The Role of Growth Trajectories in Classifying Fetal Growth Restriction

OBJECTIVE: To examine the validity of a growth trajectory method to discriminate between pathologically and constitutionally undergrown fetuses using repeated measures of estimated fetal weight.

METHODS: In a prospective, observational, multicenter study in Ireland, 1,116 women with a growth-restricted fetus diagnosed participated with the objective of evaluating ultrasound findings as predictors of pediatric morbidity and mortality. Fetal growth trajectories were based on estimated fetal weight.

RESULTS: Between 22 weeks of gestation and term, two fetal growth trajectories were identified: normal (96.7%) and pathologic (3.3%). Compared with the normal trajectory, the pathologic trajectory was associated with an increased risk for preeclampsia (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.6–23.4), increased umbilical artery resistance at 30 weeks of gestation (OR 12.6, 95% CI 4.6–34.1) or 34 weeks of gestation (OR 28.0, 95% CI 8.9–87.7), reduced middle cerebral artery resistance at 30 weeks of gestation (OR 0.33, 95% CI 0.12–0.96) or 34 weeks of gestation (OR 0.14, 95% CI 0.03–0.74), lower gestational age at delivery (mean 32.02 weeks of gestation compared with 38.02 weeks of gestation; P<.001), and higher perinatal complications (OR 21.5, 95% CI 10.5–44.2). In addition, 89.2% of newborns with pathologic fetal growth were admitted to neonatal intensive care units compared with 25.9% of those with normal growth.

CONCLUSIONS: Fetal growth trajectory analysis reliably differentiated fetuses with a pathologic growth pattern among a group of women with growth-restricted fetuses. With further development, this approach could provide clarity to how we define, identify, and ultimately manage pathologic fetal growth.

LEVEL OF EVIDENCE: II

Fetal and maternal leptin in pre-gestational diabetic pregnancy

Objective: To compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. 

Methods: In a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. 

Results: No difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36-1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5-1108.2 pg/mL; type 2 diabetes: 2022 pg/mL, 35.1-1553.3 pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7-810 pg/mL) and type 2 (447.2 pg/mL, 1363-679 pg/mL) diabetes than among women without diabetes (803 pg/mL, 273-623.1 pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=039, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=028, P=0.04).

 Conclusion: Fetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life. (C) 2012 International Federation of Gynecology and Obstetrics. 

Differences in mitochondrial and nuclear DNA status of high-density and low-density sperm fractions after density centrifugation preparation

Background: In order to isolate the â??bestâ?? sperm for assisted conception a discontinuous two-step density gradient centrifugation is usually employed. This technique is known to isolate a subpopulation with good motility, morphology and nuclear DNA (nDNA) integrity. As yet its ability to isolate sperm with unfragmented mitochondrial DNA (mtDNA) is unknown. Methods: Semen was obtained from men (n=28) attending our Regional Fertility Centre for infertility investigations. We employed a modified long polymerase chain reaction to study mtDNA and a modified alkaline Comet assay to determine nDNA fragmentation. Results: The high- density fraction displayed significantly more wild type mtDNA (75% of samples) than that of the low- density fraction (25% of samples). In the high-density fraction, there was a higher incidence of single, rather than double or multiple deletions and the deletions were predominantly small scale (0.1-4.0kb). There was a strong correlation between nDNA fragmentation, the number of mtDNA deletions (r=0.7, p

Cryopreservation of human semen and prepared sperm: effects on motility parameters and DNA integrity

Objective: To investigate effects of cryopreservation on sperm motility and DNA integrity. Design: Pre-cryopreservation and post-cryopreservation analysis of motility and DNA integrity of semen and prepared sperm samples. Setting: A hospital andrology laboratory. Patient(s): Forty men attending the Regional Fertility Centre, Belfast, Northern Ireland. Intervention(s): Each sample was divided, and an aliquot was frozen unprepared. Remaining aliquots were prepared by Percoll density centrifugation (95.0:47.5) or direct swim-up procedure and divided into aliquots to allow direct comparison of fresh and frozen semen and prepared sperm (frozen with or without the addition of seminal plasma) from the same ejaculate. Samples were frozen by static-phase vapor cooling and being plunged into liquid nitrogen. Thawing was carried out at room temperature. Main Outcome Measure(s): Sperm DNA integrity was determined using a modified alkaline single cell gel electrophoresis (comet) assay, and motility was determined using computer-assisted semen analysis. Result(s): Sperm frozen unprepared in seminal fluid appeared more resistant to freezing damage than frozen prepared sperm. Further improvements can be achieved by selecting out the subpopulation of sperm with best motility and DNA integrity and freezing these sperm in seminal plasma, making this the optimal procedure. Conclusion(s): Freezing sperm in seminal plasma improves postthaw motility and DNA integrity.

Economic modelling of antenatal screening and ultrasound scanning programmes for identification of fetal abnormalities

Objective Within the framework of a health technology assessment and using an economic model, to determine the most clinically and cost effective policy of scanning and screening for fetal abnormalities in early pregnancy. Design A discrete event simulation model of 50,000 singleton pregnancies. Setting Maternity services in Scotland. Population Women during the first 24 weeks of their pregnancy. Methods The mathematical model was populated with data on uptake of screening, prevalence, detection and false positive rates for eight fetal abnormalities and with costs for ultrasound scanning and serum screening. Inclusion of abnormalities was based on the relative prevalence and clinical importance of conditions and the availability of data. Six strategies for the identification of abnormalities prenatally including combinations of first and second trimester ultrasound scanning and first and second trimester screening for chromosomal abnormalities were compared. Main outcome measures The number of abnormalities detected and missed, the number of iatrogenic losses resulting from invasive tests, the total cost of strategies and the cost per abnormality detected were compared between strategies. Results First trimester screening for chromosomal abnormalities costs more than second trimester screening but results in fewer iatrogenic losses. Strategies which include a second trimester ultrasound scan result in more abnormalities being detected and have lower costs per anomaly detected. Conclusions The preferred strategy includes both first and second trimester ultrasound scans and a first trimester screening test for chromosomal abnormalities. It has been recommended that this policy is offered to all women in Scotland.

A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia

Background: Mitochondria are vital to sperm as their motility powerhouses. They are also the only animal organelles with their own unique genome; encoding subunits for the complexes required for the electron transfer chain. Methods: A modified long PCR technique was used to study mitochondrial DNA (mtDNA) in ejaculated and testicular sperm samples from fertile men (n=11) and testicular sperm from men with obstructive azoospermia (n=25). Nuclear DNA fragmentation was measured by an alkaline single cell gel electrophoresis (COMET) assay. Results: Wild-type mtDNA was detected in only 60% of fertile mens�??�?�¢?? testicular sperm, 50% of their ejaculated sperm and 46% of testicular sperm from men with obstructive azoospermia. The incidence of mitochondrial deletions in testicular sperm of fertile and infertile men was not significantly different but the mean size of the deletions was significantly less in testicular sperm from fertile men compared with men with obstructive azoospermia (p<0.02). Nuclear DNA fragmentation in testicular sperm from fertile men and men with obstructive azoospermia was not significantly different. Conclusion: Multiple mtDNA deletions are common in testicular and ejaculated sperm from both fertile and infertile men. However, in males with obstructive azoospermia the mtDNA deletions in testicular sperm are of a larger scale.