Vitamin D supplementation for cardiometabolic risk markers in pregnant women based on the gestational diabetes mellitus or obesity status : a randomized clinical trial.

PURPOSE: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity. DESIGN: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function). RESULTS: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM. CONCLUSIONS: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD. CLINICAL TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 ).

Timing of gestational diabetes diagnosis, gestational weight gains and offspring growth trajectory: a prospective birth cohort study.

BACKGROUND: The evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood. METHODS: A total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months. RESULTS: GDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04-1.36) and birth weight (OR 1.51, 95% CI 1.19-1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (ß 0.16, 95%CI 0.03-0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (P < 0.001). CONCLUSIONS: Exposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

BACKGROUND: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. OBJECTIVE: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. METHOD: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameter ≤10µm (PM10), sulfur dioxide (SO2), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. RESULTS: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of PM2.5, PM10, SO2 and CO were the 21th to 24th weeks of pregnancy. Every 10-µg/m3 increase in PM2.5 and PM10, 5-µg/m3 increase in SO2, and 0.1-mg/m3 increase in CO was associated with low maternal hemoglobin levels [-0.94g/L (95% confidence interval (CI): -1.15, -0.73), -1.31g/L (95% CI: -1.55, -1.07), -2.96g/L (95% CI: -3.32, -2.61), and -1.11g/L (95% CI: -1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. CONCLUSIONS: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Maternal 25(OH)D attenuates the relationship between ambient air pollution during pregnancy and fetal hyperinsulinism.

Inflammatory responses have been demonstrated to link air pollution with insulin resistance and type 2 diabetes in adults. However, few studies have focused on the relationship between prenatal air pollution and fetal ß-cell function and the mediating effect of systematic inflammation remains elusive. Whether the anti-inflammatory effect of vitamin D could attenuate the ß-cell dysfunction in early life warrants further investigations. We aimed to determine whether maternal blood 25(OH)D attenuates the associations of ambient air pollution during pregnancy with fetal hyperinsulinism mediated by maternal inflammatory response. A total of 8250 mother-newborn pairs were included between 2015 and 2021 in the Maternal & Infants Health in Hefei study. Weekly mean air pollution exposure to fine particles (PM2.5 and PM10), SO2, and CO was estimated across pregnancy. Maternal serum samples in the third trimester were used to measure the high-sensitivity c-reactive protein (hs-CRP) and 25(OH)D. Cord blood samples at delivery were collected for the measurement of C-peptide. Fetal hyperinsulinism was based on cord C-peptide >90th centile. An increased fetal hyperinsulinism risk was associated with per 10 µg/m3 increase in PM2.5 [odds ratios (OR): 1.45 (95% confidence interval (CI):1.32, 1.59)], per 10 µg/m3 increase in PM10 [OR = 1.49 (95% CI:1.37, 1.63)], per 5 µg/m3 increase in SO2 [OR = 1.91 (95% CI: 1.70, 2.15)], and per 0.1 mg/m3 increase in CO [OR = 1.48 (95% CI:1.37, 1.61)] across pregnancy. Mediation analysis showed a 16.3% contribution of maternal hsCRP to the relationship between air pollution throughout pregnancy and fetal hyperinsulinism. Air pollution-associated higher levels of hsCRP and risk of fetal hyperinsulinism could be attenuated by higher maternal 25(OH)D levels. Prenatal ambient air pollution exposures were associated with an increased fetal hyperinsulinism risk mediated by maternal serum hsCRP. Higher antenatal 25(OH)D levels could attenuate air pollution-induced inflammatory responses and hyperinsulinism risk.

Sleep patterns modify the association of 25(OH)D with poor cardiovascular health in pregnant women.

