesignA 12-week randomized, double-blind, controlled trial.Participants/settingOne hundred eighty participants (aged 8.04±1.42 years) were recruited at Tufts (n=70) and Boston University (n=110) during 2005-2006. Of those recruited, 176 children were randomized into three groups: CaD (700 mg calcium+200 IU vitamin D), CaDEA (700 mg calcium+200 IU vitamin D+12 IU vitamin E+2,000 IU vitamin A as beta carotene), or Ca (700 mg calcium). Children consumed two 240-mL glasses of CaD, CaDEA, or Ca fortified orange juice daily for 12 weeks.Main outcome measuresSerum 25(OH)D, α-tocopherol, and retinol concentrations.Statistical analysesChanges in 25(OH)D, α-tocopherol, retinol, and parathyroid hormone concentrations were examined. Covariates included sex, age, race/ethnicity, body mass index, and baseline 25(OH)D, α-tocopherol, retinol, or parathyroid hormone levels. Multivariate models and repeated measures analysis of variance tested for group differences with pre–post measures (n=141).ResultsBaseline 25(OH)D was 68.4±27.7 nmol/L (27.4±11.10 ng/mL) ), with 21.7% of participants having inadequate 25(OH)D (<50 nmol/L [20.03 ng/mL]). The CaD group's 25(OH)D increase was greater than that of the Ca group (12.7 nmol/L [5.09 ng/mL], 95% CI 1.3 to 24.1; P=0.029). The CaDEA group's increase in α-tocopherol concentration was greater than that in the Ca or CaD groups (3.79 μmol/L [0.16 μg/mL], 95% CI 2.5 to 5.1 and 3.09 μmol/L [0.13 μg/mL], 95% CI −1.8 to 4.3), respectively (P<0.0001). Retinol levels did not change, and body weight remained as expected for growth.ConclusionsDaily consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E increased 25(OH)D and α-tocopherol concentrations in young children within 12 weeks.     

Gestational Weight Gain,Body Mass Index,and Risk of Hypertensive Disorders of Pregnancy in a Predominantly Puerto Rican Population

Objectives To prospectively evaluate the association between gestational weight gain (GWG), prepregnancy body mass index (BMI), and hypertensive disorders of pregnancy using the revised Institute of Medicine (IOM) Guidelines. Methods We examined these associations among 1359 participants in Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011 among women from the Caribbean Islands. Information on prepregnancy BMI, GWG, and incident diagnoses of hypertension in pregnancy were based on medical record abstraction. Results Four percent (n = 54) of women were diagnosed with hypertension in pregnancy, including 2.6 % (n = 36) with preeclampsia. As compared to women who gained within IOM GWG guidelines (22.8 %), those who gained above guidelines (52.5 %) had an odds ratio of 3.82 for hypertensive disorders (95 % CI 1.46–10.00; p_trend = 0.003) and an odds ratio of 2.94 for preeclampsia (95 % CI 1.00–8.71, p_trend = 0.03) after adjusting for important risk factors. Each one standard deviation (0.45 lbs/week) increase in rate of GWG was associated with a 1.74 odds of total hypertensive disorders (95 % CI 1.34–2.27) and 1.86 odds of preeclampsia (95 % CI 1.37–2.52). Conclusions for Practice Findings from this prospective study suggest that excessive GWG is associated with hypertension in pregnancy and could be a potentially modifiable risk factor in this high-risk ethnic group.     

Serum Vitamin D Concentrations,Time to Pregnancy,and Pregnancy Outcomes among Preconception Couples: A Cohort Study in Shanghai,China

