Andrea Pulkkinen

Association between Exposure to Environmental Tobacco Smoke and Exacerbations of Asthma in Children

BACKGROUND Exposure to environmental tobacco smoke, as reported by parents, has been linked to diminished pulmonary function and more frequent exacerbations of asthma in children with the disease. Further insight into this association might be gained by using urine cotinine levels to measure actual exposure. METHODS We measured urine cotinine levels in 199 children with asthma; 145 also underwent pulmonary-function studies. A parent answered questions about each childs exposure to environmental tobacco smoke. Acute exacerbations of asthma during the preceding year were documented through blinded review of medical records. Possible confounding factors were accounted for by the use of multivariate analysis and by comparisons of serum theophylline levels in exposed and unexposed children. RESULTS The median urine cotinine levels were 5.6 ng per milliliter in the 116 children reported not to have been exposed to tobacco smoke, 13.1 ng per milliliter in the 53 children exposed to cigarette smoking by the mother or other persons, and 55.8 ng per milliliter in the 30 children exposed to cigarette smoking by the mother and other persons. Acute exacerbations of asthma increased with exposure, whether such exposure was reported by a parent or identified on the basis of the cotinine level; the relative risks for the highest as compared with the lowest exposure category were 1.8 (95 percent confidence interval, 1.4 to 2.2) for reported exposure and 1.7 (95 percent confidence interval, 1.4 to 2.1) for exposure indicated by cotinine levels. The forced expiratory volume in one second (FEV1), the forced expiratory flow between 25 and 75 percent of vital capacity, and the ratio of FEV1 to forced vital capacity also decreased with increases in both measures of exposure. CONCLUSIONS Measurement of urine cotinine levels provides further evidence of an association between exposure to environmental tobacco smoke and pulmonary morbidity in children with asthma. These data emphasize the need for systematic, persistent efforts to stop the exposure of children with asthma to environmental tobacco smoke.

Prenatal Screening for Down's Syndrome with Use of Maternal Serum Markers

Abstract Background. Approximately 35 percent of all cases of Downs syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case–control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Downs syndrome. Methods. We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Downs syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Downs syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestationa...

The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy:

Objective: To further explore first and second trimester reference ranges for thyroid stimulating hormone (TSH) and examine within-person variability of TSH and thyroid peroxidase (TPO) antibody. Setting: Women coming for routine prenatal care in early pregnancy agreed to participate in a trial of integrated serum screening for Downs syndrome. Two serum samples were obtained from each woman, one each in the first and second trimesters. These samples were also available for TSH and TPO measurements in the present study. Methods: TSH and TPO antibody measurements were performed in 1126 women with ultrasound-dated pregnancies who provided serum samples in both trimesters. TSH reference ranges were established for the entire cohort and for the antibody-negative subgroup. Within-person variability of TSH measurements between trimesters was examined. Results: Median TSH values are lower in the first trimester than in the second (1.00 versus 1.29 mIU/l), but 98th centile values are higher (5.20 versus 4.18 mIU/l). High correlation exists between individual womens first and second trimester TSH measurements (r=0.75, r2=0.56, p<0.001). Among 23 women with TSH values above the 98th centile in the second trimester, 17 (74%) were over the 95th centile in the first trimester. TPO antibody measurements are also highly correlated between trimesters (r=0.97, r2=0.94). Conclusion: Proper interpretation of TSH measurements during pregnancy requires that laboratories establish and monitor appropriate reference ranges. TSH levels show high within-person consistency between trimesters.

Mid-Gestational Maternal Free Thyroxine Concentration and Offspring Neurocognitive Development at Age Two Years

CONTEXT Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy. OBJECTIVE The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy. DESIGN This was an observational, nested case-control study. SETTING The study was conducted at physician offices and prenatal clinics throughout Maine. STUDY SUBJECTS Between May 2004 and March 2006, TSH was measured in 5734 women in conjunction with second-trimester Down syndrome screening. After completion of pregnancy, free T(4) was measured in stored second-trimester sera from euthyroid women (TSH 0.1-3.5 mIU/ml; n = 5560). Women with free T(4) at the third centile or less (n = 99) were matched with women whose free T(4) was at the 10th to the 90th centile (n = 99). INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURE Bayley Scales of Infant Development (BSID III) were administered to the 198 offspring at age 2 yr. Scores for cognitive, language, and motor development were compared between matched pairs of offspring from the two groups before and after correcting for relevant variables. RESULTS Unadjusted BSID-III scores (cognitive, language, and motor) were lower by about 3% at age 2 yr among offspring of 98 hypothyroxinemic women (cases), reaching borderline significance for cognitive and motor scores. After adjustment for gestational age, the childs age at testing, maternal weight, and education, all differences diminished and became nonsignificant. Scores less than 85 were more frequent among case children but did not reach statistical significance (P = 0.14). CONCLUSIONS Isolated hypothyroxinemia during the second trimester is not associated with significantly lower BSID-III scores at age 2 yr, compared with scores for offspring of matched euthyroxinemic women.

Simultaneous fetal and maternal cotinine levels in pregnant women smokers

OBJECTIVE Our purpose was to determine the simultaneous concentrations of serum cotinine in both fetal and maternal blood. STUDY DESIGN Serum cotinine levels were measured in 11 maternal-fetal pairs at percutaneous umbilical blood sampling. Statistical analysis was performed by means of a one-group t test to determine whether the ratio of fetal-to-maternal cotinine was significantly different from 1. RESULTS Fetal cotinine levels ranged from 75% to 110% of maternal values (mean ratio 0.90, 95% confidence interval 0.83 to 0.97). Fetal levels were significantly lower than maternal concentrations (p = 0.02). CONCLUSIONS Cotinine, a metabolite of nicotine used to quantify exposure to tobacco smoke, readily gains access to the fetal circulation. Fetal cotinine concentrations in pregnant women smokers are, on average, 90% of maternal values throughout gestation.

Smoking in pregnancy is associated with increased total maternal serum cell‐free DNA levels

Cell‐free DNA is a marker of cellular apoptosis and necrosis. We wished to determine if maternal smoking affects maternal and fetal serum cell‐free DNA levels.

The relationship between serum β1-glycoprotein and α-fetoprotein levels in the second trimester and birth weight

Pregnancy-specific /3 1-glycoprotein (SP1) is produced by the placenta and released into the maternal circulation in steadily increasing amounts, with peak concentrations occurring at the thirty-eighth gestational week. Low SP1 levels have been found in association with intrauterine growth disorders in the third trimester, but this association has been less clear in the second trimester.1 Second-trimester SP, observations have been sparse. We carried out the present study to evaluate further whether a relationship might exist between second-trimester SP1 levels and birth weight and to compare SP1 with a-fetoprotein (AFP), the association of which with birth weight is already well defined. We selected 84 frozen, banked second-trimester serum specimens associated with viable singleton infants s2,500 gm. We then selected an equal number of similarly stored serum samples associated with infants ~3,500 gm, matched for maternal weight and gestational age. Fetal sex distributions were the same in both groups. The population from which samples were obtained was white. SP1 and AFP measurements were performed on these samples by means of radioimmunoassays developed in our laboratory. Median SP1 and AFP values are presented for lowbirth weight and normal-birth weight groups in Table l. While significant differences exist between the groups for both proteins measured, AFP is the more striking of the two. The two graphs in Fig. I contain

Prenatal Screening for Downʼs Syndrome With Use of Maternal Serum Markers

BACKGROUND Approximately 35 percent of all cases of Downs syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Downs syndrome. METHODS We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Downs syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Downs syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Downs syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Downs syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Downs syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Downs syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Downs syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.