Preconception Vitamin Research Articles

Effect of pre-conception serum vitamin D level on pregnancy outcomes in women undergoing in vitro fertilization with fresh embryo transfer: a retrospective analysis

BackgroundThis study aims to investigate the association of pre-conception vitamin D levels on adverse pregnancy outcomes in women undergoing in vitro fertilization with fresh embryo transfer.MethodsThis was a retrospective cohort study using archived serum 25-hydroxyvitamin D measured in the pre-conception period before ovarian stimulation in patients undergoing in vitro fertilization with fresh autologous embryo transfer. A total of 306 women were included and adverse pregnancy outcomes in their resulting pregnancy were recorded. Patients who were vitamin D deficient (< 20ng/ml) were compared with those who were non-deficient (≥20ng/ml) and analysed for any association with adverse pregnancy outcomes.ResultsA total of 16/306 (5.3%) patients had hypertensive disorders of pregnancy (gestational hypertension and/or pre-eclampsia). The adjusted odds ratio for hypertensive disorders of pregnancy using vitamin D deficiency as a reference was 0.190 (95% CI 0.042–0.852) (p = 0.030). Other pregnancy complications were not significantly different with regards to pre-conception vitamin D status.ConclusionsPre-conception vitamin D deficiency is associated with an increased risk of hypertensive disorders in pregnancy in women undergoing in vitro fertilization with fresh embryo transfer.Trial registrationHKUCTR 2361 (9th March 2018).

Effects of preconceptional vitamin D levels on in vitro fertilization outcomes in infertile patients with polycystic ovary syndrome: A retrospective cohort study.

Vitamin D plays various roles in different stages of reproduction, and abnormalities in its levels are associated with diseases such as polycystic ovary syndrome (PCOS). This study aimed to determine the relationship between initial vitamin D levels and in vitro fertilization (IVF) outcomes in PCOS patients. This retrospective cohort study included 1174 PCOS patients who consulted the Acıbadem Maslak Hospital IVF Clinic between January 2015 and March 2021. We investigated the effect of preconceptional vitamin D levels on IVF outcomes using data analysis with SigmaPlot 14.5. We found a significant positive correlation between preconceptional vitamin D levels and positive clinical pregnancy rates (p < 0.001) as well as increased endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day (p < 0.001, r = 0.262). The optimal vitamin D cut-off value for predicting positive hCG test results was identified as 13.24 ng/mL, as determined by receiver operating characteristic curve analysis (sensitivity = 0.839, specificity = 0.677). No association was observed with other IVF outcome parameters, miscarriage rates, or clinical pregnancy rates based on EMT. The study suggests that PCOS patients with vitamin D levels above 13.24 ng/mL are more likely to achieve positive hCG results after IVF. These findings highlight the potential importance of vitamin D supplementation in improving pregnancy outcomes for PCOS patients. Additionally, increased EMT on hCG day may explain the higher clinical pregnancy rates associated with elevated vitamin D levels.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach

To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05-1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00-1.99; male aRR, 1.51; 95% CI, 1.01-2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95-1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00-1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

Preconception vitamin D and miscarriage in a prospective cohortstudy.

Is preconception vitamin D level associated with the risk of miscarriage? Preconception vitamin D levels are not associated with the risk of miscarriage in a population of women conceiving naturally. In humans, low vitamin D has been associated with prolonged menstrual cycles, delayed ovulation and a lower probability of conception. Animal and in vitro data indicate that vitamin D may affect implantation. This prospective time-to-pregnancy study included 362 women who were trying to conceive naturally between 2008 and 2015. This study included participants who had been trying to conceive naturally for 3 months or less at enrollment and aged 30-44 years. A preconception blood sample was collected and 25-hydroxyvitamin D [25(OH)D] was measured. Women who conceived (N = 362) were at risk of a miscarriage from the day of a reported positive pregnancy test until either a participant-reported pregnancy loss or 20 weeks post day of last menstrual period, whichever came first. Gestational age was defined by ovulation. Time to miscarriage (days) or censoring was modeled using a multivariate Cox proportional hazards model. Multiple imputation was performed for missing covariates and missing day of ovulation. The mean age was 33 years (SD: 3.0 years). Mean 25(OH)D was lower among those who reported their race as African-American and those with a higher BMI. After adjustment for age, race, BMI, education, exercise, alcohol and caffeine intake, compared to the referent group (30-<40 ng/ml), the hazard ratio (HR) and 95% CI for those with a low 25(OH)D level (<30 ng/ml) was 1.10 (CI: 0.62, 1.91). Among participants with a higher 25(OH)D level (≥40 ng/ml), the HR was 1.07 (CI: 0.62, 1.84). This study was limited by a 25(OH)D measurement at only a single time point. A large percentage of women in this study had sufficient vitamin D levels, which may have limited our power to detect an effect of deficiency. Women in this study were older (30-44 years), and predominantly reported their race as White which may limit generalizability. The findings of this study do not suggest an association between preconception vitamin D and miscarriage. Future research should focus on women at greater risk for miscarriage or in populations at risk for vitamin D deficiency or on supplementation. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01ES103333). This research was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683. The authors have no conflicts of interest. N/A.

