Clinical Impact of the TCF7L2 Gene rs7903146 Type 2 Diabetes Mellitus Risk Polymorphism in Women with Gestational Diabetes Mellitus: Impaired Glycemic Control and Increased Need of Insulin Therapy.

BACKGROUND: The single nucleotide polymorphism in TCF7L2 rs7903146 is associated with an increased risk of type 2 diabetes mellitus and gestational diabetes mellitus. Mechanisms by which this mutation acts, and its impact on the clinical course of the diseases remain unclear. Here we investigated the clinical impact of the T risk allele in women with gestational diabetes mellitus. METHODS: We genotyped the C/T polymorphism in 164 Caucasian women with GDM (German n=114; Greek n=50). The impact of the T allele on the results of the 75g oral-glucose-tolerance-test, and on the required therapy (diet/lifestyle or insulin) was investigated. RESULTS: During oral-glucose-tolerance-test, women harboring the T allele displayed significantly higher glucose values at 60 min (p=0.034) and were more likely to require insulin therapy even after adjusting for confounders, such as BMI and age. CONCLUSION: These results provide evidence that the T risk allele in TCF7L2 rs7903146 is associated with failure in early postprandial glycemic control and requirement of insulin therapy in women with gestational diabetes mellitus, even after adjusting for confounding factors such BMI and age.

Single nucleotide polymorphisms of Toll-like receptor-4 and of autophagy-related gene 16 like-1 gene for predisposition of premature delivery: A prospective study.

To investigate the impact of carriage of single nucleotide polymorphisms (SNPs) of the Toll-like receptor-4 (TLR4) and of autophagy-related gene 16-like-1 (ATG16L1) in preterm delivery (PTD).A prospective cohort of 145 pregnant women was studied. Women were prospectively followed-up until delivery. Genotyping for rs4986790 (Asp299Gly transition) and rs4986791 (Thr399Ile transition) of TLR4 and for rs2241880 of ATG16L1 was done by PCR-restriction fragment length polymorphism. The primary study endpoint was the impact of carriage of minor alleles of TLR4 on early PTD before gestational week 32. Associations with human chorionic gonadotrophin (hCG) were also analyzed. Peripheral blood mononuclear cells were isolated from 15 healthy women and stimulated for cytokine production.No difference in clinical characteristics was observed between women delivering full term and preterm. The frequency of early PTD was 25% among women carrying minor alleles of TLR4 and 6.8% among women carrying major alleles (P: .032). Odds ratios for PTD were 3.85 among women carrying the GG genotype of rs2241880 and major alleles of TLR4 and 0.26 among carriers of GG genotype and minor alleles of TLR4 (P: .030). The co-presence of GG genotype of rs2241880 and hCG above 70 U/L was an independent variable for PTD. Stimulated production of interleukin-6 was greater among women with GG genotypes of rs2241880.Minor alleles of SNPs of TLR4 predispose to early PTD. The GG genotype of rs2241880 of ATG16L1 is associated with PTD when hCG is supra-elevated.

Methylation profile of genes involved in inflammation, in the blood from pregnancies with maternal preeclampsia due to untreated gestational diabetes mellitus.

PURPOSE: To investigate DNA methylation changes in peripheral blood from patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) due to poorly treated GDM. METHODS: Eighteen pregnant women participated in the study: 6 with GDM, 6 with PE, and 6 healthy controls. The promoter methylation status of genes was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. The results were validated with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Fewer inflammation-related genes were significantly hypomethylated in PE cases compared to healthy subjects than in GDM cases. Some of the examined genes show different methylation patterns between GDM and PE. CONCLUSIONS: The epigenetic changes observed in this study indicate that GDM and PE exhibit specific DNA methylation profiles, with possible clinical applications.

Early changes of the heat-shock protein 60 to 70 ratio as prediction of miscarriage in pregnancy.

