Search

Objective 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. Methods Case–control sets of stored second-trimester serum-screening samples from 27 smoking and 90 nonsmoking pregnant women were developed. Smoking status was confirmed by measuring serum cotinine levels. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and DYS1 levels were determined using real-time polymerase chain reaction (PCR) to measure total and fetal cell-free DNA, respectively. At delivery, medical records were reviewed to confirm gender and determine other factors that could affect DNA values. Results Smoking was associated with significantly elevated GAPDH levels compared with nonsmokers (median: 97 662 genome equivalents (GE)/mL vs 38 217 GE/mL; p = 0.018). DYS1 levels were not statistically significantly elevated in smokers (p = 0.29). Other factors that affected DYS1 levels included maternal age in nonsmokers only (r2 = 0.30, p = 0.013) and maternal Synthroid use (p = 0.0045) Conclusion Pregnant smokers have threefold higher levels of total cell-free DNA compared with pregnant nonsmokers. Maternal age and Synthroid exposure may also affect circulating cell-free fetal DNA levels. Copyright © 2008 John Wiley & Sons, Ltd.

Objectives Integrated serum screening for Down syndrome is potentially more effective than current second-trimester screening. We report results of an intervention trial of integrated serum screening that involved 229 primary prenatal care practitioners throughout Maine. Methods Women provided a first-trimester serum (for PAPP-A) followed by a second-trimester serum (for AFP, uE3, hCG, and DIA). These five marker measurements were used to calculate a Down syndrome risk in the second trimester. Screen-positive women (risk ≥ 1:100) were managed according to standard practice. Results During 24 months' enrollment, 11 159 women provided a first-trimester sample (61% of women receiving screening services). Nine thousand seven hundred twenty-three women also provided a second-trimester sample; 8773 women satisfied gestational age criteria for testing in both trimesters. Integrated serum screening detected 14 of 16 Down syndrome cases (87%) and 79% after adjustment for trimester-of-ascertainment bias. The initial false-positive rate was 3.2% and was 2.7% when restricted to ultrasound-dated pregnancies. Performance was better than any combination of second-trimester markers. Implementation challenges included initial samples being collected too early and sample matching. Conclusions Integrated serum screening for Down syndrome was successfully implemented in primary care settings; screening performance was consistent with predictions. It provides an accessible and acceptable alternative to screening protocols that require nuchal translucency measurements. Copyright © 2005 John Wiley & Sons, Ltd.

Both a cross-sectional and a longitudinal study were performed to investigate whether or not the collection time should be taken into consideration when generating a patient's risk for fetal Down syndrome with multiple marker screening. Diurnal variations of third-trimester alpha-fetoprotein (AFP) levels and first-trimester human chorionic gonadotropin (hCG) levels have been previously reported. In addition, large episodic fluctuations of conjugated and unconjugated oestriol (uE3) as well as a diurnal variation have also been reported in the third trimester. If the levels of these analytes routinely fluctuate during the day, they could affect a patient's risk calculation for fetal Down syndrome. The longitudinal study evaluated ten non-diabetic women who underwent sequential sampling for AFP, hCG, and uE3. The cross-sectional study evaluated 1953 patients for these three markers whose time of sampling was recorded between 8·00 a.m. and 5·59 p.m. Using either study design, no significant effect was seen in the median MOM levels of the screening analytes as a function of the time of day.

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.

To examine the relationship between elevated antiphospholipid antibody levels in the maternal circulation and late fetal death, we carried out a case-control study in which levels of anticardiolipin and antiphosphatidylserine antibodies were measured in banked second-trimester sera from 309 pregnancies ending in fetal death and from 618 viable control pregnancies. The sera were obtained from a population base of approximately 22,000 pregnancies enrolled for maternal alpha-fetoprotein screening between 15 and 20 weeks' gestation. The anticardiolipin immunoglobulin G level was markedly elevated (15.6 SD) in one serum sample associated with a fetal death. Otherwise, the anticardiolipin and antiphosphatidylserine measurements were similar in the two populations. Several other factors known to be associated with fetal death were also examined, and these all demonstrated the expected relationship. Antiphospholipid antibody measurements obtained at 15 weeks' gestation or later in the general pregnancy population are not helpful in identifying pregnancies at risk for fetal death.

URATO, JULIETTE MADAN, ROBERT QUINN, ANDREA PULKKINEN, SABRINA D. CRAIGO, Tufts University New England Medical Center, Boston, Massachusetts, Foundation for Blood Research, Scarborough, Maine OBJECTIVE: It is well-established that maternal smoking during pregnancy is associated with several pregnancy complications, including preterm birth. Yet, while many women smoke during pregnancy, it is not known which of these will deliver prematurely. Inhibin A levels are known to be elevated in pregnant smokers compared with nonsmokers. Our objective was to determine if Inhibin A levels in pregnant smokers are associated with preterm delivery. STUDY DESIGN: A retrospective cohort study was performed. 7,795 pregnant smokers were identified in a database of 39,421 pregnant women who participated in a statewide serum screening program from 1999 to 2005. Pregnancy outcomes were obtained from the Maine birth records database that was cross-referenced to the serum screening database. Relative risks and 95% confidence intervals for preterm birth were estimated based on Inhibin A level. RESULTS: In the cohort of 7,795 smokers, there were 726 births 37 weeks (9.31%), 201 births 34 weeks (2.58%), and 76 births 30 weeks (0.97%). For pregnant smokers an elevated Inhibin A level was associated with preterm birth (see Table.) An Inhibin A level 2.0 MOM was found in 195 of the 726 pregnant smokers with a preterm birth 37 weeks (26.9%), 64 of the 201 34 weeks (31.8%), and 25 of the 76 30 weeks (32.9%). CONCLUSION: Pregnant smokers with an Inhibin A level 2.0 MOM are at increased risk of preterm birth. Those pregnant smokers with INH A levels 2.5 are at particularly high risk. A significant proportion of the smokers who will deliver prematurely will have an Inhibin A level 2.0 MOM.

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