Preconception vitamin D intake and obstetric outcomes in women using assisted reproductive technology: the Japan Environment and Children’s Study

BackgroundIn reproductive medicine, vitamin D (VitD) is of particular interest because its deficiency has been linked to various infertility issues. Thus, preconception care, including appropriate VitD supplementation, is essential, especially in women using assisted reproductive technology (ART). Despite the therapeutic benefits of VitD, adverse events due to a high daily intake may influence obstetric outcomes. However, the effects of either low or high preconception VitD intake on obstetric outcomes, including the outcomes in women who used ART, remain unclear. Therefore, the aim of this study was to examine the association between pre-pregnancy daily VitD intake and obstetric outcomes in Japanese women, including those who conceived through ART.MethodsData were obtained from the Japan Environment and Children’s study database comprising 92,571 women recruited between January 2011 and March 2014 in Japan. Participants were categorized into five quintiles according to pre-pregnancy VitD intake (Q1 and Q5 had the lowest and highest VitD intake, respectively) and stratified according to the use of ART. Multiple logistic regression was performed to identify the effects of pre-pregnancy VitD intake on preterm birth (PTB), low-birth weight infant (LBW), and small for gestational age (SGA).ResultsUsing Q3 (middle VitD intake) as a reference, our analysis revealed that Q5 (highest VitD intake) showed an increased risk of LBW < 1500 g (adjusted odds ratio [aOR]: 1.09, 95% confidence interval [CI]: 1.00–1.18) and SGA (aOR: 1.26, 95% CI: 1.14–1.39) among women who conceived without ART. Among women who conceived with ART, we found that Q5 (highest VitD intake) showed an increased risk of PTB at < 37 weeks (aOR: 2.05, 95% CI: 1.27–3.31).ConclusionThe present study revealed that higher VitD intake before pregnancy may affect perinatal outcomes, particularly in women using ART. Our findings may facilitate personalized preconceptional counseling regarding VitD intake based on the method of conception, especially among women using ART.

Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial.

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.

Maternal Vitamin D level and Early Pregnancy Loss A Nested Case Control Study

Objective: To assess the role of vitamin D deficiency and early pregnancy loss.Patient and Method: A nested case control study conducted in outpatient antenatal care clinic under supervision of Ain Shams University Maternity hospital from the period of March 2020 to June2020. Pregnant ladies in the first trimester were screened for eligibility criteria.Blood samples were taken from the participants at thetime of presentation. All participants were followed till the end of thefirst trimester to report cases of miscarriage. Vitamin d was assessedfor the 40 women who suffered from miscarriage (cases) and for 40selected controls.The primary outcome was the relation between vitamin d level and early pregnancy loss. Secondary outcome was therelation between vitamin d deficiency and obesity.Results: Our findings showed that the miscarriage groupwas significantly olderthan control group as p (42.5%) had 25(OH)D deficiency while (40.0%)&(17.5%) of caseshad either 25(OH)D insufficiencyor sufficiency which significantlydifferent than control group (p=0.049).25(OH)D ≤24.5 (ng/mL) wasa significant factor that increased the likelihood of first-trimestricmiscarriage with sensitivity 80%.No significant differences according to BMI grades regarding 25(OH)D grades.Conclusion: Vitamin d deficiency is one of modifiable risk factors forfirst trimestric abortion. . Preconceptional vitamin D supplementationis an easy method for decreasing incidence of early pregnancy loss.

Vitamin D levels in women of reproductive age group- where do we stand?

Vitamin D is a steroid hormone which is fat soluble and activated in kidneys. It plays multiple roles including regulation of cellular growth and differentiation, metabolic modifications, immunity, insulin resistance, cardiovascular disease, malignancies and also various reproduction related states like preeclampsia, preterm birth and gestational diabetes, along with calcium and phosphorous regulation in the body. In present study, we analyzed serum vitamin D levels in 100 women of reproductive age group (15-45 years). Surprisingly, only 7% of the women were found to have sufficient vitamin D level while 19% had insufficient level and 74 % were deficient. Such alarming community wide deficiency raises concern. Especially in this reproductive age group the women are liable to have rickets, osteoporosis, osteomalacia, low fertility and increased risk for adverse pregnancy outcomes. Pre-conception vitamin D supplementation is simple, easy, and inexpensive method which can prevent such grave outcomes. Keywords: Vitamin D, Women, Reproductive age group, Deficiency.

