Martin Kharrazi

Juggling Work and Breastfeeding: Effects of Maternity Leave and Occupational Characteristics

OBJECTIVES. Juggling breastfeeding and paid work can challenge breastfeeding success. We examined the relationship between breastfeeding and maternity leave before and after delivery among working mothers in Southern California. California is 1 of only 5 states in the United States providing paid pregnancy leave that can be extended for infant bonding. PATIENTS AND METHODS. Drawing from a case-control study of preterm birth and low birth weight, 770 full-time working mothers were compared on whether they established breastfeeding in the first month. For those who established breastfeeding, we examined duration. Eligible women participated in Californias Prenatal Screening Program; delivered live births between July 2002 and December 2003; were ≥18 years old; had a singleton birth without congenital anomalies; and had a US mailing address. We assessed whether maternity leave and other occupational characteristics predicted breastfeeding cessation and used multivariate regression models weighted for probability of sampling to calculate odds ratios for breastfeeding establishment and hazards ratios for breastfeeding cessation. RESULTS. A maternity leave of ≤6 weeks or 6 to 12 weeks after delivery was associated, respectively, with a fourfold and twofold higher odds of failure to establish breastfeeding and an increased probability of cessation after successful establishment, relative to women not returning to work, after adjusting for covariates. The impact of short postpartum leave on breastfeeding cessation was stronger among nonmanagers, women with inflexible jobs, and with high psychosocial distress. Antenatal leave in the last month of pregnancy was not associated with breastfeeding establishment or duration. CONCLUSIONS. Postpartum maternity leave may have a positive effect on breastfeeding among full-time workers, particularly those who hold nonmanagerial positions, lack job flexibility, or experience psychosocial distress. Pediatricians should encourage patients to take maternity leave and advocate for extending paid postpartum leave and flexibility in working conditions for breastfeeding women.

Environmental tobacco smoke and pregnancy outcome.

Background: Recent reviews conclude that environmental tobacco smoke (ETS) leads to diminished birth weight. However, the threshold and magnitude of that effect is uncertain. We aimed to determine the magnitude and shape of the relations between ETS and various adverse pregnancy outcomes using a highly sensitive biochemical assay. Methods: Maternal serum specimens were collected from more than 3000 women enrolled in Californias prenatal screening program in 1992 and analyzed for cotinine. Information on pregnancy outcomes was obtained from live birth/fetal death records and hospital questionnaires. We conducted analyses on 2777 woman–live birth pairs and 19 woman–fetal death pairs in which the mother was presumed to be a nonsmoker (midtrimester cotinine levels ≤10 ng/mL). Results: In multiple logistic regression analyses, the odds ratios of fetal death, preterm delivery, and term-low birth weight were 3.4, 1.8, and 1.8, respectively, in the highest cotinine quintile (0.236–10 ng/mL), compared with the lowest quintile (<0.026 ng/mL). In adjusted linear models, there was a linear dose-dependent effect of log cotinine on mean birth weight (−109 g) and mean infant length (−0.84 cm) over the range of cotinine values. Linear relations were not found with respect to infant head circumference or the ratio of brain weight to body weight. Infants body mass index declined with exposures above approximately 0.5 ng/mL cotinine. We estimated that ETS levels at or above 0.05 ng/mL (experienced by 62% of the study population) accounted for 12% of all adverse outcomes. Conclusions: ETS exposure in pregnant women adversely affects pregnancy by increasing fetal mortality and preterm delivery at higher exposure levels and slowing fetal growth across all levels of ETS exposure.

Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study

BackgroundImmune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.MethodsUsing Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.ResultsElevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.ConclusionThe profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.