Background: The role of vitamin D in reproductive health is still unclear. This study aimed to assess the effect of serum 25-hydroxyvitamin D (25(OH)D), among preconception couples, on fecundity, and the associations between 25(OH)D concentrations before and during pregnancy, and pregnancy outcomes. Methods: 200 preconception couples attempting to conceive were recruited and were followed-up until childbirth. Time to pregnancy was collected via telephone every two months or obtained via a questionnaire during pregnancy. Blood samples were collected to measure serum 25(OH)D levels from both partners at enrollment and from women during the second and third trimester of pregnancy. Results: Couples had higher conception rates within six months (adjusted odds ratio (aOR): 3.72, 95% CI: 1.16, 11.9) and reduced time to pregnancy (adjusted fecundability ratio (aFR): 1.50, 95% CI: 1.01, 2.23) if male partners had sufficient 25(OH)D compared with insufficient 25(OH)D. Compared to pregnant women with insufficient 25(OH)D in the third trimester of pregnancy, sufficient 25(OH)D was associated with reduced odds of anemia (OR: 0.22, 95% CI: 0.06, 0.82), longer gestational age (β: 0.53, 95% CI: 0.04, 1.01) and newborns’ higher ponderal index (β: 0.10, 95% CI: 0.01, 0.19). Conclusions: Sufficient serum 25(OH)D levels among preconception men or during pregnancy were associated with better reproductive health.     

More on the zinc connection.

Background: Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain.

Purpose: To report the distribution of values for serum 25-hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women, together with quantification of factors related to vitamin D status.

Setting: Nine largely agrarian counties in eastern Nebraska (～41° N).

Participants: A population-based sample of 1,179 women 55 years of age and older recruited into a four-year trial of calcium and vitamin D supplementation.

Methods: Baseline biochemical, dietary, and anthropometric measurements obtained on entry into trial.

Results: Serum 25(OH)D concentration at baseline varied cyclically with season, with the solar cycle explaining 2.9% of the total variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1 nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear relationship with serum parathyroid hormone (PTH), with the inflection point of the curve located at approximately 80 nmol/L. Supplements containing vitamin D were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless, approximately 4% of all women had values below the laboratory reference range and more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D concentration was positively correlated with the size of daily vitamin D supplement dose, and negatively with age, weight, and body mass index (P < 0.01 for all). In stepwise multiple linear regression models, weight, age, and supplement dose were independently correlated with seasonally adjusted serum 25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D concentration. Women taking supplements had only one-sixth the chance of having a 25(OH)D value below the reference limit of the assay, compared to women who did not use supplements.

Conclusions: Approximately two-thirds of this rural population fell below 80 nmol/L, a value considered to be the lower end of the optimal range. Based on the slope of 25(OH)D on supplement dose observed in these women, it would require an additional vitamin D input of nearly 2000 IU/d to reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to levels of 80 nmol/L or higher.     

Vitamin D Intake and Status in 12-Month-Old Infants at 63–66° N

The objective was to assess the vitamin D status in healthy 12-month-old infants in relation to quantity and sources of dietary vitamin D, breastfeeding and seasons. Subjects were 76 12-month-old infants. Serum levels of 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/L were considered indicative of vitamin D sufficiency and 25(OH)D < 27.5 nmol/L as being indicative of increased risk for rickets. Additionally, 25(OH)D > 125 nmol/L was considered possibly adversely high. Total vitamin D at 9–12 months (eight data collection days) included intake from diet and supplements. The mean ± SD of vitamin D intake was 8.8 ± 5.2 μg/day and serum 25(OH)D 98.1 ± 32.2 nmol/L (range 39.3–165.5). Ninety-two percent of infants were vitamin D sufficient and none at increased risk for rickets. The 26% infants using fortified products and supplements never/irregularly or in small amounts had lower 25(OH)D (76.8 ± 27.1 nmol/L) than the 22% using fortified products (100.0 ± 31.4 nmol/L), 18% using supplements (104.6 ± 37.0 nmol/L) and 33% using both (110.3 ± 26.6 nmol/L). Five of six infants with 25(OH)D < 50 nmol/L had no intake of supplements or fortified products from 0 to 12 months. Supplement use increased the odds of 25(OH)D > 125 nmol/L. Breastfeeding and season did not affect vitamin D status. The majority of infants were vitamin D sufficient. Our findings highlight the need for vitamin D supplements or fortified products all year round, regardless of breastfeeding.     

2009 IOM guidelines for gestational weight gain: how well do they predict outcomes across ethnic groups?

ABSTRACT

Objective: To determine whether the Institute Of Medicine's (IOM) 2009 guidelines for weight-gain during pregnancy are predictive of maternal and infant outcomes in ethnic minority populations.