Background: The relationship between vitamin D status and gestational cardiovascular health (CVH) is inconsistent in previous studies. Emerging evidence shows that sleep behaviors are related to vitamin D metabolism. However, no studies evaluate the interaction of vitamin D and sleep behaviors on gestational CVH. Objective: We aimed to estimate the relationship between 25-hydroxyvitamin D [25(OH)D] concentrations and gestational CVH, and whether the relationship was modified by sleep behaviors. Methods: The data of this study was from a multicenter birth cohort study. A total of 9,209 pregnant women at 16-23 weeks of gestation were included. 25(OH)D concentrations were measured from collected blood. Sleep patterns consisted of major sleep behaviors including duration, chronotype, insomnia, snoring, and excessive daytime sleepiness. Data on poor CVH was based on four "clinical" CVH metrics, including body mass index, blood pressure, total cholesterol, and glucose levels. Results: The proportion of women with poor CVH was 25.0%. The relative risk (RR) (95%CI) of poor CVH was 0.67 (0.58-0.76) in women with 25(OH)D ≥ 50 nmol/L after multivariate adjustments. Lower 25(OH)D concentrations were significantly associated with poor CVH. Such association was also evident in subgroups analysis. We found a significant interaction of 25(OH)D (P for interaction = 0.01) with sleep patterns on the risk of poor CVH. A negative dose-response relation was observed between 25(OH)D concentrations and poor CVH risk in healthy or intermediate sleep, not poor sleep. 25(OH)D concentrations were lower and the risk of poor CVH was higher in pregnant women with poor sleep patterns (P < 0.05). Conclusion: Our study suggests that sleep patterns modify the association of 25(OH)D concentrations with the CVH among pregnant women.

Adequate 25(OH)D moderates the relationship between dietary inflammatory potential and cardiovascular health risk during the second trimester of pregnancy.

Background: Pro-inflammatory diets play an important role in developing cardiovascular disease (CVD). Vitamin D has been demonstrated to have an anti-inflammatory effect and promote cardiovascular health (CVH). However, it is unclear whether adequate vitamin D during pregnancy protects against poor CVH caused by pro-inflammatory diets. Objective: To investigate the association of pro-inflammatory diets with the cardiovascular risk (CVR) among pregnant women and whether such association was modified by vitamin D status. Methods: The study was based on a prospective birth cohort that included 3,713 pregnant women between 16 and 23 gestational weeks. In total, 25(OH)D concentrations and high-sensitivity C-reactive protein (hs-CRP) were measured from the collected blood. The dietary inflammatory potential was evaluated using the empirical dietary inflammatory pattern (EDIP) score based on a validated food frequency questionnaire. Gestational CVR was evaluated using the CVR score based on five "clinical" CVR metrics, including body mass index, blood pressure, total cholesterol, glucose levels, and smoking status. Results: The proportion of women with a CVR score >0 was 54.3%. We observed a positive association between the EDIP score and CVR score. Compared with the lowest quartile, the CVR score (ß = -0.114, 95% CI, -0.217, -0.011) and hs-CRP levels (ß = -0.280, 95% CI, -0.495, -0.065) were lower in the highest quartile (P for trend <0.05). Increased CVR connected with high EDIP score was observed only in women with 25(OH)D concentrations <50 nmol/L (RR = 1.85; 95% CI: 1.35, 2.54). Mediation analysis revealed that the proportion of association between the EDIP score and CVR score mediated by 25(OH)D was 28.7%, and the proportion of the association between 25(OH)D and the CVR score mediated by hs-CRP was 21.9%. Conclusion: The higher dietary inflammatory potential was associated with an increased CVR during pregnancy by promoting inflammation. Adequate vitamin D could exert anti-inflammatory effects and modify such association.

Associations of cord blood meta-inflammation and vitamin D with neurodevelopmental delay: A prospective birth cohort study in China.

Aim: To estimate the associations of cord meta-inflammatory markers with neurodevelopment, including the potential impact of cord blood vitamin D levels. Method: The prospective cohort study comprised 7198 participants based on the Maternal & Infants Health in Hefei study. Cord blood C-peptide, high-sensitive C-reactive protein (hsCRP), high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglycerides and 25(OH)D levels were measured. The Gesell Developmental Schedules were used to assess neurodevelopmental outcomes in offspring. Results: After adjusting potential confounders, per quartile increase in cord blood 25(OH)D concentrations was associated with a decreased risk of neurodevelopmental delay [hazard ratios (HR) 0.65 (95% CI 0.57, 0.74)]. Conversely, significant positive associations with cord blood serum C-peptide levels above the 90th percentile [HR 2.38 (95% CI 1.81, 3.13)] and higher levels of cord hsCRP (per quartile increase) [HR 1.18 (95% CI 1.01, 1.37)] with neurodevelopmental delay were observed. These associations could vary by quartiles of cord blood 25(OH)D levels: the adjusted HRs in neurodevelopmental delay comparing children with vs without hyperinsulinemia were 1.28 (95% CI: 1.03, 1.59) for quartiles 1 (lowest), and 1.06 (95% CI: 0.78, 1.44) for quartile 4 (highest). Conclusions: Immune activation and metabolic abnormalities in fetal circulation were associated with neurodevelopmental delay in offspring, which could be attenuated by higher cord blood 25(OH)D levels in a dose-response manner.

