A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder.

BACKGROUND: We previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD. OBJECTIVES: In the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations. METHODS: This report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records. RESULTS: Children with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P = 0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P = 0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA. CONCLUSIONS: Higher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.

Behavioral Health Integration in a Medicaid Accountable Care Organization: Management Lessons from a Health Center.

Behavioral health integration, including as used in Medicaid Accountable Care Organizations, can improve care and decrease costs. Our model strives to integrate fully its medical, behavioral health, and substance use disorder services into one primary care clinic. Merged management has decreased wait times, improved billing, and enabled several promising innovations.

Maternal postpartum plasma folate status and preterm birth in a high-risk US population.

OBJECTIVE: While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB. DESIGN: Observational study. SETTING: Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.ParticipantsMother-infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24-72 h after delivery. RESULTS: Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3-5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB. CONCLUSIONS: If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.

Folate Nutrition Status in Mothers of the Boston Birth Cohort, Sample of a US Urban Low-Income Population.

OBJECTIVES: To examine maternal folic acid supplementation and plasma folate concentrations in the Boston Birth Cohort, a predominantly urban, low-income, minority population in Boston, Massachusetts. METHODS: This report includes 7612 mothers with singleton live births (3829 Black, 2023 Hispanic, 865 White, and 895 others) enrolled in the Boston Birth Cohort at the Boston Medical Center, during 1999 to 2014. Folic acid supplementation during preconception and each trimester was obtained via interview questionnaire. In a subset (n = 2598), maternal plasma folate concentrations were measured in blood samples drawn within a few days of delivery. RESULTS: The percentage of mothers taking folic acid supplementation almost daily during preconception and the first, second, and third trimesters were 4.3%, 55.9%, 59.4%, and 58.0%, respectively. Most striking, we observed a wide range of maternal plasma folate concentrations, with approximately 11% insufficient (< 13.4 nmol/L) and 23% elevated (> 45.3 nmol/L). CONCLUSIONS: Findings indicate that fewer than 5% of mothers in the Boston Birth Cohort started folic acid supplements before pregnancy, and approximately one third of mothers had either too low or too high plasma folate levels, which may have important health consequences on both the mother and the child.

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring.

BACKGROUND: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. METHODS: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. RESULTS: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). CONCLUSION: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.

Associations between gene polymorphisms in fatty acid metabolism pathway and preterm delivery in a US urban black population.

There is increasing evidence suggesting that higher intakes of fish or n-3 polyunsaturated fatty acids supplements may decrease the risk of preterm delivery (PTD). We hypothesized that genetic variants of the enzymes critical to fatty acids biosynthesis and metabolism may be associated with PTD. We genotyped 231 potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9 genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3) among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks gestation) and 568 mothers who delivered full-term babies (≥37 weeks gestation) at Boston Medical Center. After excluding SNPs that are in complete linkage disequilibrium or have lower minor allele frequency (<1%) or call rate (<90%), we examined the association of 206 SNPs with PTD using multiple logistic regression models. We also imputed 190 HapMap SNPs via program MACH and examined their associations with PTD. Finally, we explored gene-level and pathway-level associations with PTD using the adaptive rank truncated product (ARTP) methods. A total of 21 SNPs were associated with PTD (p value ranging from 0.003 to 0.05), including 3 imputed SNPs. Gene-level ARTP statistics indicated that the gene PTGES2 was significantly associated with PTD with a gene-based p value equal to 0.01. No pathway-based association was found. In this large and comprehensive candidate gene study, we found a modest association of genes in fatty acid metabolism pathway with PTD. Further investigation of these gene polymorphisms jointly with fatty acid measures and other genetic factors would help better understand the pathogenesis of PTD.

Faculty and resident attitudes about spirituality and religion in the provision of pediatric health care.

OBJECTIVE: To characterize pediatricians' attitudes toward spirituality/religion (S/R) in relationship to the practice of pediatrics. METHODS: Pediatric faculty (n = 100) and residents (n = 65) in an urban academic medical center completed a questionnaire about their attitudes toward and clinical practices related to S/R. Study variables included the strength of personal S/R orientation, attitudes toward S/R, clinicians' discussion of S/R with patients and families, self-reported S/R behaviors, the medical conditions that warrant discussion of S/R, and attitudes toward praying with patients if asked to do so. RESULTS: Sixty-five percent of pediatricians felt that faith plays a role in healing, and 76% reported feeling comfortable praying with a patient if asked to do so. Ninety-three percent would ask about S/R when discussing a life-threatening illness, and 96% when discussing death and dying. A strong personal S/R orientation was associated with beliefs that the pediatrician should discuss S/R with the patient (P <.01); beliefs that faith plays a role in healing (P <.01); and feelings that patients would like to discuss S/R with their pediatrician (P <.01), that the doctor-patient relationship would be strengthened by discussion of S/R (P <.01), and that physicians should call on an S/R leader for an illness or death (P <.01). Personal S/R orientation was not related to whether physicians reported that they discuss S/R issues with their patients (P =.08). Residents were more likely than faculty to state that it is appropriate to pray with patients if asked to do so (P <.05), and compared with pediatricians who were science majors in college, pediatricians who were nonscience majors in college felt more comfortable praying with patients if asked to do so (P <.01). CONCLUSIONS: In an urban, inner-city, academic medical center, pediatric residents and faculty have an overall positive attitude toward the integration of S/R into the practice of pediatrics.