Maternal Mid-Pregnancy Autoantibodies to Fetal Brain Protein: The Early Markers for Autism Study

BACKGROUND Immune dysfunction has been associated with autism, yet whether maternal immune status during pregnancy plays a causal role remains to be clarified. METHODS We conducted a population-based case-control study nested within the cohort of infants born July 2000-September 2001 to women who participated in the prenatal screening program in Orange County, California. Cases (AU; n = 84) were children receiving services for autism at the Regional Center of Orange County. Two control groups were included: children with mental retardation or developmental delay (MR; n = 49) receiving services at the same regional center; and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (GP; n = 160). Maternal autoantibody reactivity to fetal brain protein was measured by Western blot in archived mid-pregnancy blood specimens drawn during routine prenatal screening. Presence of specific bands and band patterns were compared between the three study groups. RESULTS The pattern of maternal mid-gestation antibody reactivity to human fetal brain protein varied by study group and by autism onset type, although most differences did not reach statistical significance. Reactivity to a band at 39 kDa was more common among mothers of children with autism (7%) compared with mothers of MR (0%; p = .09) and GP control subjects (2%; p = .07), and simultaneous reactivity to bands at 39 kDa and 73 kDa was found only in mothers of children with early onset autism (n = 3). CONCLUSIONS Our findings indicate that further studies of prenatal immune markers might be a productive area for etiologic and biologic marker discovery for autism.

Use of Screening Dried Blood Spots for Estimation of Prevalence, Risk Factors, and Birth Outcomes of Congenital Cytomegalovirus Infection

OBJECTIVES To determine the birth prevalence of cytomegalovirus (CMV) in a population-based sample of newborns by use of dried blood spots compared with previous studies that used established detection methods, and to evaluate risk factors and birth outcomes for congenital CMV infection. STUDY DESIGN A total of 3972 newborn dried blood spots collected for the California Newborn Screening Program were tested for presence of CMV DNA. Demographic and pregnancy data were obtained from linked newborn screening and live-birth records. RESULTS CMV prevalence among newborns by maternal race and ethnicity was 0.9% for blacks, 0.8% for Hispanics, 0.6% for whites, and 0.6% for Asians. Among Hispanics (n = 2053), infants who were infected had younger mothers (23 vs 26 years, P = .03), and prevalence was higher for children with no father information provided (2.6% vs 0.6%, P = .03). Overall CMV infection was associated with low birth weight (prevalence ratios [95% CI]: 3.4 [1.4-8.5]) and preterm birth (2.7 [1.4-5.1]). CMV viral loads were inversely related to birth weight and gestational age (both P = .03). CONCLUSIONS CMV prevalence measured with dried blood spots was similar to reports using standard viral culture methods. Dried blood spots may be suitable for detection of CMV infection in newborns and warrant further evaluation. Congenital CMV infection may contribute to low birth weight and preterm birth.

Estimation of environmental tobacco smoke exposure during pregnancy using a single question on household smokers versus serum cotinine

Environmental tobacco smoke (ETS) exposure has been studied in relation to many diseases. The ability of a study to find an association between exposure and disease is, in part, determined by the accuracy of the exposure measure. This study examined how accurately one question, the number of smokers in the household, asked at birth, predicts ETS exposure in pregnant nonsmokers as assessed by serum cotinine. Blood specimens, drawn at 15–19 weeks gestation, from 783 women who participated in a prenatal screening program in California in 1992 were analyzed for cotinine. Serum cotinine was significantly correlated with the number of smokers in the household (r=0.35, P<0.001, geometric mean cotinine (nanograms per milliliter) for 0 smokers=0.06, 1 smoker=0.18, 2 or more smokers=0.29). Using multiple regression, the number of smokers in the household accounted for 11% of the variation in serum cotinine. Cotinine concentrations were twice as high in women living with one or more smokers compared to women not living with a smoker, when reported exposure (0 or >0h) at home, work and other places was similar. Thus, the number of household smokers can account for a statistically significant amount of variation in serum cotinine and omission of this information would result in an underestimation of ETS exposure. Although use of this question alone does not provide an adequate estimation of ETS exposure as determined by serum cotinine, the results of this study indicate that this question is an important component of assessing ETS exposure.