Mediterranean diet during pregnancy and infant neurodevelopment: A prospective birth cohort study.

Background: Embryonic neural development is associated with intrauterine nutritional status. However, few cohort studies estimated the relationship between maternal dietary patterns during pregnancy and offspring's early neurodevelopment. Objective: To examine the impact of the Mediterranean diet (MD) during pregnancy on infant neurodevelopment, including the potential mediating role of cord blood metabolites. Methods: Among 1,471 mother-child pairs in a prospective birth cohort study in Hefei, China, we investigated the associations between maternal MD score [calculated based on a validated food frequency questionnaire (FFQ)] and child neurodevelopment at infancy [assessed using Ages and Stages Questionnaires, Third Edition (ASQ-3)]. The cord blood metabolic markers (including C-peptide, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) were measured. Results: The MD score was negatively associated with communication domain developmental delays in infants [relative risk (RR) with 95% CI: 0.34 (0.16, 0.72)]. Compared with girls, boys born from mothers with lower MD scores during pregnancy were inclined to the failure of the communication domain [RRs with 95% CI for boys: 0.34 (0.14, 0.84); for girls: 0.26 (0.06, 1.18)]. Mediation analysis showed that the association between the maternal MD score and failure of communication domain mediated by C-peptide was 19.4% in boys but not in girls. Conclusion: Adhering to the MD during pregnancy was associated with a decreased risk of poor neurodevelopment, possibly mediated by lower levels of cord blood C-peptide.

Maternal Glycemia During Pregnancy and Early Offspring Development: A Prospective Birth Cohort Study.

CONTEXT: The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited. OBJECTIVE: To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association. METHODS: The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test at 24 to 28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 months in offspring were assessed by the Ages and Stages Questionnaires, Third Edition (ASQ-3). RESULTS: Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [relative risk (RR) with 95% CI: 1.97 (1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG) and 2-h plasma glucose (2-h PG) with 1 SD change were at higher risks in failing the personal social domain of ASQ-3 [RRs with 95% CI for FPG: 1.49 (1.09, 2.04); for 1-h PG: 1.70 (1.27, 2.29); for 2-h PG: 1.36 (1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide. CONCLUSIONS: Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 months.

The role of neonatal vitamin D in the association of prenatal depression with toddlers ADHD symptoms: A birth cohort study.

BACKGROUND: Vitamin D has been demonstrated a "neuroprotective" effect, but it is unclear whether early-life adequate vitamin D protect adverse neurodevelopment. We aimed to examine the role of neonatal vitamin D in the association of maternal depression (MD) symptoms with toddlers ADHD. METHODS: Participants included 1 125 mother-infant pairs from the China-Anhui Birth Cohort study. MD was assessed by the Center for Epidemiological Studies Depression Scale (CES-D) at 30-34 gestational weeks. Toddlers ADHD was reported by the Conners' Hyperactivity Index (CHI) at 48-54 months postpartum. Multiple logistic regression models were performed to evaluate the association of maternal depressive score and toddlers ADHD while cord blood 25(OH)D levels were stratified. RESULTS: Toddlers of mothers with higher depression score were at higher risk of ADHD (20.1% vs 11.1%, P = 0.003; adjusted RR=1.75, 95% CI: 1.10-2.81). Among toddlers with neonatal vitamin D deficiency (VDD), ADHD risk was significantly increased with maternal MD (adjusted RR=3.74, 95% CI: 1.49-9.41), but the association was not found in toddlers with neonatal vitamin D adequacy (VDA). Compared to toddlers without MD, toddlers with both MD and neonatal VDD had higher risk of ADHD (adjusted RR=3.10, 95% CI: 1.44-6.63). But the risk did not significantly increase in toddlers with MD and neonatal VDA (adjusted RR=1.53, 95% CI: 0.86-2.72). LIMITATIONS: Maternal depressive symptoms in early pregnancy and anxious symptoms were needed to include. CONCLUSION: This prospective study indicated that the detrimental effect of maternal prenatal depressive symptoms on offspring's ADHD symptoms strengthened in toddlers with neonatal VDD.

