Shirley J. Thompson

DECLINE IN PREVALENCE OF NEURAL TUBE DEFECTS IN A HIGH-RISK REGION OF THE UNITED STATES

Objectives. To conduct surveillance for neural tube defects (NTDs) in a high-risk region of the United States and to prevent occurrence and recurrence of NTDs through the periconceptional use of folic acid supplements. Design. Active and passive methods were used for surveillance of NTD-affected pregnancies and births during a 6-year period (October 1992–September 1998). Individual genetic counseling was used to prevent NTD recurrences and a public awareness campaign was used to reduce NTD occurrences. Setting. State of South Carolina. Patients. All cases of spina bifida, anencephaly, and encephalocele identified among 278 122 live births and fetal deaths to South Carolina residents during 1992–1998 were included. Main Outcome Measure. Changes in occurrence and recurrence rates during a 6-year period. Results. Over the 6 years of surveillance, the prevalence rates for NTDs decreased from 1.89 to .95 cases per 1000 live births and fetal deaths. The prevalence decrease is explained primarily by a decrease in cases of spina bifida. Isolated NTDs accounted for 297/360 (82%) NTDs and 63/360 (18%) had at least 1 other structural anomaly. Females predominated among isolated NTDs but the sex distribution was equal among NTD cases with other anomalies. Prevalence rates for whites (1.48 cases per 1000 live births and fetal deaths) were higher than rates for blacks (.87 cases per 1000 live births and fetal deaths). There were no NTD recurrences in 113 subsequent pregnancies to mothers of infants with isolated NTDs who took periconceptional folic acid. The rate of periconceptional folic acid use among women of childbearing years increased from 8% to 35% during the 6-year project period. Conclusion. The prevalence of NTDs in a high-risk region has declined coincident with the increased periconceptional use of folic acid supplements among women of childbearing age.neural tube defects, high-risk region, birth defects, folic acid, spina bifida, anencephaly, encephalocele.

Role of delayed feeding and of feeding increments in necrotizing enterocolitis

In spite of a number of studies on necrotizing enterocolitis, there remains controversy concerning prevention regimens, especially with regard to enteral alimentation. This report is of a matched case-control study of the relationship of necrotizing enterocolitis to timing of first feeding, size of feeding volumes and increments, and a risk factor index in 59 case patients with necrotizing enterocolitis and 59 matched control patients. Comparison with control patients showed that case patients were fed earlier, received full-strength formula sooner, and received larger feeding volumes and increments. More highly stressed infants, as measured by the risk index, were more vulnerable to larger feeding increments. Among case patients there was significant correlation of age at first feeding and age at diagnosis (p < 0.0001) even after control for birth weight and risk index score, indicating that delayed feeding was related to delayed onset of disease. These analyses support the theory that earlier, more rapid feeding places stressed infants at greater risk for the development of necrotizing enterocolitis, and that infants with more severe respiratory problems are more vulnerable to such feeding practices.

An epidemiologic study of smoking and primary infertility in women

OBJECTIVE To determine the relationship between cigarette smoking and primary female infertility. DESIGN Retrospective, case-control study. SETTING Population-based and randomly selected from eight geographic areas in the United States. PARTICIPANTS Women, 20 to 54 years of age, who were randomly selected to serve as the control group of the Cancer and Steroid Hormone Study were used for this study. Within this group, there were 483 women who were classified as having experienced primary infertility and 2,231 women eligible to serve as controls. Primary infertility, defined as 24 consecutive months of unprotected intercourse without conception, was documented from a calendar of each womens reproductive and contraceptive history. RESULTS Smoking one pack of cigarettes per day (odds ratio = 1.36) and starting to smoke before 18 years of age (odds ratio = 1.30) were significantly associated with increased risk of infertility. Life table and proportional hazards analysis indicated that smoking did not significantly increase the time required to conceive among infertile women. CONCLUSIONS Number of cigarettes smoked and age when the women began smoking contributed to infertility in this study. It is reasonable, therefore, to recommend that women stop smoking when they are attempting to become pregnant.