Brain‐derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study

To investigate levels of brain‐derived neurotrophic factor (BDNF) in mid‐pregnancy and neonatal blood specimens as early biologic markers for autism, we conducted a population‐based case–control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, CA. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid‐pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead‐based assay (Luminex, Biosource Human BDNF Antibody Bead Kit, Invitrogen‐Biosource, Carlsbad, CA). The concentration of BDNF in maternal mid‐pregnancy and neonatal specimens was similar across all three study groups. These data do not support previous findings of an association between BDNF and autism and suggest that the concentration of BDNF during critical periods of early neurodevelopment is not likely to be a useful biomarker for autism susceptibility.

Newborn Screening for Cystic Fibrosis in California

OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California. METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values ≥62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with ≥2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling. RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test–positive infants, respectively). CONCLUSIONS: The 3-step model had high detection and low false-positive levels in this diverse population.

Maternity Leave In The Ninth Month of Pregnancy and Birth Outcomes Among Working Women

PURPOSE The health effects of antenatal maternity leave have been scarcely evaluated. In California, women are eligible for paid benefits up to 4 weeks before delivery. We explored whether leave at > or =36 weeks gestation increases gestation and birthweight, and reduces primary cesarean deliveries among full-time working women. METHODS Drawing from a 2002--2003 nested case-control study of preterm birth and low birthweight among working women in Southern California, we compared a cohort of women who took leave (n = 62) or worked until delivery (n = 385). Models weighted for probability of sampling were used to calculate hazards ratios for gestational age, odds ratios (OR) for primary cesarean delivery, and multilinear regression coefficients for birthweight. MAIN FINDINGS Leave-takers were similar to non-leave-takers on demographic and health characteristics, except that more clerical workers took leave (p = .02). Compared with non-leave-takers, leave-takers had almost 4 times lower odds of cesarean delivery after adjusting for covariates (OR, 0.27; 95% confidence interval [CI], 0.08-0.94). Overall, there were no marked differences in length of gestation or mean birthweight. However, in a subgroup of women whose efforts outstripped their occupational rewards, gestation was prolonged (hazard ratio for delivery each day between 36 and 41 weeks, 0.56; 95% CI, 0.34-0.93). CONCLUSION Maternity leave in late pregnancy shows promise for reducing cesarean deliveries and prolonging gestation in occupationally strained women.

Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability

Background: Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are neurodevelopmental toxicants, but few studies have examined associations with autism spectrum disorder (ASD). Objectives: We aimed to determine whether prenatal exposure to PCBs and OCPs influences offspring risk of ASD and intellectual disability without autism (ID). Methods: We conducted a population-based case–control study among Southern California births, including children with ASD (n = 545) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR) criteria and ID (n = 181), as well as general population (GP) controls (n = 418). Concentrations of 11 PCB congeners and 2 OCPs measured in banked second-trimester serum samples were compared between the diagnostic groups. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses. Results: Geometric mean levels of several PCB congeners were higher in the ASD group than in the ID and GP groups. ASD risk was elevated for a number of PCB congeners, particularly for the highest vs. lowest quartile of PCB138/158 (AOR = 1.79; 95% CI: 1.10, 2.71) and PCB153 (AOR = 1.82; 95% CI: 1.10, 3.02), and for highest deciles of other congeners in secondary analyses. PCB138/158 was also associated with increased ID (AOR = 2.41; 95% CI: 1.18, 4.91), though no trend was suggested. OCPs were not associated with increased risk of ASD in primary analyses, whereas nonmonotonic increases in risk of ID were found with p,p´-DDE. Conclusions: Our results suggest higher levels of some organochlorine compounds during pregnancy are associated with ASD and ID. Citation: Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, Windham GC. 2017. Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect 125:474–480; http://dx.doi.org/10.1289/EHP277