Vitamin D status affects the relationship between lipid profile and high-sensitivity C-reactive protein.

BACKGROUND: The biological pathways through which vitamin D is involved in the regulation of systemic inflammation remain largely unknown. OBJECTIVE: The objective of this study was to evaluate the role of vitamin D status on the relationship between lipid profile and high-sensitivity C-reactive protein (hs-CRP) in pregnant women. DESIGN: Serum 25-hydroxyvitamin D (25(OH)D), hs-CRP, and indicators of lipid profiles (total cholesterol, TC; triglyceride, TG; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C), were measured in 2479 pregnant women during the second trimester. Potential confounding including maternal sociodemographic characteristics, perinatal health status, diet, and lifestyle was prospectively collected. Multiple regression models and cubic models were used to evaluate the associations. RESULTS: There was a significant non-linear relationship between lipid profile (TC, TG, HDL-C, LDL-C) and hs-CRP (P < 0.05). Increased serum 25(OH)D was significantly associated with decreasing TC, TG, HDL-C, LDL-C, and hs-CRP levels. Compared with medium levels of lipids group, pregnant women with higher levels of TC or TG have higher levels of hs-CRP, and pregnant women with lower levels of TC, HDL-C or LDL-C also have higher levels of hs-CRP in the vitamin D deficient group, and there was a significant correlation between low levels of TG and decreased hs-CRP (adjusted ß for TG: -0.063, 95%CI: - 0.120,-0.007) in the non-vitamin D deficient group. Mediators that had appreciable shares of the associations between 25(OH)D and hs-CRP was TG (10.2% of the association; ß = - 0.011; total indirect effect: 95% CI: - 0.019, - 0.002). The cubic model suggested that a steep increase in the adjusted regression coefficient of lipid with hs-CRP up to 50 nmol/L of 25(OH)D, and the highest adjusted regression coefficients were observed in pregnant women with 25(OH)D above 50 nmol/L. CONCLUSION: Our findings suggest that high levels of vitamin D during pregnancy may improve lipid profile levels and inhibit elevated hs-CRP induced by high lipid metabolism.

The role of parathyroid hormone during pregnancy on the relationship between maternal vitamin D deficiency and fetal growth restriction: a prospective birth cohort study.

Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted ß = -49·4 g, 95 % CI -91·1, -7·8, P < 0·05; for severe VDD: adjusted ß = -79·8 g, 95 % CI -127·2, -32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted ß = -44·5 g, 95 % CI -82·6, -6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted ß = -124·7 g, 95 % CI -194·6, -54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.

The association of vitamin D status and supplementation during pregnancy with gestational diabetes mellitus: a Chinese prospective birth cohort study.

BACKGROUND: Previous studies have shown conflicting findings regarding the relation of vitamin D status and supplementation during pregnancy with gestational diabetes mellitus (GDM). Most of these studies hypothesized that 25-hydroxyvitamin D [25(OH)D] concentrations were associated with GDM risk and glucose metabolism based on linear association models. OBJECTIVES: We aimed to estimate the associations of 25(OH)D concentrations and vitamin D supplementation with GDM risk and glucose metabolism and determine the threshold concentrations of 25(OH)D that could significantly affect glucose metabolism and GDM risk. METHODS: In a prospective birth cohort study, we collected information about sociodemographic characteristics, health status, and lifestyle from 4984 pregnant women. Vitamin D supplementation and 25(OH)D concentrations were assessed in the second trimester. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. RESULTS: A total of 922 (18.5%) women were diagnosed with GDM. Compared with women with 25(OH)D concentrations <25 nmol/L, the GDM risk was significantly lower in women with 25(OH)D concentrations ranging from 50 to 75 nmol/L (RR: 0.74; 95% CI: 0.58, 0.95) and >75 nmol/L (RR: 0.40; 95% CI: 0.22, 0.70). The curve-fitting models suggested a significant large reduction in GDM risk, fasting plasma glucose, and area under the curve of glucose with increasing 25(OH)D concentrations only for concentrations >50 nmol/L. Consistently, GDM risk was significantly reduced only in women who took 400-600 IU vitamin D/d (RR: 0.83; 95% CI: 0.70, 0.97) with a mean 25(OH)D concentration of 50 nmol/L but not in women taking vitamin D sometimes with a mean 25(OH)D concentration of 40 nmol/L. CONCLUSIONS: GDM risk was significantly reduced only in pregnant women with 25(OH)D concentrations >50 nmol/L. Pregnant women taking 400-600 IU vitamin D/d with mean 25(OH)D concentrations of 50 nmol/L had a lower risk of GDM.