PROBLEM: To study the balance of circulating heat shock protein (HSP)60 and HSP70 in pre-term delivery. METHOD OF STUDY: A two-stage approach was used. At first stage, we run retrospective analysis of prospective collected clinical data, and at a second stage, we studied an animal model of pre-term delivery (PTD). Blood samples were collected for prenatal screening in 3629 women. Samples from 23 women with miscarriage before gestational week 21 and 53 well-matched comparators for age, body mass index, parity, and previous miscarriage with full-term pregnancy were depicted. Women with risk factors were excluded. HSP60 and HSP70 were measured by an enzyme immunosorbent assay. PTD was induced after injection of low dose of bacterial lipopolysaccharide; mice were killed for the measurement of HSP60 and HSP70 in blood and tissues. The study endpoint was the association of the HSP60 to HSP70 ratio to miscarriage. RESULTS: A ratio >6 could distinguish between women who will miscarry from women with term pregnancies with sensitivity 60%, specificity 81.8%, positive predictive value 81.8%, and negative predictive value 60% (OR: 6.750, P = 0.025). Mice of the LPS-group PTD had this ratio significantly increased in maternal serum, placentas, and embryos compared to the sham-operation group. Gene expression of hsp60/70 remained in tissues unaltered. CONCLUSION: A HSP60/HSP70 ratio equal to or more than 6 until gestational week 12 is accompanied with great likelihood for miscarriage. A similar ratio applies in an animal model of PTD induced by low-dose LPS.

Placental volume at 11 to 14 gestational weeks in pregnancies complicated with fetal growth restriction and preeclampsia.

OBJECTIVE: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). METHODS: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. RESULTS: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free ß-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P < 0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP-A, ß-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to 14 weeks, PV is an independent predictor of pregnancy complications related to placental insufficiency, and the predictive ability is greater for FGR pregnancies with abnormal fetal Dopplers.

Dehydroepiandrosterone-Sulfate, Insulin Resistance and Ovarian Volume Estimation in Patients With Polycystic Ovarian Syndrome.

Objective: To investigate the potential association of DHEA-S with metabolic and hormonal alterations and with disorders of ovarian morphology. Materials and methods: The present study was based on women with PCOS that attended the Gynaecological Endocrinology - Paediatric and Adolescence Endocrinology Department of our clinic. Overall, 321 patients who met the Rotterdam ESHRE/ ASRM - Sponsored criteria for the definition of PCOS were included. Women's personal medical history was recorded, anthropometric parameters were assessed and blood was drawn for analysis of metabolic and hormonal parameters. A gynaecological ultrasound was also performed to evaluate ovarian morphology. Results: Correlation analysis revealed a significant negative correlation of DHEA-S with the mean volume of the right and left ovary and with the maximum volume of the largest ovary. This finding remained significant after adjusting for age and BMI (ß ± SE = -0.39 ± 0.17, p = 0.023 in the case of mean ovarian volume and ß ± SE = -0.36 ± 0.17, p = 0.032 in the case of the maximum volume of the maximum ovarian volume). Conclusion: The findings of our study reveal a clear negative association of DHEA-S with ovarian volume. To date, however, current evidence in this field are restricted to experimental animal models. Future clinical studies are needed in this field to corroborate our findings.

Hyperandrogenemia in women with polycystic ovary syndrome: prevalence, characteristics and association with body mass index.

