Gestational Age-specific Reference Intervals Research Articles

Gestational age-specific reference intervals for androgens in pregnancy.

Androgen could impact cervical remodelling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval (RI) of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism. We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models. A4 and TT levels increased across the gestation, and they closely correlated with each other (R = 0.90, P=<0.001), whereas 17-OHP level decreased from 5th gestational week to 16th gestational week and then increased afterward towards the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with p ≤0.01, whereas mothers carrying male versus female fetuses have comparable levels of A4, TT, and 17-OHP. The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE.

Steroid profile in dried blood spots by liquid chromatography tandem mass spectrometry: Application to newborn screening for congenital adrenal hyperplasia in China

BackgroundNewborn screening for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone dissociation-enhanced, lanthanide fluorescence immunoassay (DELFIA) generates a large number of false-positive results. The present study aimed to improve the sensitivity of the CAH neonatal screening by including second-tier steroid profiling in dried blood spots (DBS) using liquid chromatography tandem mass spectrometry (LC-MS/MS). MethodsWe developed and validated a LC-MS/MS method for simultaneous determination of six steroids in DBS, including androstenedione, testosterone, 17-hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, and cortisol. Two 5-mm blood spots were eluted by internal standard working solution. We analyzed 1170 DBS samples from neonates to determine gestational age-specific reference intervals. In order to test the specificity of the second-tier method, we analyzed 707 cards with a positive screening by DELFIA. ResultsValues of intra- and inter-day precision coefficients of variance and accuracy were 2.0%–13.3% and 85.8%–114.5%, respectively. Recovery ranged from 85.0% to 106.9%. The lower limit of quantification was 0.5 ng/mL for 21-deoxycortisol, 0.25 ng/mL for 17-hydroxyprogesterone and cortisol, and 0.1 ng/mL for testosterone, androstenedione, and 11-deoxycortisol. In addition, the linearity range was 0.25–50 ng/mL (R2 > 0.99). According to the 17-hydroxyprogesterone levels and ratios of (androstenedione + 17-hydroxyprogesterone)/cortisol in the 707 positive screening samples, 77 neonates should receive recall visit. The number of false-positive results reduced by 89.1%. Totally, 18 newborns were diagnosed with 21-hydroxylase deficiency, one with P450 oxidoreductase deficiency and one with 11β-hydroxylase deficiency. With two-tier screening, the positive predictive value increased to 26.0%. ConclusionsThe second-tier steroid profiling by LC-MS/MS reduced the false-positive rate and improved the positive predictive value of CAH screening. We suggest applying this steroid profiling assay as a second-tier test for CAH screening in China.

Improving diagnostic accuracy in pregnancy with individualised, gestational age-specific reference intervals

Background and aimsInvestigations in pregnancy should be interpreted using pregnancy-specific reference intervals (RIs). However, because of the progressive nature of pregnancy, even pregnancy-specific RIs may not be equally representative at different gestations. We proposed that gestational age-specific RIs may increase diagnostic accuracy over those with fixed limits. Materials and methodsThe trajectory of platelets was mapped in 32,778 pregnant women, using 116,798 results. Then we evaluated the accuracy with which a low measurement in early pregnancy (<3rd centile) predicted thrombocytopaenia at term, compared to the existing limit (<150 × 109/L). ResultsPlatelets fell by 14.8% between 8 and 40 weeks. Platelets below the 3rd centile before 20 weeks predicted thrombocytopaenia at term (<100 × 109/L) with a significantly greater degree of accuracy than a fixed limit (AUC 0.86 vs. 0.76, p = 0.004). ConclusionPregnancy-specific RIs can be defined using routinely collected hospital data, and the abundance of such freely available data enables a detailed investigation of temporal changes throughout gestation. Individualised RIs offer improved accuracy profiles, over and above those already derived specifically from pregnant populations. Clinicians should consider how this may be used to improve diagnostic accuracy for biomarkers used in current clinical practice, and those yet to be defined.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393 μIU/ml, 1.01-1.54 ng/dl, and 2.51-3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

Serum TBA and GCA Levels Across Pregnancy and the Gestational Age-Specific Reference Intervals for Pregnant Chinese.

