Sally Ann Lederman

Prenatal exposure to PBDEs and neurodevelopment.

Background Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds that are persistent and bioaccumulative and therefore have become ubiquitous environment contaminants. Animal studies suggest that prenatal PBDE exposure may result in adverse neurodevelopmental effects. Objective In a longitudinal cohort initiated after 11 September 2001, including 329 mothers who delivered in one of three hospitals in lower Manhattan, New York, we examined prenatal PBDE exposure and neurodevelopment when their children were 12–48 and 72 months of age. Methods We analyzed 210 cord blood specimens for selected PBDE congeners and assessed neurodevelopmental effects in the children at 12–48 and 72 months of age; 118, 117, 114, 104, and 96 children with available cord PBDE measurements were assessed at 12, 24, 36, 48, and 72 months, respectively. We used multivariate regression analyses to evaluate the associations between concentrations of individual PBDE congeners and neurodevelopmental indices. Results Median cord blood concentrations of PBDE congeners 47, 99, and 100 were 11.2, 3.2, and 1.4 ng/g lipid, respectively. After adjustment for potential confounders, children with higher concentrations of BDEs 47, 99, or 100 scored lower on tests of mental and physical development at 12–48 and 72 months. Associations were significant for 12-month Psychomotor Development Index (BDE-47), 24-month Mental Development Index (MDI) (BDE-47, 99, and 100), 36-month MDI (BDE-100), 48-month full-scale and verbal IQ (BDE-47, 99, and 100) and performance IQ (BDE-100), and 72-month performance IQ (BDE-100). Conclusions This epidemiologic study demonstrates neurodevelopmental effects in relation to cord blood PBDE concentrations. Confirmation is needed in other longitudinal studies.

The Effects of the World Trade Center Event on Birth Outcomes among Term Deliveries at Three Lower Manhattan Hospitals

The effects of prenatal exposure to pollutants from the World Trade Center (WTC) disaster on fetal growth and subsequent health and development of exposed children remain a source of concern. We assessed the impact of gestational timing of the disaster and distance from the WTC in the 4 weeks after 11 September on the birth outcomes of 300 nonsmoking women who were pregnant at the time of the event. They were recruited at delivery between December 2001 and June 2002 from three hospitals close to the WTC site. Residential and work addresses of all participants for each of the 4 weeks after 11 September 2001 were geocoded for classification by place and timing of exposure. Average daily hours spent at each location were based on the women’s reports for each week. Biomedical pregnancy and delivery data extracted from the medical records of each mother and newborn included medical complications, type of delivery, length of gestation, birth weight, birth length, and head circumference. Term infants born to women who were pregnant on 11 September 2001 and who were living within a 2-mile radius of the WTC during the month after the event showed significant decrements in term birth weight (−149 g) and birth length (−0.82 cm), compared with infants born to the other pregnant women studied, after controlling for sociodemographic and biomedical risk factors. The decrements remained significant with adjustment for gestational duration (−122 g and −0.74 cm, respectively). Women in the first trimester of pregnancy at the time of the WTC event delivered infants with significantly shorter gestation (−3.6 days) and a smaller head circumference (−0.48 cm), compared with women at later stages of pregnancy, regardless of the distance of their residence or work sites from the WTC. The observed adverse effects suggest an impact of pollutants and/or stress related to the WTC disaster and have implications for the health and development of exposed children.

Relation between Cord Blood Mercury Levels and Early Child Development in a World Trade Center Cohort

Objective This study was designed to determine whether prenatal mercury exposure, including potential releases from the World Trade Center (WTC) disaster, adversely affects fetal growth and child development. Methods We determined maternal and umbilical cord blood total mercury of nonsmoking women who delivered at term in lower Manhattan after 11 September 2001, and measured birth outcomes and child development. Results Levels of total mercury in cord and maternal blood were not significantly higher for women who resided or worked within 1 or 2 miles of the WTC in the month after 11 September, compared with women who lived and worked farther away. Average cord mercury levels were more than twice maternal levels, and both were elevated in women who reported eating fish/seafood during pregnancy. Regression analyses showed no significant association between (ln) cord or maternal blood total mercury and birth outcomes. Log cord mercury was inversely associated with the Bayley Scales of Infant Development psychomotor score [Psychomotor Development Index (PDI)] at 36 months (b = –4.2, p = 0.007) and with Performance (b = –3.4, p = 0.023), Verbal (b = –2.9, p = 0.023), and Full IQ scores (b = –3.8, p = 0.002) on the Wechsler Preschool and Primary Scale of Intelligence, Revised (WPPSI-R), at 48 months, after controlling for fish/seafood consumption and other confounders. Fish/seafood consumption during pregnancy was significantly associated with a 5.6- to 9.9-point increase in 36-month PDI, and 48-month Verbal and Full IQ scores. Conclusions Blood mercury was not significantly raised in women living or working close to the WTC site in the weeks after 11 September 2001. Higher cord blood mercury was associated with reductions in developmental scores at 36 and 48 months, after adjusting for the positive effects of fish/seafood consumption during pregnancy.