BACKGROUND: Hyperandrogenemia is one of the major diagnostic features for the diagnosis of polycystic ovary syndrome (PCOS). The aim of this study was to estimate the prevalence and the characteristics of hyperandrogenemia in women with PCOS and to investigate the association of clinical and biochemical characteristics with body mass index (BMI) according to the presence of hyperandrogenemia. MATERIALS AND METHODS: We studied 266 women diagnosed with PCOS. Hyperandrogenemia was defined by testosterone (T) and/or free testosterone (FT) and/or ∆4 androstenedione (Δ4-A) higher than 75% of the upper limits of each hormone. Patients were stratified in two groups according to a BMI threshold of 25 kg/m2. RESULTS: Hyperandrogenemia was present in 78.2% of the patients. Elevated levels of T were found in 58.4%, while elevated levels of FT and Δ4-A were found in 42.5% and 34.1% of patients. In normal weight women (BMI≤25 kg/m2) with hyperandrogenemia lower values of hip circumference and HOMA-IR and increased levels of T, FT, Δ4-A, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), white blood cells (WBC) and neutrophils were observed compared to women without hyperandrogenemia. Also, in overweight women higher levels of T, FT, Δ4-A, 17-OHP, DHEAS and cortisol were measured, while lower thyroid-stimulating hormone (TSH) levels were comparable to women without hyperandrogenemia. CONCLUSION: This study showed high prevalence of hyperandrogenemia in PCOS women. Women with BMI≤25 kg/m2 have significant differences in androgens, WBC, neutrophils and HOMA-IR and women with BMI≥25 kg/m2 in androgens, TSH and cortisol according to the presence or not of hyperandrogenemia.

Metabolic syndrome in Greek women with polycystic ovary syndrome: prevalence, characteristics and associations with body mass index. A prospective controlled study.

PURPOSE: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI). METHODS: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF). RESULTS: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p < 0.05). Women with PCOS presented statistically higher BMI in comparison with the controls (p < 0.001). Subsequently, the prevalence of MetS was estimated in three groups: normal, overweight and obese subdivided according to BMI. The latter two groups showed significant differences compared with the healthy controls (24.5 vs. 8.8 %, p = 0.050). CONCLUSION: In conclusion, this study showed high prevalence of MetS and increased BMI in Greek PCOS women. In addition, it demonstrated the higher prevalence of MetS in obese PCOS women in comparison with the controls. These results are placing them at increased risk for cardiovascular disease and diabetes in the future and underline the necessity of periodic screening, appropriate diet and exercise program.

Clinical and Biochemical Characteristics in PCOS Women With Menstrual Abnormalities.

Objective: The purpose of the present study was to examine the impact of menstrual cycle abnormalities among patients with polycystic ovary syndrome (PCOS) on biochemical and anthropometric characteristics. Materials and methods: We conducted a prospective observational study of patients 17-35 years of age with PCOS that attended the department of Gynecological Endocrinology of our hospital. Results: A total of 309 women with PCOS participated in the study. In total, 72.2% suffered from menstrual cycle disorders. In our study 15.1% of women were overweight and 24% were obese. Also, 36% of the sample had androgenetic alopecia and 56.4% had acne. According to the stepwise discriminant analysis, we observed that glucose displayed the strongest association to the menstrual status (F to eliminate = 14.13), followed by endometrial thickness (F to eliminate = 10.89), waist circumference (F to eliminate = 10.17), LH levels (F to eliminate = 8.15) and PRL (F to eliminate = 4.45). Significantly higher levels of LH and TSH and lower levels of prolactin were found in women with menstrual disorders compared to those with normal menstrual cycles. Fasting glucose was also considerably higher among these patients although markers of insulin resistance such as the Matsuda, Quicki and HOMA-IR indices did not differ. Conclusion: According to the findings of our study PCOS patients with menstrual disorders exhibit hormonal alterations and elevated fasting glucose. Future studies are needed in this field to corroborate our findings and determine the anthropometric and biochemical profile of patients with menstrual cycle irregularities.

The amount and duration of smoking is associated with aggravation of hormone and biochemical profile in women with PCOS.