Methods: We designed a population-based study using administrative data on 181,948 women who delivered live singleton births in Washington State between 2006–2008. We examined risks of gestational hypertension, preeclampsia/eclampsia, cesarean delivery, and extended hospital stay in White, Black, Native-American, East-Asian, Hispanic, South-Asian and Hawaiian/Pacific islander women according to whether they gained more or less weight during pregnancy than recommended by IOM guidelines. We also examined risks of neonatal outcomes including Apgar score <7 at 5 min, admission to NICU, requirement for ventilation, and a diagnosis of small or large for gestational age at birth.

Results: Gaining too much weight was associated with increased odds for gestational hypertension (adjusted OR (aOR) ranged between 1.53–2.22), preeclampsia/eclampsia (aOR 1.44–1.81), cesarean delivery (aOR 1.07–1.38) and extended hospital stay (aOR 1.06–1.28) in all ethnic groups. Gaining too little weight was associated with decreased odds for gestational hypertension and delivery by cesarean section in Whites, Blacks and Hispanics. Gaining less weight or more weight than recommended was associated with increased odds for small for gestational age and large for gestational age infants respectively, in all ethnic groups.

Conclusions: Adherence to the 2009 IOM guidelines for weight gain during pregnancy reduces risk for various adverse maternal outcomes in all ethnic groups studied. However, the guidelines were less predictive of infant outcomes with the exception of small and large for gestational age.

Abbreviations: GWG: Gestational weight gain; IOM/NRC; Institute of Medicine and National Research Council; NICU: Neonatal intensive care need for ventilation; SGA: Small for gestational age; LGA: Large for gestational age; BERD: Birth Events Records Database; CHARS: Comprehensive Hospital Discharge Abstract Reporting System; ICD: International Classification of Disease; LMP: Last menstrual period; OR: Odds ratio     

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka,Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.     

Risk factors differ between recurrent and incident preeclampsia: a hospital-based cohort study

PurposeTo examine whether risk factors, including prepregnancy body mass index (BMI), differ between recurrent and incident preeclampsia.MethodsData included electronic medical records of nulliparas (n = 26,613) delivering 2 times or more in Utah (2002–2010). Modified Poisson regression models were used to examine (1) adjusted relative risks (RR) of preeclampsia and 95% confidence intervals (CI) associated with prepregnancy BMI; (2) maternal risk factor differences between incident and recurrent preeclampsia among primiparous women.ResultsIn the first pregnancy, compared with normal weight women (BMI: 18.5–24.9), preeclampsia risks for overweight (BMI: 25–29.9), obese class I (BMI: 30–34.9), and obese class II/III (BMI: ≥35) women were 1.82 (95% CI = 1.60–2.06), 2.10 (95% CI = 1.76–2.50), and 2.84 (95% CI = 2.32–3.47), respectively, whereas second pregnancy–incident preeclampsia risks were 1.66 (95% CI = 1.27–2.16), 2.31 (95% CI = 1.67–3.20), and 4.29 (95% CI = 3.16–5.82), respectively. Recurrent preeclampsia risks associated with BMI were highest among obese class I women (RR = 1.60; 95% CI = 1.06–2.42) without increasing in a dose-response manner. Nonwhite women had higher recurrence risk than white women (RR = 1.70; 95% CI = 1.16–2.50), whereas second pregnancy–incident preeclampsia risk did not differ by race.ConclusionPrepregnancy BMI appeared to have stronger associations with risk of incident preeclampsia either in the first or second pregnancy, than with recurrence risk. Nonwhite women had higher recurrence risk.     

Prepregnancy obesity predicts poor vitamin D status in mothers and their neonates