Preconception Vitamin D Status and Offspring Sex Ratio Among Women with Prior Pregnancy Loss (OR17-05-19)

ObjectivesExperimental data indicate that maternal exposure to factors known to alter inflammatory milieu may be specifically harmful to the conception or survival of male fetuses. Indeed, in a recent clinical trial, preconception administration of low dose aspirin versus placebo restored the skewed sex ratio at birth among women with elevated inflammation, providing direct evidence of this phenomenon in humans. However, it is unknown whether other factors associated with inflammation, such as vitamin D status, are associated with offspring sex ratio at birth. Our objective was thus to evaluate the association of preconception serum 25-hydroxyvitamin D levels [25(OH)D] and male live birth among 1228 reproductive-age women with a history of 1–2 prior losses who were enrolled in the Effects of Aspirin in Gestation and Reproduction trial between 2007–2011. MethodsWe estimated RRs and 95% CIs for male live birth according to 25(OH)D sufficiency (≥75 vs. <75 nmol/L) using generalized estimating equations of log-binomial regression with robust standard errors. ResultsAmong the 1086 women who completed follow-up, the proportion of live-born males was 24% (n = 136) and 30% (n = 156) in the 25(OH)D insufficient and sufficient groups, respectively. After adjustment for age, race/ethnicity, and other factors, women in the 25(OH)D sufficient group were 23% (95% CI: 1.01, 1.49) more likely to have a live-born male infant compared to the insufficient group. Associations were stronger among women with elevated versus low levels of high sensitivity C-reactive protein (>1.95 ng/mL: RR: 1.41; 95% CI: 0.99, 2.00 versus ≤1.95 ng/mL RR: 1.11; 95% CI: 0.88, 1.41), a marker of systemic low-grade inflammation. ConclusionsPreconception vitamin D status was associated with male live birth, particularly among women with low-grade inflammation. These data suggest that maternal vitamin D sufficiency may mitigate maternal inflammation that would otherwise be detrimental to male fetal survival. Funding SourcesIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.

The earlier the better: preconception vitamin D and protection against pregnancy loss

The earlier the better: preconception vitamin D and protection against pregnancy loss

Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study

Vitamin D deficiency during pregnancy is associated with adverse pregnancy outcomes, although the association between preconception vitamin D concentrations and livebirth is unknown. We aimed to assess the association between preconception vitamin D and pregnancy outcomes among women with proven fecundity. We did a secondary analysis of a prospective cohort from the block-randomised, double-blind, placebo-controlled EAGeR trial. Women aged 18-40 years with one to two previous pregnancy losses were recruited from June 15, 2007, to July 15, 2011, at four clinical sites in the USA and followed up for up to six menstrual cycles while attempting pregnancy and throughout pregnancy if they conceived. Serum 25-hydroxyvitamin D was measured at baseline (preconception) and 8 weeks of gestation. Outcomes of interest included clinical pregnancy, time to pregnancy, pregnancy loss, and livebirths. Risk ratios (RRs) and 95% CIs for livebirths, pregnancy, and pregnancy loss were estimated with weighted log-binomial regression. To assess time to pregnancy, we used discrete time Cox proportional hazards models to calculate fecundability odds ratios (FORs) with 95% CIs. EAGeR is registered with ClinicalTrials.gov, number NCT00467363. 1191 women had available data on preconception 25-hydroxyvitamin D concentrations. 555 (47%) women were classified as having sufficient concentrations (≥75 nmol/L) and 636 (53%) as having insufficient concentrations (<75 nmol/L). Women with sufficient preconception 25-hydroxyvitamin D were more likely to achieve clinical pregnancy (adjusted RR 1·10 [1·01-1·20]) and livebirth (1·15 [95% CI 1·02-1·29]) than were women with insufficient concentrations. Among women who achieved pregnancy, sufficient preconception 25-hydroxyvitamin D, but not that at 8 weeks of gestation, was associated with reduced risk of pregnancy loss (preconception RR per 25 nmol/L 0·88 [95% CI 0·77-0·99]; 8 weeks of gestation 0·98 [0·95-1·01]). No association was observed with fecundability in women with sufficient versus those with insufficient preconception 25-hydroxyvitamin D concentrations (adjusted FOR 1·13 [95% CI 0·95-1·34]). Sufficient preconception 25-hydroxyvitamin D (≥75 nmol/L) was associated with increased likelihood of pregnancy and livebirth. Increased vitamin D concentrations before conception, but not in early pregnancy, were associated with reduced pregnancy loss. National Institutes of Health and Doris Duke Charitable Foundation.