We investigated the association between the amount and duration of smoking on biochemical, clinical parameters and the ovarian morphology in women with polycystic ovary syndrome (PCOS). That was a retrospective study. These women were divided into two groups, non-smokers (217) and smokers (92). The amount of cigarettes and duration of smoking was measured in pack-years. Both groups underwent clinical evaluation, biochemical and hormone analysis, transvaginal ultrasound and oral glucose tolerance tests (OGTT). The mean value of the number of cigarettes was 14.8 (±8.8) and the median value of pack-years in the smokers group was 4.0 (1.5-7.5). Smokers group has significantly higher free testosterone (F-T), 17-hydroxyprogesterone (17-OHP), delta 4 androstenedione (Δ4-A), T4, low-density lipoprotein (LDL), and white blood cells (WBC). During correlation of all the above parameters and pack-years, there has been significant positive correlation in F-T and Δ4-A. The participants with more pack-years showed statistically higher values of F-T and Δ4-A. There was also a significant positive correlation between total cholesterol, triglycerides, WBC and pack-years of the participants. Prolactin (PRL) has been inversely associated with pack-years. We concluded that the increase of pack-years aggravated lipid profile, WBC and decreased PRL levels, in PCOS patients.

Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece.

PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions. On the other hand, families with evident aggregation of breast cancer (BC) cases and a BRCA-negative genetic test can still be considered as of elevated risk, since the underlying genetic factor remains unidentified. In the present study, we compared clinical and demographic characteristics between BRCA1 mutation carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients (n=321). METHODS: Data were collected and analyzed from 321 women with BC, with 131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1 and BRCA2. Collected data included demographics, pedigrees, tumor histopathology and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers and grand- mothers were diagnosed at a younger age compared to non-BRCA1-carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative (p<0.01) tumors. The youngest generation was diagnosed with familial breast cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05). Among parous individuals, the number of full-term pregnancies significantly correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their similarities, FBC cases with identified BRCA1 mutations exhibit a clearly distinct profile. We have identified an anticipation effect in FBC patients, with significantly reduced age at diagnosis in younger generations. Increased parity seems to prevent early BC onset. This is the first study comparing clinical and demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.

E-selectin, resistin and reactive oxygen species levels in GnRH -agonist and -antagonist protocols in IVF/ICSI: a prospective cohort study.

PURPOSE: To compare E-selectin, resistin and reactive oxygen species (ROS) levels in serum and follicular fluid (FF) of subfertile women undergoing Controlled Ovarian Hyperstimulation (COH) during IVF/ICSI cycles, using GnRH-agonist and -antagonist protocols. METHODS: In this prospective cohort study, 85 subfertile women undergoing IVF/ICSI were included. Participants underwent the GnRH-agonist and -antagonist protocols; and blood samples were collected at three time points: basic (at start of COH), on the day of hCG and at oocyte retrieval (OR); and from the FF from the first follicle aspirate. Clinical and IVF cycle characteristics, were compared between groups, together with the levels of E-selectin, resistin and ROS in serum and FF, through ELISA. Their prognostic value on pregnancy outcomes was examined. RESULT(S): Examining molecules levels are increasing in serum, from start of COH until OR, irrespectively of the protocol used; FF levels at OR were similar to those in serum at that day. Resistin FF levels were lower in GnRH agonists, compared with the antagonist protocol. Resistin levels at start of COH were associated with clinical pregnancy rates, and this remained significant following adjustment for age, BMI and IVF protocol used, while values of >13.5 ng/ml were associated with a six times greater odd of a pregnancy. CONCLUSION: E-selectin, resistin and ROS levels are increasing during COH, reaching their highest values at OR, with comparable values measured in the FF at that time. Resistin values >13.5 ng/ml are linked with a 6-fold increase on the odds of a pregnancy.

Towards detecting open spina bifida in the first trimester: the examination of the posterior brain.

