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OBJECTIVE: Insulin-like peptides (insulin, IGF-1, IGF-2) are essential regulators of foetal growth. We assessed the role of these peptides for birth size in a sex-specific manner. DESIGN: Cross-sectional cohort analysis. PATIENTS AND MEASUREMENTS: In 369 neonates, cord blood insulin, C-peptide, IGF-1 and IGF-2 levels were measured. Outcomes were placenta weight, birthweight, length and ponderal index. In linear regression models, the association of insulin-like peptides with growth outcomes was assessed, adjusted for gestational age and delivery mode. Interaction between insulin-like peptides and neonatal sex was assessed. RESULTS: No sex differences in levels of insulin-like peptides were observed. Significant interactions were found of sex with IGF-1 for birthweight, and of sex with C-peptide for all outcomes, except ponderal index. The association of IGF-1 (ng/mL) with birthweight was stronger and only significant in males (beta coefficient 3.30 g; 95%CI 1.98-4.63 in males and 1.45 g; -0.09-2.99 in females). Associations of C-peptide (ng/mL) with growth outcomes were stronger and only significant in females (placenta weight females: 181.3 g; 109.3-253.3; P < .001, males: 29.8 g; -51.5-111.1; P = .47, birthweight females: 598.5 g; 358.3-838.7: P < .001, males: 113.7 g; -154.0-381.4; P = .40). Associations of IGF2 with birthweight were similar in males and females. No associations were found with ponderal index. CONCLUSIONS: C-peptide and IGF-1 in cord blood associate with birthweight, length and placenta weight in a sex-specific manner, with stronger associations of C-peptide levels with placenta weight, birthweight and length in females and stronger associations of IGF-1 levels with birthweight in males.

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PURPOSE: To compare the obstetric and neonatal outcome in pregnancies complicated by gestational diabetes mellitus after amniocentesis for amniotic fluid insulin measurement or maternal blood glucose monitoring or both as selection criterion for therapy. MATERIAL AND METHODS: In a retrospective study, 408 diabetic pregnancies were analyzed; 307 were treated with diet alone (group 1) and 101 with diet and insulin (group 2). Pearson's chi2 or Fisher's exact test was used to assess obstetric and anthropometric data within these groups, and p values <0.05 were considered statistically significant. RESULTS: Group 1 - According to the method used, no significant differences were found for gestational age at birth (p = 0.396), mode of delivery (p = 0.79) and neonatal outcome parameters determined as mean birth weight (p = 0.348), birth weight above the 75th percentile (p = 0.473), mean ponderal index (PI; p = 0.434), pH of umbilical artery (p = 0.065) and of umbilical-vein blood (p = 0.052), mean Apgar scores at 1 (p = 0.56) and 5 min (p = 0.072), insulin (p = 0.25) and glucose (p = 0.535) in cord blood. Significant differences were found for birth weight above the 90th percentile (p = 0.005) and Apgar score <7 at 1 min (p = 0.019). Group 2 - Again, no significant differences were observed in terms of gestational age at birth (p = 0.219), mode of delivery (p = 0.386), mean birth weight (p = 0.59), birth weight above the 75th (p = 0.701) and 90th percentiles (p = 0.487), mean PI (p = 0.156), pH of umbilical-artery (p = 0.197) and umbilical vein blood (p = 0.056), Apgar scores at 1 (p = 0.58) and 5 min (p = 0.52), insulin (p = 0.67) and glucose (p = 0.11) in cord blood. CONCLUSION: In retrospective analysis there was no significant difference in outcome parameters in pregnancies complicated by gestational diabetes dependent on the method used as selection criterion for therapy.

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OBJECTIVES: The aim of the study was the detection, quantification and correlation of cell-free fetal (cff) DNA in maternal urine and plasma in normal and complicated pregnancies during the third trimester. METHODS: One hundred and fifty-one urine and plasma samples obtained from 96 women carrying male fetuses, and 55 carrying female fetuses were collected and analyzed for cff-DNA using fluorescent PCR and quantitative real-time PCR. DNA was extracted from 1 mL maternal urine and analyzed with two different primer sets (SRY and DYS-14). The concentrations of cff and total DNA in maternal plasma were correlated with maternal and obstetric parameters using appropriate correlation analyses. RESULTS: Y-chromosome-specific sequences were detected in 31 of 96 (32.3%) urine samples collected from women pregnant with male fetuses using DYS-14 and in 6 of 96 (6.3%) urine samples using SRY as primers using real-time PCR. All 96 plasma samples obtained from women carrying male fetuses were positive for cff-DNA using real-time PCR. Cff-DNA exhibited a correlation with gestational age (R = 0.244; P = 0.018) and an inverse correlation with the latency between blood collection and birth (R = - 0.218; P = 0.036). Total DNA showed a correlation with placental weight (R = 0.182; P = 0.034) and pregnancy-associated complications (R = 0.280; P < 0.001). CONCLUSION: Our data confirm that cff-DNA is cleared by the kidneys in detectable amounts, but due to its low concentration or problematic detection in maternal urine this source seems inappropriate for noninvasive prenatal diagnosis.