Reference intervals of clinical laboratory indexes are the basis of interpretation of test results. While intrahepatic cholestasis of pregnancy (ICP) could severely threaten maternal and fetal health, reference intervals of the biomarkers serum total bile acids (TBA) and glycocholic acid (GCA) are unsatisfactory. The purpose of this study was to derive gestational age-specific reference intervals for serum TBA and GCA in a Chinese population to promote early diagnosis of ICP. A total of 416 healthy pregnant Chinese were recruited and divided into three groups by gestational age: 140 in the first trimester (1 - 13 weeks) group, 136 in the second trimester (14 - 27 weeks) group, and 140 in the third trimester (≥ 28 weeks) group. Serum TBA and GCA levels were measured respectively by cyclic enzymatic method and latex enhanced immune turbidimetry. Reference intervals were calculated with non-parametric method. The reference intervals of serum TBA are 0.90 - 6.60 μmol/L, 1.20 - 9.10 μmol/L, and 1.50 - 8.90 μmol/L respectively in the first, second, and third trimester. The reference intervals of serum GCA are 0.24 - 1.14 μg/mL in the first and second trimesters (combined) and 0.00 - 2.04 μg/mL in the third trimester. Gestational age-specific reference intervals of serum TBA and GCA for pregnant Chinese were derived in strict accordance with CLSI C28-A3 guidelines, which will be valuable for early diagnosis of ICP.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R=0.10; P=.051), or UCR and Q-UCR (R=0.09; P=.11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Development of Gestational Age-Specific Thyroid Function Test Reference Intervals in Four Analytic Platforms Through Multilevel Modeling.

Background: A population-based reference interval (RI) of thyroid hormones in pregnancy using a standardized methodology is crucial for clinicians to make accurate diagnoses and important for the comparison of test results obtained from different analytic platforms. Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation, after exclusion of subjects with antibodies to thyroid peroxidase, thyroglobulin or thyrotropin receptor. Gestational age-specific RIs were constructed by using polynomial regression equations with MLwiN. Results: Free thyroxine (fT4) levels rose to a peak at the 7th-8th gestational weeks and then declined gradually till 28th week, while thyrotropin (TSH) level decreased from early pregnancy to a nadir at the 9th week. The data support the recent notion by the American Thyroid Association to raise the TSH upper RI to 4.0 mIU/L. We also demonstrate that thyroid hormone reference ranges are not affected in a mildly iodine-deficient population and by including women with the presence of antibodies against thyroid peroxidase and thyroglobulin who are otherwise healthy. Conclusions: The study highlights a methodology in constructing gestational age-specific thyroid function test RIs on different analytic platforms to provide a better interpretation and comparison of results obtained across different platforms.

Establishing population and gestational age specific TSH reference intervals for common methods in Australia using the transference technique

Establishing population and gestational age specific TSH reference intervals for common methods in Australia using the transference technique

Establishing population and gestational age specific tft reference intervals for the roche method using local data by data mining

Establishing population and gestational age specific tft reference intervals for the roche method using local data by data mining

Establishing population and gestational age specific TFT reference intervals for the Abbott method using local data mining

Establishing population and gestational age specific TFT reference intervals for the Abbott method using local data mining

Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China.

Aims Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish the essential reference intervals for a range of analytes during pregnancy. Methods A cross-sectional study was performed in 13,656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analysed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method. Results Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, β2-microglobulin and cystatin-C fell significantly during the first trimester and then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established. Conclusions The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.

Gestational age-specific reference intervals for serum thyroid hormone levels in a multi-ethnic population.

Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups. A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles). Reference intervals for serum thyroid hormones at 9-14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01-2.39 mIU/L; free T4, 11.4-19.5 pmol/L; free T3, 4.23-6.69 pmol/L; total T4, 77.8-182.4 nmol/L; total T3, 1.39-2.97 nmol/L. No differences in the five thyroid parameters' reference intervals are detectable among the ethnic groups except that at study visit 3 (28-32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99-3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70-2.98 nmol/L). The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

Evaluation of lead and essential elements in whole blood during pregnancy: a cross-sectional study.