Vitamin D deficiency is associated with poor reproductive outcomes in PCOS but not unexplained infertility

The impact of vitamin D deficiency on the success of ovulation induction (OI) cycles and the risk pregnancy complications after OI has not been extensively investigated. The goal of this study was to evaluate the relationship between preconception vitamin D status and reproductive outcomes in women with a diagnosis of either PCOS or unexplained infertility treated with OI.

Making birth defects ‘preventable’: Pre-conceptional vitamin supplements and the politics of risk reduction

Since the mid-1990s, governments and health organizations around the world have adopted policies designed to increase women’s intake of the B-vitamin ‘folic acid’ before and during the first weeks of pregnancy. Building on initial clinical research in the United Kingdom, folic acid supplementation has been shown to lower the incidence of neural tube defects (NTDs). Recent debate has focused principally on the need for mandatory fortification of grain products with this vitamin. This article takes a longer view, tracing the transformation of folic acid from a routine prenatal supplement to reduce the risk of anaemia to a routine ‘pre-conceptional’ supplement to ‘prevent’ birth defects. Understood in the 1950s in relation to social problems of poverty and malnutrition, NTDs were by the end of the century more likely to be attributed to individual failings. This transition was closely associated with a second. Folic acid supplements were initially prescribed to ‘high-risk’ women who had previously borne a child with a NTD. By the mid-1990s, they were recommended for all women of childbearing age. The acceptance of folic acid as a ‘risk-reducing drug’ both relied upon and helped to advance the development of preventive and clinical practices concerned with women’s health before pregnancy.

Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis

Data on pregnancy outcomes among women with psoriasis are lacking. However, there are several known comorbidities of psoriasis, including obesity, smoking and depression, each of which increases the risk for negative birth outcomes. To determine if pregnant women with psoriasis have an excess of potentially modifiable risk factors for adverse pregnancy outcomes. Prospectively collected data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project were analysed to compare the prevalence of selected risk factors between 170 pregnant women with psoriasis and 158 nondiseased controls. Women with psoriasis were more likely to be overweight/obese prior to pregnancy (P < 0.0001), to smoke (P < 0.0001), or to have a diagnosis of depression (P = 0.03), and were less likely to have been taking preconceptional vitamin supplements (P = 0.004). After controlling for race/ethnicity and socioeconomic status, women with psoriasis were 2.37 (95% confidence interval 1.45-3.87) times more likely to be overweight/obese as women without psoriasis. Duration of disease, age at onset, measures of disease impact during pregnancy, or use of biologics in pregnancy were not significant predictors of overweight/obesity in the subset of psoriatic women. Pregnant women with psoriasis may be at increased risk for adverse pregnancy outcomes due to comorbidities or other health behaviours associated with the disease. These should be taken into consideration during clinical treatment of women with psoriasis who are in their childbearing years.

Establishment of a Low Birth Weight Registry and Initial Outcomes

The study was conducted to evaluate a regional, prospective database of information on mothers of low birth weight (LBW) infants. The database informs on unidentified or under-reported modifiable risk factors from which evidence-based, targeted community intervention strategies could be designed to lower the rate of low birth weight in the region. The LBW Registry is based on informed consent, a semi-structured face-to-face (FTF) interview with the mother of the newborn LBW infant, medical record review, and birth certificate worksheet data collection. Descriptive statistics were used to summarize data from the registry. High rates of modifiable risk factors among mothers of low birth weight infants (October 2007-October 2008) include smoking (44%), alcohol consumption (16%), and drug abuse (14%). Preconception vitamin use was low (34%). The reported use of fertility drugs in FTF interviews was notably higher than information reported on the birth certificate worksheets by the same set of interviewed mothers (5.4 vs. 1.5%), as was alcohol use during pregnancy (16 vs. 1.3%). More than half (52%) of the mothers of low birth weight infants reported a vaginal or urinary tract infection during pregnancy. Additionally there were higher than average rates of unmarried mothers (62%), unintended pregnancies (67%), and Medicaid beneficiaries (57%). Mothers repeatedly expressed excessive demands in their lives, straining their coping abilities and resources. The LBW Registry provides expanded local data on potentially modifiable risk factors to aid in designing targeted prevention and intervention strategies.

Preconceptional vitamin use decreases neural tube defects

Preconceptional vitamin use decreases neural tube defects

Prevention of neural tube defects in curly-tail mice by maternal administration of vitamin A.

AbstractVarious doses of vitamin A were administered on day 9 of pregnancy to the pregnant curly‐tail mouse, a mutant, 60 per cent of which have neural tube defects (NTD). There was a reduction in the incidence of NTD in the fetuses with all doses used. The effect was maximal with 5 mg/kg; it was also marked, but to a lesser degree, with 10 and 20 mg/kg and minimal with 1 mg/kg. The implications of these findings in the mouse to the prevention of NTD in humans by preconception vitamin supplementation are discussed.