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The uterine cervix has to provide mechanical resistance to ensure a normal development of the fetus. This is guaranteed by the composition of its extracellular matrix, which functions as a fiber-reinforced composite. At term a complex remodeling process allows the cervical canal to open for birth. This remodeling is achieved by changes in the quality and quantity of collagen fibers and ground substance and their interplay, which influences the biomechanical behavior of the cervix but also contributes to pathologic conditions such as cervical incompetence (CI). We start by reviewing the anatomy and histological composition of the human cervix, and discuss its physiologic function and pathologic condition in pregnancy including biomechanical aspects. Established diagnostic methods on the cervix (palpation, endovaginal ultrasound) used in clinics as well as methods for assessment of cervical consistency (light-induced fluorescence, electrical current, and impedance) are discussed. We show the first clinical application of an aspiration device, which allows in vivo testing of the biomechanical properties of the cervix with the aim to establish the physiological biomechanical changes throughout gestation and to detect pregnant women at risk for CI. In a pilot study on nonpregnant cervices before and after hysterectomy we found no considerable difference in the biomechanical response between in vivo and ex vivo. An outlook on further clinical applications during pregnancy is presented.

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OBJECTIVES: To evaluate whether cell-free fetal (cff) DNA in maternal plasma during the second trimester is a marker for developing pregnancy-associated complications. Two PCR techniques for the detection and quantitation of fetal DNA were compared. METHODS: Plasma samples were prospectively collected from 84 pregnant women carrying male fetuses before amniocentesis (14-29 weeks). We later recorded 26 pregnancies with complicated outcomes, including five cases of fetal chromosomal abnormalities. For statistical analysis, two overlapping subgroups A and B were made. Each group was separately compared for total and fetal DNA with a corresponding group considered normal using Wilcoxon rank sum test. Male fetal DNA concentration in maternal plasma was quantified using real-time quantitative polymerase chain reaction (PCR) of SRY sequences. The samples were also analyzed by quantitative fluorescent PCR (QF-PCR) using highly polymorphic short tandem repeat DNA sequences (STRs), and the percentage of relative fetal allele concentration in maternal alleles was calculated and compared to the fetal/total DNA ratio obtained by real-time PCR. RESULTS: Quantities of total and fetal circulating DNA were significantly correlated (r(2) = 0.44, P < 0.0001) with a median total DNA concentration of 522 GE/mL (range 51-3047) and a median fetal DNA concentration of 8 GE/mL (range 0-879). Neither level was correlated with gestational age in pregnancies with normal (r(2) = -0.05; P = 0.66, and r(2) = 0.02; P = 0.88, respectively) and abnormal (r(2) = 0.45; P = 0.17, and r(2) = 0.11; P = 0.76, respectively) outcomes. Although both total and fetal DNA levels were always higher in women carrying pregnancies with chromosomal aberrations or having other pregnancy complications (P-values range from 0.028 to 0.267), these differences reached statistical significance only for total DNA levels between the group A and corresponding normal pregnancies (P = 0.028). The correlation between the fetal/total DNA ratio obtained by real-time PCR and the percentage of relative fetal allele concentration in maternal alleles obtained by QF-PCR was not found to be statistically significant (r(2) = 0.04; P = 0.76). CONCLUSION: Our results confirm the clinical value of fetal DNA measurement in maternal plasma during the second trimester as a supplement for the diagnosis of aneuploidies. Its use as a screening instrument for complications that develop later in pregnancy seems to be limited but needs further investigation. Although the QF-PCR assay has the advantage of being applicable to both female and male fetuses, this approach cannot be used for quantitation of cff DNA in maternal plasma samples.

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