Association between Exercise and HIV Disease Progression in a Cohort of Homosexual Men

PURPOSE To study the relationship between exercise and human immunodeficiency virus (HIV) disease progression. METHODS 415 individuals (156 HIV positive, 259 HIV negative), from a cohort study of 851 homosexual men from New York City, 1985-1991. By 1991, 68 of the 156 persons developed Acquired Immune Deficiency Syndrome (AIDS) and 49 died with AIDS. Exercise was defined as self-report of exercising 3-4 times/week or daily at entry; less was considered nonexercise. CD4 lymphocyte decline was constructed for each subject by modeling log CD4 count against time in days. The association between exercise and progression to AIDS and death with AIDS, adjusting for baseline CD4 count, was determined using Cox model. Linear regression was used to model CD4 decline with exercise for HIV positive and HIV negative groups separately, adjusting for initial CD4 count. RESULTS Having exercised was associated with slower progression to AIDS at 1 year (HR = 0.68, 90% confidence interval (CI): 0.4-1.17); hazard ratios (HR) at 2, 3, and 4 years were 0.96, 1.18, and 1.36, respectively. Having exercised was also associated with slower progression to death with AIDS at 1 year (HR = 0.37, 90% CI: 0.14-0.94) with hazard ratios at 2, 3, and 4 years of 0.68, 0.98, and 1.27, respectively, suggesting a protective effect close to the time exercise was assessed, but an increased risk after 2 years. Exercising 3-4 times/week had a more protective effect than daily exercise. Exercisers in the HIV positive group showed an increase in CD4 count during a year by a factor of 1.07. CONCLUSION Moderate physical activity may slow HIV disease progression.

Maternal serum placental alkaline phosphatase level and risk for preterm delivery

OBJECTIVE The purpose of this study was to determine whether elevated midtrimester serum placental alkaline phosphatase levels are predictive of preterm delivery. STUDY DESIGN By use of banked serum specimens from a sample of women who had received maternal serum alpha-fetoprotein screening, placental alkaline phosphatase values for multiples of the median were obtained from 270 mothers who had experienced a preterm delivery and from 1598 mothers of term, appropriate-for-gestational-age infants. Specimens were analyzed for placental alkaline phosphatase by means of a monoclonal antibody enzyme-linked immunosorbent assay. Logistic regression was used to determine whether placental alkaline phosphatase was associated with preterm birth, while potential confounders were controlled for. RESULTS Women with placental alkaline phosphatase levels > or = 2.0 multiples of the median were significantly more likely to be delivered of a preterm infant in the current pregnancy compared with women with levels < 2.0 multiples of the median (odds ratio 2.9, 95% confidence interval 2.1 to 3.9). The likelihood of preterm birth increased significantly with higher multiples of the median (p < 0.001). CONCLUSION Women with elevated placental alkaline phosphatase levels are at increased risk for preterm delivery. Additional studies are needed to evaluate the clinical utility of placental alkaline phosphatase testing as a means of identifying mothers at risk for preterm birth.

Periconceptional multivitamin folic acid use, dietary folate, total folate and risk of neural tube defects in South Carolina

Abstract PURPOSE: To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies. METHODS: This population-based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 randomly selected controls. Women completed a food frequency questionnaire and were interviewed about lifestyle behaviors, pregnancy histories and use of multivitamins. RESULTS: Use of 0.4 mg or more of multivitamin folic acid at least 3 times per week during the periconceptional period showed no statistically significant reduction in NTD risk [adjusted odds ratio (AOR) = 0.55, 95% confidence interval (CI) = 025, 1.22]. After adjusting for covariates, protective effects for NTDs were observed at the highest quartiles of dietary folate and total folate (daily dietary folate plus daily multivitamin folic acid); the respective odds ratios were 0.40 (95% CI = 0.19, 0.84) and 0.35 (95% CI = 0.17, 0.72). CONCLUSIONS: This study illustrates some of the difficulties in determining effects of folic acid and dietary folate in a population where the consumption of foods rich in folate and the use of multivitamins are increasing and the rate of NTDs is declining. Studies are needed to monitor future changes in folate levels and their effect on health.