INTRODUCTION: Our aim was to examine the value of indirect signs of open spina bifida in the mid-sagittal view of the posterior brain at the 11-13 weeks' ultrasound examination and to summarize the current evidence for the first-trimester diagnosis of spina bifida. METHODS: This was a prospective study in routine obstetric population. The presence of four almost parallel lines (four-line view) in the posterior brain was recorded. Biparietal diameter (BPD), intracranial translucency (IT) and cisterna magna (CM) were measured. The ratio of IT to CM (R ratio) was calculated. RESULTS: 2,491 pregnancies were examined prospectively. Updated reference ranges for IT and CM were constructed. There were 3 cases with open spina bifida, and the four-line view was abnormal in 2 of them. The abnormal fetuses had smaller BPD as well as pronounced reduction in the CM and increase in the R ratio. DISCUSSION: Examination of the posterior brain was feasible in all fetuses in the setting of the routine 11-13 weeks' ultrasound examination. Indirect signs of spina bifida are visible in the mid-sagittal view of the posterior brain, and the assessment of these structures can be a reliable tool in the early identification of this abnormality.

Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan.

AIM: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). METHOD: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. RESULTS: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. CONCLUSIONS: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions.

The diagnostic accuracy of E6 & 7 mRNA detection as a primary screening test for the detection of severe cervical lesions.

PURPOSE: This prospective accuracy study aimed to assess the diagnostic accuracy of nucleic acid sequence amplification (NASBA) and flow cytometry for E6/7 human papillomavirus (HPV) mRNA detection as a primary screening test compared to cytology in the triage of severe cervical intraepithelial neoplasia (CIN) lesions. METHODS: 1083 women referred to our outpatient gynecology clinics for a routine Pap test were recruited. Residual material of the Pap smears was tested by NASBA and by flow cytometry for E6/7 mRNA expression. Biopsy results were used as reference standards. The accuracy indices of both techniques and of NASBA type-16 HPV were assessed for the detection of CIN2+ lesions and were compared to cytology. RESULTS: An increased lesion severity was associated with increased positivity rates of both NASBA and flow cytometry tests (x(2), p<0.001). A positive correlation between NASBA and flow cytometry was identified when these methods were examined with the Phi coefficient (value 0.369, 95% confidence interval [95%CI] : 0.307-0.426). Furthermore, NASBA (89.7 vs 57.7%, p<0.0005) and flow cytometry (77.3 vs 57.7%, p<0.0005) exhibited higher specificity rates than cytology. However, their sensitivity rates did not exceed those of cytology (NASBA:69.8 vs 84.6%, p=0.051; flow cytometry: 69.12 vs 84.6%, p=0.043). CONCLUSIONS: Both NASBA and flow cytometry exhibited increased specificity for the triage of CIN2+ lesions. However, their relatively lower sensitivity and higher positivity rates when compared to cytology do not make them ideal for a primary screening test. Hence, the role of mRNA detection in the screening for severe cervical lesions remains to be clarified.

The contribution of sildenafil (Viagra) to ovarian stimulation with gonadotropins in a woman with poor ovarian response.

We aim to present the first case of a pregnancy achieved by administering sildenafil (Viagra) to a woman not responding to controlled ovarian hyperstimulation (COH) with the sole use of gonadotropins. A 37-year-old woman underwent COH, as part of an intracytoplasmic sperm injection (ICSI) cycle, with the combination of r-FSH and HMG for 13 d, without evidence of follicular growth. The addition of oral sildenafil at a dose of 50 mg per day for a total of five doses improved the ovarian response and resulted in the retrieval of 10 oocytes. Three embryos were transferred to the uterine cavity resulting in a successful pregnancy and, eventually, the delivery of a healthy neonate. Conclusively, the use of sildenafil as an adjunct to COH protocols may enhance ovarian response in a woman with poor ovarian response (POR) and merits further research.

Screening for birth weight deviations by second and third trimester ultrasound scan.