Current Recommended Vitamin D Prenatal Supplementation and Fetal Growth: Results From the China-Anhui Birth Cohort Study.

Context: Maternal vitamin D insufficiency has been associated with fetal growth restriction. However, the effect of maternal vitamin D supplementation on fetal growth has not been confirmed. Objective: To assess the effect of maternal vitamin D supplementation recommended by the Institute of Medicine (IOM) during pregnancy on the neonatal vitamin D status and the risk of small for gestational age (SGA). Design and Participants: As part of the China-Anhui Birth Cohort study, maternal sociodemographic characteristics, food intake, lifestyle, information on vitamin D supplementation, and birth outcomes were prospectively collected. For participants, 600 IU/d of vitamin D3 was routinely advised to take during pregnancy. Cord blood levels of 25-hydroxyvitamin D [25(OH)D], calcium, and phosphorus were measured in 1491 neonates who were divided into three groups based on the duration of maternal vitamin D supplementation during pregnancy. Results: Mean cord blood concentrations of 25(OH)D were 3.5 nmol/L higher [95% confidence interval (CI), 0.8, 6.2] in neonates (median, 37.9 nmol/L) whose mother took vitamin D supplementation for >2 months during pregnancy compared with those (median, 34.3 nmol/L) whose mother did not take any supplement. These significant differences on cord blood concentrations of 25(OH)D occurred regardless of the season of birth. The adjusted risk of SGA in pregnant women with vitamin D supplementation for >2 months was significantly decreased than that in women without any vitamin D supplementation (11.8% vs 6.9%; adjusted odds ratio = 0.53; 95% CI, 0.32, 0.87). Conclusions: The findings from China suggest that maternal vitamin D supplementation recommended by the IOM results in a slight but significantly higher fetal level of 25(OH)D and improves fetal growth.

Maternal depression attenuates newborn vitamin D concentrations in winter-spring: a prospective population-based study.

We aimed to investigate whether the newborns of mothers with maternal depression (MD) had lower vitamin D levels than newborns of non-MD (NMD) mothers and identify the potential mechanism underlying this association. Maternal depressive symptoms in late pregnancy and concentrations of cord blood 25 hydroxyvitamin D (25(OH)D) were measured in 1491 mother-infant pairs. Data on maternal sociodemographic characteristics, health status, lifestyle and birth outcomes were prospectively collected. For infants born in winter-spring, the infants of MD mothers had significantly reduced concentrations of 25(OH) D (adjusted ß = -3.51 nmol/L; 95% CI: -6.19, -0.84; P = 0.010) and lower birth weight (3267 ± 470 g vs 3348 ± 598 g, F = 4.64, P = 0.031), compared with the infants of NMD mothers. A significant, inverse linear relationship was noted between maternal depression scores and the concentration of 25(OH)D for infants born in winter-spring (adjusted ß = -0.158; 95% CI: -0.259, -0.057). The significant, inverse linear relationship between maternal depression scores and fetomaternal ratios of 25(OH) D was also observed among the infants born in winter-spring (adjusted ß = -0.005; 95% CI: -0.008, -0.003). MD appears to significantly attenuate the vitamin D concentrations and birth weight of infants born in winter-spring. A decreased fetomaternal ratio of 25(OH)D might be involved in this biological pathway.

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 ß = -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.

Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.

Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers.

