Gertrud S. Berkowitz

Prenatal Phenol and Phthalate Exposures and Birth Outcomes

BACKGROUND Many phthalates and phenols are hormonally active and are suspected to alter the course of development. OBJECTIVE We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. METHODS We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. RESULTS Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. CONCLUSIONS We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.

Delayed childbearing and the outcome of pregnancy.

Whether women who delay childbearing are at increased risk for adverse outcomes of pregnancy is of concern because of the growing proportion of first births to older women. We assessed the effect of advancing maternal age on the outcome of pregnancy in first births in a hospital-based cohort study of 3917 private patients who were 20 years of age or older with a singleton gestation. There was a slight elevation in the risk of having a low-birth-weight infant among women who were 35 years of age or older (adjusted odds ratio, 1.3; 95 percent confidence interval, 0.9 to 1.9) as compared with the risk among women 20 to 29 years of age. However, there was no evidence that women between 30 and 34 or those 35 and older had an increased risk of having a preterm delivery or of having an infant who was small for gestational age, had a low Apgar score, or died in the perinatal period. In contrast, even after controlling for sociodemographic and medical risk factors, we found that women who were 35 or older were significantly more likely to have specific antepartum and intrapartum complications and those who were 30 or older were significantly more likely to have both cesarean sections and infants who were admitted to the newborn intensive care unit. This study suggests that although older primiparous women have higher rates of complications of pregnancy and delivery, their risk of a poor neonatal outcome is not appreciably increased.

Pregnancy outcome at age 40 and older

Objective To examine pregnancy outcome among women age 40 years and older. Methods A retrospective cohort study, including 1404 pregnant women at least 40 years of age and 6978 controls age 20–29 years, was conducted. The two groups were stratified, according to parity, to facilitate separate analysis. Associations between maternal age and pregnancy outcomes were assessed with the contingency χ2 or two-tailed Fisher exact test. Multiple logistic regression was used to evaluate these associations and allowed for calculation of adjusted odds ratios (OR). Results Older gravidas were more likely to develop gestational diabetes (nulliparas: OR 2.7,95% confidence interval [CI] 1.9–3.7; multiparas: OR 3.8, 95% CI 2.7–5.4), preeclampsia (nulliparas: OR 1.8, 95% CI 1.3–2.6; multiparas: OR 1.9, 95% CI 1.2–2.9), and placenta previa (nulliparas: OR 13.0, 95% CI 4.8–35.0; multiparas: OR 6.4, 95% CI 2.6–15.6). Older women were also at increased risk for cesarean delivery (nulliparas: OR 3.1, 95% CI 2.6–3.7; multiparas: OR 3.3, 95% CI 2.6–4.1), operative vaginal delivery (nulliparas: OR 2.4, 95% CI 1.9–2.9; multiparas: OR 1.5, 95% CI 1.2–1.9), and induction of labor (nulliparas: OR 1.5, 95% CI 1.2–1.8; multiparas: OR 1.4, 95% CI 1.1–1.7). Older nulliparas had an increased incidence of abnormal labor patterns (OR 1.4, 95% CI 1.2–1.7), neonatal intensive care unit admissions (OR 1.6, 95% CI 1.2–2.2), and low l-minute Apgar scores (OR 2.3, 95% CI 1.1–4.9). Older multiparas were more likely to experience fetal distress (OR 2.0, 95% CI 1.4–2.8), antepartum vaginal bleeding (OR 1.8, 95% CI 1.1–3.1), and preterm premature rupture of membranes (OR 1.7, 95% CI 1.1–2.9). Conclusion Although maternal morbidity was increased in the older gravidas, the overall neonatal outcome did not appear to be affected.

Environmental Toxins and Breast Cancer on Long Island. I. Polycyclic Aromatic Hydrocarbon DNA Adducts

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels compared with the lowest was 1.51 [95% confidence interval (CI), 1.04-2.20], with little or no evidence of substantial confounding (corresponding multivariate-adjusted OR, 1.49; 95% CI, 1.00-2.21). There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect.

Risk factors for preterm birth subtypes.

To assess epidemiologic risk factors for preterm birth subcategories in an urban population, we undertook a study of 31,107 singleton livebirths that took place at Mount Sinai Hospital in New York City between 1986 and 1994. We subdivided the preterm births into preterm premature rupture of the membranes, preterm labor, and medically induced births. We obtained information regarding the preterm subtypes and their epidemiologic risk factors from a computerized perinatal database. Adjusted odds ratios showed an increased risk for all three preterm birth subtypes in women who were black (1.9 for preterm premature rupture of membranes, 2.1 for preterm labor, and 1.7 for medically induced births) or Hispanic (1.7 for preterm premature rupture of membranes, 1.9 for preterm labor, and 1.6 for medically induced births), those who had had a previous preterm birth (3.2 for preterm premature rupture of membranes, 4.5 for preterm labor, and 3.3 for medically induced births), those who began prenatal care after the first trimester (1.4 for preterm premature rupture of membranes, 1.3 for preterm labor, and 1.3 for medically induced births), women who had been exposed to diethylstilbestrol in utero (3.1 for preterm premature rupture of membranes, 4.1 for preterm labor, and 3.7 for medically induced births), patients with preexisting diabetes mellitus (2.2 for preterm premature rupture of membranes, 2.4 for preterm labor, and 9.5 for medically induced births), and those with antepartum bleeding (2.8 for preterm premature rupture of membranes, 3.6 for preterm labor, and 3.7 for medically induced births). Other sociodemographic, constitutional, life-style, and obstetrical characteristics differed across the groups. Variation in some of the risk factors among the preterm subtypes implies that epidemiologic assessment of the more specific outcomes would be advisable. (Epidemiology 1998;9:279–285)