Physiological concentrations of some elements fluctuate during pregnancy due to the increased requirements of growing fetus and changes in the maternal physiology. The aim of the study is to evaluate the distribution at different stages of pregnancy in healthy Chinese women and to show the association between trace elements and gestational age-specific reference intervals. A cross-sectional study was performed in 1089 pregnant women and 677 nonpregnant control women. Five element concentrations, including Cu, Zn, Ca, Mg, Pb in the blood were determined by atomic absorption spectrometry. Spearman's rank correlation test was used to assess the relationship between weeks of gestation and blood element concentrations. The mean levels of Cu and Mg were 23.64±4.69μmol/L and 1.36±0.12mmol/L, respectively, in the control women. While 0.68% of all pregnant women showed Cu levels below the normal ranges, the levels of Mg were comparable in different groups. Though the overall mean blood zinc and Ca concentrations (83.84±17.50μmol/L and 1.60±0.15mmol/L, respectively) increased gradually with the progress of gestation, the Zn and Ca deficiency levels (16.6 and 3.6%, respectively) decreased with the advance of gestation. Compared with nonpregnant group, the concentrations of Cu, Zn, Ca, Mg, Pb during the different stages of pregnancy, as a whole, were significantly different. Positive correlations were observed between weeks of gestation and blood Cu, Ca, Pb concentrations (r=0.301, 0.221, 0.223; P<0.05). There was a negative correlation blood Mg concentrations and weeks of gestation (r=-0.321; P<0.05). A weak positive correlation was noted between Zn concentrations and weeks of gestation (r=0.125; P<0.05). The importance of Cu and Mg deficiency and supplementation is well realized, but, Zn/Ca deficiency and Pb exposure is still exist; the overall deficiency of pregnant women was not so optimistic. During pregnancy, the established reference values will provide an important guidance for the reasonable supplementation of essential elements and surveillance of lead overexposure.

Cancer antigen 125 after delivery in women with a normal pregnancy: a prospective cohort study.

To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery, and early postpartum period. Prospective observational study. Department of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte, Denmark. Eight hundred and one women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies. Samples were collected at gestational weeks 13-20, 21-28, 29-34, 35-42, during labor, and on first and second day postpartum. Reference intervals were calculated for each gestational period as recommended by the International Federation of Clinical Chemistry and Laboratory Medicine. Concentration of serum CA-125 during the gestational period and around delivery. CA-125 was fairly stable below 35 U/mL during pregnancy but increased markedly during vaginal delivery, to a minor degree during emergency cesarean section, and only slightly during elective cesarean section. In the early postpartum period, CA-125 decreased with an apparent half-life of 24 h. The CA-125 cut-off value (<35 U/mL) used for non-pregnant women can be used for women during pregnancy after gestational week 13 as a supplement to ultrasound evaluation of ovarian cysts. The wide range of CA-125 concentration during normal pregnancies makes it unlikely that small fluctuations in CA-125 can be clinically useful for identifying other conditions. Measuring CA-125 around the time of delivery is not recommended. Gestational age-specific reference intervals during normal pregnancy are not needed.