Maternal Reporting of Prepregnancy Weight and Birth Outcome: Consistency and Completeness Compared with the Clinical Record

Objectives: We examined whether data obtained by maternal report could be used for research in clinical settings in place of abstraction of the clinical record. Method: Reported prepregnancy weight, delivery type, and infants birth date, birth weight, and length were compared to the same information from the clinical record. Results: Reported data, obtained from 198 women, were more complete than data in the 168 clinical records obtained. Prepregnancy weight from the clinical record was highly correlated with weight measured by us in early pregnancy, and with the value reported by the mother (differing significantly only in underweight women, who overreported by 2.4 lbs). There was complete concordance on birth date and method of delivery, and no significant differences in mean birth weight or length, between the reported and recorded information. Conclusion: The mothers report is a satisfactory substitute for clinical record data, being consistent with the record, and more complete, yet easier to obtain for clinical studies.

DNA Damage from Polycyclic Aromatic Hydrocarbons Measured by Benzo[a]pyrene-DNA Adducts in Mothers and Newborns from Northern Manhattan, The World Trade Center Area, Poland, and China

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 108 nucleotides), WTC (0.23 adducts per 108 nucleotides), Krakow (0.28 adducts per 108 nucleotides), Tongliang (0.31 adducts per 108 nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.

Body fat and water changes during pregnancy in women with different body weight and weight gain

Objective To determine the fat deposited during pregnancy in women gaining according to recommendations of the Institute of Medicine and the relationship of weight gain to fat gain in women of different starting weights (classified by their body mass index). Methods A cohort study of healthy, nonsmoking women, 18–36 years of age, identified during prenatal visits at three hospital clinics and one birthing center in New York City. From a pool of 432 eligible volunteers who signed a consent form, body composition measurements were performed on 200 women at weeks 14 (−2) and 37+ of pregnancy, and bone mineral mass was measured at 2–4 weeks postpartum. Body fat was estimated with a model that used total body water, weight, and density and bone mineral mass. Results In women gaining as recommended by the Institute of Medicine, fat gains during pregnancy for women underweight, normal weight, overweight, or obese before pregnancy were 6.0 ± 2.6 kg, 3.8 ± 3.4 kg, 3.5 ± 4.1 kg, and −0.6 ± 4.6 kg, respectively. Higher weight gain increased fat gain. Body water gain was not different among the four prepregnancy weight groups. Conclusion Recommended weight gain should not cause obesity in any weight group. Underweight women will normalize their body composition if they gain as recommended, whereas obese women will have little or no change in body fat. A majority of women do not gain as recommended during pregnancy.

Relationships among Polycyclic Aromatic Hydrocarbon–DNA Adducts, Proximity to the World Trade Center, and Effects on Fetal Growth

Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH–DNA adducts, or BaP–DNA adducts as their proxy, provide a measure of chemical-specific genetic damage that has been associated with increased risk of adverse birth outcomes and cancer. To learn whether PAHs from the WTC disaster increased levels of genetic damage in pregnant women and their newborns, we analyzed BaP–DNA adducts in maternal (n = 170) and umbilical cord blood (n = 203) obtained at delivery from nonsmoking women who were pregnant on 11 September 2001 and were enrolled at delivery at three downtown Manhattan hospitals. The mean adduct levels in cord and maternal blood were highest among newborns and mothers who resided within 1 mi of the WTC site during the month after 11 September, intermediate among those who worked but did not live within this area, and lowest in those who neither worked nor lived within 1 mi (reference group). Among newborns of mothers living within 1 mi of the WTC site during this period, levels of cord blood adducts were inversely correlated with linear distance from the WTC site (p = 0.02). To learn whether PAHs from the WTC disaster may have affected birth outcomes, we analyzed the relationship between these outcomes and DNA adducts in umbilical cord blood, excluding preterm births to reduce variability. There were no independent fetal growth effects of either PAH–DNA adducts or environmental tobacco smoke (ETS), but adducts in combination with in utero exposure to ETS were associated with decreased fetal growth. Specifically, a doubling of adducts among ETS-exposed subjects corresponded to an estimated average 276-g (8%) reduction in birth weight (p = 0.03) and a 1.3-cm (3%) reduction in head circumference (p = 0.04). The findings suggest that exposure to elevated levels of PAHs, indicated by PAH–DNA adducts in cord blood, may have contributed to reduced fetal growth in women exposed to the WTC event.