Intergenerational and environmental factors influencing pregnancy outcomes

PURPOSE: Factors that relate to the mothers own course of growth and development might influence later reproductive performances. This study examines the effect of maternal birth weight and maternal height and maternal weight gain, on term-small for gestational age (SGA) and preterm delivery.METHODS: Data used for this study were from the South Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) and birth certificate files for 1993-1995. Since PRAMS data were weighted to adjust for sampling probabilities, non-response and survey design, Survey Data Analysis (SUDAAN) software was used in all analyses.RESULTS: Maternal birth weight was strongly associated with term SGA (OR = 3.65; 95% CI = 1.83-7.29), but not preterm delivery among black mothers; it was associated with preterm delivery (OR = 1.86; 95% CI = 1.09-3.17), but not term-SGA for white mothers. Maternal birth weight was associated with term SGA among nonsmokers only (OR = 2.34; 95% CI = 1.33-4.11). Maternal weight gain modified the effect of height on birth outcomes. Among women with inadequate weight gain, there was a 3-fold increase in risk for term-SGA (OR = 3.06; 95% CI = 2.41-3.89) for short maternal height, but not for preterm delivery. Among women with adequate plus weight gain, the association between short maternal height and term-SGA was 2.7 (95% CI = 0.55-9.43) compared to 3.67 (95% CI = 0.1.41-9.56) between short maternal height and preterm delivery. Maternal weight gain also modified the effect of maternal height on both outcomes for black mothers and for nonsmokers only.CONCLUSIONS: Findings indicate the need for interventions directed to those women who can benefit most from appropriate targeted weight gain recommendations. Therefore, prevention methods should be implemented to encourage short stature women to gain adequate weight during pregnancy.

Primary infertility and oral contraceptive steroid use

OBJECTIVE To determine the association between combined monophasic oral contraceptive (OC) use and primary infertility. DESIGN Case-control. SETTING Women serving as controls of the Cancer and Steroid Hormone Study. PARTICIPANTS Women were 19 to 40 years of age at first conception or infertility diagnosis. Based on 24 consecutive months of unprotected intercourse without a recognized conception, 419 nulligravid women had primary infertility; controls were 2,120 fertile women. A calendar of each womens reproductive history was used to determine fertility status and contraceptive use before infertility diagnosis or first conception. MAIN OUTCOME MEASURE Primary infertility. RESULTS Combined monophasic OC use was associated with a lower frequency of primary infertility, particularly among younger (age 20 years) compared with older women (age 30 years) after adjusting for barrier method use and education. A similar association was found for duration of OC use. When adjusted for age at first conception or infertility and barrier method, both higher (> 50 micrograms) and lower (< or = 50 micrograms) estrogen dose use were associated with decreased risk of primary infertility. CONCLUSION Combined monophasic OC use was associated with a lower frequency of primary infertility.

Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospitals contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mothers Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.

Estimating environmental exposures to sulfur dioxide from multiple industrial sources for a case-control study.

This paper first discusses how population exposures to environmental pollutants are estimated from environmental monitoring data and the problems that are encountered in estimating risk from pollutants on the basis of ecologic studies. We then present a technique of estimating individualized exposures to an atmospheric pollutant, sulfur dioxide (SO2), through atmospheric transport modeling for a case–control study. The transport model uses the quantities of SO2 released from 30 geographically identified industrial facilities and meteorological data (wind speed and direction) to predict the downwind ground-level concentrations of SO2 at geographically identified residences, receptors, of 797 study subjects. A distribution of facility SO2 emissions, uncertainties in effective stack height, and model uncertainty are incorporated to examine the uncertainty in the predicted versus ambient monitoring SO2 levels, and to generate an exposure uncertainty distribution for both the cases and controls. The transport models accuracy is evaluated by comparing recorded ambient measurements of SO2 with the models predicted SO2 estimates at geographically identified ambient monitoring stations.