The world trade center disaster and intrauterine growth restriction

Correction Contact me if this article is corrected. http://jama.ama-assn.org/cgi/content/full/jama;290/22/2943 Correction is appended to this PDF and also available at Citations Contact me when this article is cited. This article has been cited 25 times. Topic collections Contact me when new articles are published in these topic areas. Pregnancy and Breast Feeding; Occupational and Environmental Medicine Violence and Human Rights; Violence and Human Rights, Other; Womens Health;

Prenatal Pesticide and PCB Exposures and Birth Outcomes

Evidence is inconsistent or poorly understood for links between polychlorinated biphenyls (PCBs), 1,1′-dichloro-2,2′-bis(4-chlorophenyl)ethylene (DDE), and organophosphate (OP) pesticides and adverse pregnancy outcomes, although they are known developmental toxicants. We measured biomarkers of maternal exposure to DDE, PCB, and OP metabolites in the third trimester of pregnancy among 404 mothers in a multiethnic cohort in New York City. We also determined maternal paraoxonase (PON1), butyrylcholinesterase (BuChe), and PON1Q192R gene variant. Higher multivariate-adjusted DDE levels (but not PCB) were associated with lower birth weight (–98 g/log10 DDE, p = 0.096) and head circumference (–0.54 cm/log10 DDE, p = 0.030). DDE and PCB levels were not related to birth length, Ponderal index, or gestational age. Birth length was shorter for mothers with PON192RR slow genotype compared with PON192QQ (p = 0.026), and head circumference was inversely associated with maternal PON1 activity (p = 0.004). With slow-activity PON1 or PON192, urinary diethylphosphates (ΣDEPs) were associated with lower birth weight and dimethylphosphates (ΣDMPs) with shorter birth length. No associations were found between birth outcomes and BuChe. In summary, we found suggestive relationships between prenatal environmental biomarkers and birth outcomes in this population. Maternal susceptibility factors including PON1 and maternal weight contributed to the observed effects.

Maternal and neonatal risk factors for cryptorchidism.

We assessed risk factors for Cryptorchidism in a prospective hospital-based cohort study at Mount Sinai Hospital in New York City. We examined at birth 6,699 singleton male neonates who were delivered between October 1987 and October 1990. Follow-up examinations were undertaken at 3 months and 1 year for those diagnosed as cryptorchid at birth. We calculated prevalence ratios and adjusted odds ratios according to selected maternal and neonatal characteristics for those who remained cryptorchid at the 1-year assessment. We found elevated risks for maternal obesity [prevalence ratio = 2.42; 95% confidence interval (CI) = 1.11–5.27], for infants delivered by cesarean section (adjusted odds ratio = 2.17; 95% CI = 1.29–3.65), for low birthweight (adjusted odds ratio = 2.29; 95% CI = 1.12–4.70), for preterm birth (adjusted odds ratio = 2.25; 95% CI = 1.16–4.35), and for infants with congenital malformations (prevalence ratio = 13.97; 95% CI = 1.27–26.67). We observed a seasonal effect, with a peak in births of cryptorchid infants during September through November and a smaller peak during the months of March through May. We found no evidence that young women, white women, or primiparas were at increased risk.

Study design: Evaluating gene–environment interactions in the etiology of breast cancer – the WECARE study

IntroductionDeficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated.DesignTo examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses.ConclusionsOur study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions.

Corticotropin-releasing hormone and related pituitary-adrenal axis hormones in fetal and maternal blood during the second half of pregnancy.

There is little information available concerning the ontologic development of the human hypothalamic-pituitary-adrenal (HPA) axis nor of the potential interactions among fetal, maternal and placental-derived HPA axis hormones. This study evaluated levels of these hormones in matched maternal and fetal pairs during the second half of uncomplicated pregnancies. Immunoassays were used to measure serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol in 104 matched fetal and maternal blood samples. Fetal specimens were obtained by percutaneous umbilical blood sampling (PUBS) between 18 and 40 weeks in patients whose pregnancies resulted in healthy, term infants. Correlations among these hormones, and the effect of gestational age were assessed. Maternal CRH concentrations [median (range)] [1.10 ng/ml (0.15 to 23.69)] were significantly greater than fetal values [0.35 ng/ml (0.07 to 1.0)]. Levels of maternal CRH (r = 0.73; p < 0.001) but not fetal CRH (r = 0.01; p = 0.98) correlated with gestational age. Maternal ACTH decreased (r = -0.21; p = 0.04) while fetal ACTH increased (r = 0.35; p < 0.003) with gestational age. Both maternal (r = 0.45; p < 0.001) and fetal (r = 0.57; p < 0.001) cortisol levels increased with gestational age. Maternal serum CRH values correlated best with fetal cortisol (r = 0.40; p = 0.0002) and correlated modestly with maternal cortisol (r = 0.28; p = 0.01), fetal ACTH (r = 0.24; p = 0.03) and fetal CRH (r = 0.23; p = 0.04); but not with maternal ACTH (r = -0.12; p = 0.3). Maternal CRH concentrations increase in the third trimester and correlate with rising fetal cortisol levels.