Pregnancy-Associated Obesity in Black Women in New York City

Objective: To determine weight gain during pregnancy and weight changes postpartum in first-time mothers delivering at or near term. Methods: At about 2 weeks after delivery, 47 adult, Black and Hispanic women provided information on their prepregnancy weight and height and maximum pregnancy weight. Women reinterviewed at 2 and 6 months after delivery reported their most recent weight measurement and the date of that measurement. This information was used to compute each womans prepregnancy body mass index, pregnancy weight gain, and weight loss postpartum. Information on infant feeding was also collected at each postpartum visit. Results: About 2/3 of the women and 100% of the overweight and obese women gained excessive weight during pregnancy. Weight gain was most marked in women who started pregnancy overweight or obese. At 2 months postpartum, women were on average almost 18 lb above their prepregnancy weight. No additional maternal weight was lost by 6 months postpartum. Most infants were started on formula by 2 weeks of age. At 2 months of age, 85% were fed formula only and 91% of the infants were on WIC. Conclusions: Our results demonstrate a need for interventions to help women avoid obesity by regulating their pregnancy weight gain, losing weight for a longer period postpartum, and initiating and maintaining exclusive breast-feeding.

Summary of the Presentations at the Conference on Preventing Childhood Obesity, December 8, 2003

Objective. Because of the rising rates of childhood obesity, we set out to determine what is known about its causes and what could be done to prevent additional increases. Methodology. A meeting was convened of experts in areas that bear on prevention of obesity development during intrauterine life, infancy, and very early childhood. They presented recent data and their interpretations of the stage of our current knowledge in related areas. They also proposed possible useful interventions and future directions for research. Findings. The speakers’ talks indicated that (1) breastfeeding as currently practiced seems to be significantly (albeit weakly) protective against obesity and should be encouraged as the preferred method of feeding infants for as long a duration as practical during the first year of life; (2) infant-feeding practices are changing in a way that may predispose to obesity (eg, soda and french fries are being fed to infants as young as 7 months of age), possibly altering taste preferences for foods and beverages that are energy dense and nutrient poor; (3) although little is known about parenting styles (eg, authoritative versus permissive), parenting style is likely to be a fruitful area of current research into childhood obesity etiology; and (4) the pattern of weight changes in the first few years of life may contribute to later risk of obesity. Conclusions. Children’s obesity will continue to be a growing problem unless we improve understanding of the key factors likely to be operative during intrauterine life, infancy, and very early childhood, identify those in whom intervention would have the greatest effect, design and evaluate preventive interventions, and promote those that are successful.

Relationship between polycyclic aromatic hydrocarbon-DNA adducts, environmental tobacco smoke, and child development in the World Trade Center cohort.

Background Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are air pollutants released by the World Trade Center (WTC) fires and urban combustion sources. BaP–DNA adducts provide a measure of PAH-specific genetic damage, which has been associated with increased risk of adverse birth outcomes and cancer. We previously reported that levels of BaP–DNA adducts in maternal and umbilical cord blood obtained at delivery were elevated among subjects who had resided within 1 mile of the WTC site during the month after 9/11; and that elevated blood adducts in combination with in utero exposure to environmental tobacco smoke (ETS) were significantly associated with decreased fetal growth. Objective Our aim was to assess possible effects of prenatal exposure to WTC pollutants on child development. Methods After 11 September 2001, we enrolled a cohort of nonsmoking pregnant women who delivered at three lower Manhattan hospitals. We have followed a subset of children through their third birthdays and measured cognitive and motor development using the Bayley-II Scales of Child Development (BSID-II). Results In multivariate analyses, we found a significant interaction between cord blood adducts and in utero exposure to ETS on mental development index score at 3 years of age (p = 0.02, n = 98) whereas neither adducts nor ETS alone was a significant predictor of (BSID-II) cognitive development. Conclusion Although limited by small numbers, these results suggest that exposure to elevated levels of PAHs in conjunction with prenatal ETS exposure may have contributed to a modest reduction in cognitive development among cohort children.