BACKGROUND: Little is known about the relation between vitamin D status in early life and neurodevelopment outcomes. OBJECTIVE: This study was designed to examine the association of cord blood 25-hydroxyvitamin D [25(OH)D] at birth with neurocognitive development in toddlers. METHODS: As part of the China-Anhui Birth Cohort Study, 363 mother-infant pairs with complete data were selected. Concentrations of 25(OH)D in cord blood were measured by radioimmunoassay. Mental development index (MDI) and psychomotor development index (PDI) in toddlers were assessed at age 16-18 mo by using the Bayley Scales of Infant Development. The data on maternal sociodemographic characteristics and other confounding factors were also prospectively collected. RESULTS: Toddlers in the lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI: -12.4, -2.82; P = 0.002) and 8.04 (95% CI: -12.9, -3.11; P = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Unexpectedly, toddlers in the highest quintile of cord blood 25(OH)D also had a significant deficit of 12.3 (95% CI: -17.9, -6.67; P < 0.001) points in PDI scores compared with the reference category. CONCLUSIONS: This prospective study suggested that there was an inverted-U-shaped relation between neonatal vitamin D status and neurocognitive development in toddlers. Additional studies on the optimal 25(OH)D concentrations in early life are needed.

Sex-specific and time-dependent effects of prenatal stress on the early behavioral symptoms of ADHD: a longitudinal study in China.

There is increasing evidence that prenatal stressful life events (SLEs) may be a potential risk factor for attention-deficit hyperactivity disorder (ADHD), but the sex-specific and time-dependent effects of prenatal stress on ADHD are less clear. In this prospective longitudinal study, data on prenatal SLEs during different stages of gestation and indicators of buffers against stress, including maternal social support and avoidance coping, were obtained from 1765 pregnant women at 32 weeks of gestation. The behavioral symptoms of ADHD in children aged 48-54 months were evaluated by reports from the parents. There were 226 children (12.8%) above the clinically significant cutoff for ADHD. After adjusting for potential confounders, boys whose mother experienced severe SLEs in the second trimester had a significantly increased risk (OR = 2.41, 95% CI: 1.03-5.66) of developing ADHD symptoms compared with boys whose mothers did not experience severe SLEs at this time. However, no significantly increased risk of ADHD symptoms was observed in girls born to mothers experienced prenatal severe SLEs. Additionally, significant interaction effects of prenatal SLEs, social support and coping style on ADHD symptoms were found in males. Boys whose mothers experienced severe SLEs during the second trimester accompanied by a higher score for avoidance coping (OR = 3.31, 95% CI: 1.13-9.70) or a lower score for social support (OR = 4.39, 95% CI: 1.05-18.31) were likely to be at a higher risk for ADHD symptoms. The epidemiological evidence in this prospective follow-up study suggests that the effect of prenatal SLEs on ADHD symptoms in offspring may depend on the timing of prenatal stress and may vary according to the sex of the offspring.

Does prenatal maternal stress impair cognitive development and alter temperament characteristics in toddlers with healthy birth outcomes?

AIM: The aim of this study was to assess the cognitive and behavioural development of children with healthy birth outcomes whose mothers were exposed to prenatal stress but did not experience pregnancy complications. METHOD: In this prospective study, self-reported data, including the Prenatal Life Events Checklist about stressful life events (SLEs) during different stages of pregnancy, were collected at 32 to 34 weeks' gestation. Thirty-eight healthy females (mean age 27 y 8 mo, SD 2 y 4 mo) who were exposed to severe SLEs in the first trimester were defined as the exposed infant group, and 114 matched comparison participants were defined as the unexposed infant group (1:3). Maternal postnatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. The Bayley Scales of Infant Development and the Toddler Temperament Scale were used to evaluate the cognitive development and temperament characteristics of the infants with healthy birth outcomes when they were 16 to 18 months old. RESULTS: A randomized block multivariate analysis of covariance showed that the mental development index scores of the infants of mothers with prenatal exposure to SLEs in the first trimester averaged seven points (95% confidence interval 3.23-10.73 points) lower than those of the unexposed infants. Moreover, the infants in the exposed group achieved higher scores for regularity (adjusted mean [SD] 2.77 [0.65] vs. 2.52 [0.78], F(5,146) =5.27, p=0.023) and for persistence and attention span (adjusted mean 3.61 [0.72] vs. 3.35 [0.52], F(5,146) =5.51, p=0.020). INTERPRETATION: This study provides evidence that lower cognitive ability and less optimal worse behavioural response in infants might independently result from prenatal maternal stress.