Prevalance and fetomaternal outcome of thyroid disorder in pregnanacy

Background: Thyroid diseases are the commonest endocrine disorders affecting women of reproductive age group and hence constitute the commonest endocrine disorder in pregnancy also. It has long been recognized that maternal thyroid hormone excess or deficiency can influence the outcome for mother and fetus at all stages of pregnancy as well as interfere with ovulation and fertility. Thyroid dysfunction is often overlooked in pregnant women because of the nonspecific symptoms and the hyper metabolic state of pregnancy. Hence thyroid function test becomes essential to know the thyroid status in pregnancy and also to detect the subclinical disease. Aims & Objective: To establish the prevalence and effect of thyroid disorder on pregnancy outcome. Materials and Methods: The study is an observational study carried on 100 women coming for antenatal check-up in Private hospital, Ahmedabad from January 2011 to January 2012. All women who were included in this study were followed from 11-14 weeks of pregnancy up to delivery. Results: It was observed that the maximum numbers of patients were in 21– 25 years (52%) age group. Euthyroid (87%), hyperthyroid (1%), subclinical hyperthyroid (2%), hypothyroid (2%), and subclinical hypothyroid (8%) cases were detected. Neonatal jaundice developed in all Hyperthyroid patient, 50% (1/2) of patients with Subclinical hyperthyroidism, 50% (1/2) of patients with Hypothyroidism, 75% (6/8) of patients with Subclinical Hypothyroidism and 48.27% (42/87) of patients with Euthyroid. Conclusion: Gestational age specific reference intervals are of utmost importance by which clinicians can reliably evaluate thyroid function and monitor thyroxine replacement therapy in pregnant women. TPOAb (Thyroid peroxidase Antibody) positive patients are associated with an increased risk of abortion and these infants are more often born preterm. TSH is the hallmark in detection of hypothyroid as well hyperthyroid so TSH should be included in the list of routine investigations done in all antenatal women in first trimester. If TSH values are abnormal then FT3, FT4 and TPOAb need to be checked.

Thyroid function and thyroid autoimmunity in apparently healthy pregnant and non-pregnant Mexican women.

Thyroid disorders are common in women of reproductive age, and thyroid dysfunction during pregnancy has been associated with adverse outcomes for mother and child. Thyroid function and thyroid function tests (TFTs) can be influenced by a variety of factors, such as ethnicity, the presence of autoimmune thyroid disease (AITD), dietary iodine intake, pregnancy, and methodological differences. However, no large-scale studies have been published which examine TFTs and prevalence of AITD in Mexican pregnant women and women of reproductive age. TFTs and thyroid autoantibody testing were performed on 660 pregnant and 104 non-pregnant women from Mérida, Yucatán, Mexico. After removal of thyroid autoantibody positive individuals and women with thyroid stimulating hormone (TSH) >4.94 mIU/L, reference intervals were calculated for TFT for non-pregnant women and pregnant women by trimester. Anti-thyroidperoxidase antibodies (TPO-Ab) and/or anti-thyroglobulin antibodies (Tg-Ab) were positive in 14.4% and 13.5% of non-pregnant and pregnant women, respectively. TSH values were significantly higher in women who were positive for TPO-Ab and co-positive for TPO-Ab and Tg-Ab. TSH values were also significantly higher in Tg-Ab positive pregnant women. Other TFTs were not significantly different based on antibody status. Using antibody negative women, reference intervals were determined for TFTs in pregnant (gestational age-specific) and non-pregnant women. Laboratory evidence of AITD is common in this population of Mexican pregnant and non-pregnant women. TFT results and reference intervals are influenced by pregnancy and thyroid autoimmunity. For optimal interpretation of TFT results, gestational age-specific reference intervals established using a local patient population should be used.

Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean women

Maternal thyroid dysfunction during pregnancy has been associated with adverse outcomes for both the mother and child. For this reason, it is important to understand thyroid status in pregnant women. However, there are relatively few published studies that examine thyroid function tests (TFT) and thyroid autoimmunity in non-Western pregnant women. Serum samples were longitudinally collected throughout pregnancy from 108 Korean women. TFT, thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) testing was performed. The impact of gestational age on TPO-Ab and Tg-Ab levels was evaluated and gestational age-specific reference intervals for TFT were established in antibody negative women. In the first trimester, TPO-Ab and Tg-Ab were positive in 13.9% and 16.7% of women, respectively. For antibody positive women, median autoantibody levels for TPO-Ab and Tg-Ab dropped from first trimester to near term (133.7-10.5 IU/mL, and 162.1-21.9 IU/mL, respectively). Antibody status influenced thyroid stimulating hormone (TSH) during the first trimester, and TSH, free T4 (FT4) and total T4 (TT4) in the early second trimester. Later in gestation, no significant differences in TFT were found based on antibody status. Gestational age-specific reference intervals for TFT were calculated in antibody negative women. Laboratory evidence of autoimmune thyroid disease (AITD) is common in this population of pregnant Korean women. Antibody status influences TFT values in the first and early second trimester. Thyroid autoantibody status and titer change in an individual-specific manner throughout pregnancy. Gestational age-specific reference intervals should be utilized for interpretation of TFT results in pregnant women.