Obesity is a risk factor for vitamin D deficiency, but this relation has not been studied among pregnant women, who must sustain their own vitamin D stores as well as those of their fetuses. Our objective was to assess the effect of prepregnancy BMI on maternal and newborn 25-hydroxyvitamin D [25(OH)D] concentrations. Serum 25(OH)D was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in their neonates' cord blood. We used multivariable logistic regression models to assess the independent association between BMI and the odds of vitamin D deficiency [25(OH)D <50 nmol/L] after adjustment for race/ethnicity, season, gestational age, multivitamin use, physical activity, and maternal age. Compared with lean women (BMI <25), pregravid obese women (BMI >or=30) had lower adjusted mean serum 25(OH)D concentrations at 4-22 wk (56.5 vs. 62.7 nmol/L; P < 0.05) and a higher prevalence vitamin D deficiency (61 vs. 36%; P < 0.01). Vitamin D status of neonates born to obese mothers was poorer than neonates of lean mothers (adjusted mean, 50.1 vs. 56.3 nmol/L; P < 0.05). There was a dose-response trend between prepregnancy BMI and vitamin D deficiency. An increase in BMI from 22 to 34 was associated with 2-fold (95% CI: 1.2, 3.6) and 2.1-fold (1.2, 3.8) increases in the odds of mid-pregnancy and neonatal vitamin D deficiency, respectively. The rise in maternal obesity highlights that maternal and newborn vitamin D deficiency will continue to be a serious public health problem until steps are taken to identify and treat low 25(OH)D.     

Perinatal Vitamin D and Calcium Status of Northern Canadian Mothers and Their Newborn Infants

Objective: This study was undertaken to examine the vitamin D and calcium status of mothers and their newborns.

Methods: The intakes of vitamin D and calcium were determined prenatally in 121 women including 33 Caucasians, 51 Inuits, and 37 Native Indians, living in the Inuvik zone of the Northwest Territories. Plasma concentrations of 25-(OH)-D and calcium were also measured in mothers as well as in their offspring at delivery.

Results: The daily mean vitamin D intake of native mothers, including Inuits and Indians, with (8.1±5.5 μg) and without supplements (3.4±2.5 μg) was significantly lower than that of non-native mothers (13.2±5.9 μg and 5.8±4.3 μg, respectively). According to the predicted prevalence of low vitamin D intake, there existed a higher risk of vitamin D deficiency without supplementation in both native (88.6% vs 48.4%) and non-native (63.5% vs. 15.1%) mothers. The trend for calcium intakes with and without supplementation was similar to vitamin D intake. At the point of delivery, the plasma levels of 25-(OH)-D were lower in native mothers (50.1±19.3 nmol/L) and their offspring (34.2±13.1 nmol/L) than their counterparts (59.8±29.4 nmol/L and 41.4±23.5 nmol/L, respectively). Its plasma levels in newborn infants averaged only 67% of their mothers. None of these infants showed clinical evidence of vitamin D deficiency. In fact, their plasma calcium levels were significantly higher than their mothers.

Conclusions: Plasma 25-(OH)-D concentrations of 60 to 70% of maternal levels may represent a “normal” range for newborn infants. However, a supplementation in native northern Canadian mothers during pregnancy and in their neonates during infancy may have a role to play in the prevention of vitamin D deficiency.     

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case–control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82–1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83–1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78–1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.     

Maternal Diet,C-Reactive Protein,and the Outcome of Pregnancy

Objective: To examine the association of high-sensitivity C-reactive protein (hsCRP), a systemic biomarker for the inflammatory process at entry to care, with pregnancy-induced hypertension/preeclampsia, adverse outcomes of pregnancy, and the maternal diet.

Design: Random sample (N = 520) with normal glucose tolerance from a large prospective cohort study of urban, low income, minority gravidae.

Results: During pregnancy, the highest tertile of hsCRP (range, 7.06–137.41 mg/L) was associated with significantly increased risks for early preterm delivery (<34 weeks). However, after stratification by maternal pregravid body mass index (BMI), risk for early preterm delivery <34 weeks (adjusted odds ratios [AOR] = 3.58, 95% confidence interval [CI] = 1.05–12.27), and pregnancy-induced hypertension (AOR = 2.66, 95% CI = 1.03–6.86) including preeclampsia (AOR = 2.72, 95% CI = 1.08–6.85) was shown to be specific to lean women (BMI <25) with high hsCRP. Increased hsCRP was unrelated to risk among overweight and obese gravidae. We found high hsCRP to be associated with diet. After stratification by BMI, dietary differences (higher intakes of protein and cholesterol with a lower intake of carbohydrate and a higher entry dietary glycemic index) were associated with increased hsCRP only among lean gravidae and not among those who were overweight or obese.

Conclusions: High hsCRP is a diet-related biomarker for serious complications and poor outcome in lean women with normal glucose tolerance.