OBJECTIVE: The aim of this article was to predict small for gestational age (SGA, at or less than the fifth birth weight percentile) and large for gestational age (LGA, at or greater than the 95th birth weight percentile) fetuses by using maternal and fetal parameters from the second and third trimester ultrasound examinations. METHOD: This article is a retrospective cohort study on 1979 singleton pregnancies that had a routine 20 to 24 weeks anomaly and a 30 to 34 weeks growth ultrasound scans. SGA delivered before 30 gestational weeks were excluded. RESULTS: Second trimester estimated fetal weight (EFW2 ), uterine arteries pulsatility index (PI), and maternal pregnancy characteristics were predictive for SGA (SGA second trimester model: R(2) = 0.225, area under the curve [AUC] = 0.815) and LGA (LGA second trimester model: R(2) = 0.203, AUC = 0.793). Third trimester EFW (EFW3 ), EFW2 , uterine arteries PI2 , umbilical PI, and maternal pregnancy characteristics improved the prediction of SGA (SGA combined model: R(2) = 0.423, AUC = 0.896) and LGA (LGA combined model: R(2) = 0.383, AUC = 0.882). Contingent screening with risk stratification by the second trimester model performed equally well for SGA (AUC = 0.882) and LGA (AUC = 0.861) as the combined models. CONCLUSION: Second trimester model performs well in the prediction of SGA and LGA. The addition of third trimester scan offers substantial improvement. Contingency screening is feasible with similar effectiveness.

Reproducibility study of fetal 3-D volumetry in the first trimester: effect of fetal size and rotational angle of VOCAL software.

Intra- and inter-observer reproducibility of fetal volume measurement by 3-D ultrasound scan (using VOCAL [Virtual Organ Computer-Aided Analysis] software) in 27 fetuses at 7 to 13 wk was studied. For intra-observer variability, the mean difference (MD) and 95% limits of agreement (95% LOA) at 12°, 18° and 30° were MD(12) = 0.097, 95% LOA(12) = -0.87 to +1.06; MD(18) = 0.07, 95% LOA(18) = -1.31 to +1.45; and MD(30) = -0.07, 95% LOA(30) = -1.55 to +1.41. The standard deviation of the differences (SD(DIF)) increased with crown-rump length at 12° (p = 0.0016), 18° (p = 0.0011) and 30° (p = 0.02). For inter-observer variability, MD(12) = 0.15, 95% LOA(12) = -1.65 to +1.95; MD(18) = 0.042, 95% LOA(18) = -1.79 to +1.87; and MD(30) = 0.19, 95% LOA(30) = -1.24 to +1.62. SDDIF increased with crown-rump length at 18° (p = 0.0084) and 30° (p = 0.0073). The accuracy of fetal volume measurement was not influenced by rotational angle or fetal size. Precision deteriorated for wider rotational angles and larger fetuses.

Specific formulas improve the estimation of fetal weight by ultrasound scan.

OBJECTIVE: To develop and evaluate local, sex specific, small for gestational age (SGA) specific, large for gestational age (LGA) specific and combined (biometry, sex and Doppler indices) formulas for ultrasound estimated fetal weight (EFW). METHOD: Low-risk singleton pregnancies that delivered within 7 days from ultrasound examination were assessed. A formula-generating group (1407 pregnancies) and a validation group (469 pregnancies) were created. Fractional regression analysis was used to develop the formulas. Systematic error, random error, fraction within the 10% of actual birth weight and Bland-Altman analysis were used. RESULTS: The local formula and the Hadlock formula with local co-efficients performed better than the Hadlock formula. The SGA-specific formula, the LGA-specific formula and the combined formula had the lower systematic error (MSE: +0.0022291, -0.4226888, +0.8386222, respectively) and the narrower 95% LOA (-292.8 to +292.23, -485.6 to +461.5, -425.7 to +450.46, respectively). The SGA- and the LGA-specific formulas had higher fraction within the 10% of actual birth weight (81.5% and 84%, respectively). CONCLUSIONS: Local formulas improve the EFW calculation. The combined formula can further optimize the accuracy and precision. Application of specific formulas for the small and the large fetus had the most pronounced effect in improving fetal weight estimation.