Reference intervals of D-dimer during the pregnancy and puerperium period on the STA-R evolution coagulation analyzer

BackgroundPregnant women are at a hyper-coagulable state with a higher risk of deep venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC), which could be life threatening. We established gestational age-specific reference intervals for D-dimer, and estimate the role of D-dimer test in ruling out VTE and DIC in pregnant women. MethodsWe followed 1343 healthy pregnant women and 1042 uncomplicated postpartum women to establish gestational age-specific reference intervals of D-dimer during normal pregnancy. Eighty uncomplicated non-pregnant women were chosen as control group. D-dimer testing was also performed among the patients with pregnancy-related complications. ResultsD-dimer concentration increased progressively during the pregnancy and peaked at the first postpartum day, and then it began to decrease steadily and reach to non-pregnant concentrations on the 42nd postpartum day. The results of several cases that had clinical suspicion of VTE were compared with those of the reference group. ConclusionsThe study provides reference intervals of D-dimer during the pregnancy and postpartum period for women of Chinese Han ethnicity using latex-based immunoturbidimetry on the STA-R evolution coagulation analyzer. Further studies are needed to validate these reference ranges and assess the clinical utility of the reference intervals for D-dimer.

Gestational age-specific reference intervals for blood copper, zinc, calcium, magnesium, iron, lead, and cadmium during normal pregnancy

ObjectivesThe aim of this study was to investigate the blood copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe), lead (Pb), and cadmium (Cd) concentrations in women of ≤12 (group I), 13–20 (group II), 21–27 (group III), 28–35 (group IV), and 36–42 (group V) weeks of gestation and compare them with those in nonpregnant women. Design and methodsThe cross-sectional study was performed in 2380 pregnant women [group I (n=550); group II (n=552); group III (n=600); group IV (n=553); and group V (n=125)] and 552 nonpregnant women as controls. Blood seven element concentrations, including Cu, Zn, Ca, Mg, Fe, Pd, and Cd, were determined by atomic absorption spectrometry (AAS). ResultsCompared with the nonpregnant women group, the concentrations of Cu, Zn, Ca, Mg, Fe, Pb, and Cd at ≤12, 13–20, 21–27, 28–35, and 36–42weeks of gestation, on the whole, were significantly different. Blood Cu, Mg, Ca, Fe, Pb, and Cd concentrations were correlated with weeks of gestation (P<0.05). The gestational age-specific reference intervals were established for Cu, Zn, Ca, Mg, Fe, Pd, and Cd. ConclusionsThe established reference intervals for Cu, Zn, Ca, Mg, and Fe can provide important guidance for the reasonable supplementation of essential elements in pregnancy. And the reference intervals for Pd and Cd can play an important part in the surveillance and diagnosis of environmental overexposure.

Challenges in the evaluation of D-dimer and fibrinogen levels in pregnant women

IntroductionNormal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. The aim of the study was to follow the changes of haemostatic parameters and to establish gestational age-specific reference intervals during normal pregnancy. Materials and methodsBlood samples of 83 pregnant women were collected at gestational weeks 16, 26 and 36. Fibrinogen, D-dimer, and C-Reactive Protein (CRP) were examined. Reference intervals were calculated for fibrinogen, D-dimer tests with two different methods (mean±2 SD or median and 2.5th and 97.5th percentiles with 90% confidence intervals). Resultsfibrinogen and D-dimer increased progressively throughout pregnancy. Mean fibrinogen levels were higher than the maximum of the conventional reference interval, already in the 16th week of pregnancy. D-dimer levels were at or above the conventional cutoff point (250ng/mL) throughout the pregnancy in 42% of pregnant women, while in the 36th week 98% of them displayed elevated D-dimer levels. CRP did not increase in normal pregnancy. ConclusionsThere seems to be an emerging need to reconsider fibrinogen and D-dimer values from a different aspect in pregnancy compared to non-pregnant reference intervals. New reference ranges are suggested to be established in pregnancy.