First-trimester and combined first- and second-trimester prediction of small-for-gestational age and late fetal growth restriction.

OBJECTIVE: To develop a first-trimester or combined first- and second-trimester screening algorithm for the prediction of small-for-gestational age (SGA) and late fetal growth restriction (FGR). METHODS: This was a retrospective study of women with singleton pregnancy, who underwent routine first-, second- and third-trimester ultrasound assessment. Late FGR was defined, at ≥ 32 weeks' gestation in the absence of congenital anomalies, as either (i) estimated fetal weight (EFW) or birth weight (BW) < 3rd centile, or (ii) EFW < 10th centile and either uterine artery mean pulsatility index (UtA-PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile. Neonates with BW < 10th centile, regardless of prenatal parameters, were defined as SGA. The predictive effectiveness of maternal and first- and second-trimester factors was tested using logistic regression and receiver-operating characteristics curve analyses. RESULTS: A total of 3520 fetuses were included (late FGR, n = 109 (3.1%); SGA, n = 292 (8.3%)). Of the late FGR cases, 56 (1.6%) fulfilled the antenatal criteria (EFW < 3rd centile or EFW < 10th centile plus abnormal UtA-PI or CPR) and were defined as prenatally detected late FGR. A first-trimester screening model (comprising conception method, smoking status, maternal height, pregnancy-associated plasma protein-A (PAPP-A) and UtA-PI) could predict 50.0% of the prenatally diagnosed and 36.7% of the overall late FGR fetuses for a 10% false-positive rate (FPR). A model combining first- and second-trimester screening parameters (conception method, smoking status, PAPP-A, second- trimester EFW, head circumference/abdominal circumference ratio and UtA-PI) could predict 78.6% of the prenatally detected, and 59.6% of the overall late FGR fetuses, for a 10% FPR (area under the curve 0.901 (95% CI, 0.856-0.947) and 0.855 (95% CI, 0.818-0.891), respectively). The prediction of SGA was suboptimal for both first-trimester and combined screening. CONCLUSIONS: A simple model combining maternal and first- and second-trimester predictors can detect 60% of fetuses that will develop late FGR, and 79% of those fetuses that will be classified prenatally as late FGR, for a 10% FPR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The utility of artificial neural networks and classification and regression trees for the prediction of endometrial cancer in postmenopausal women.

OBJECTIVE: Artificial neural networks (ANNs) and classification and regression trees (CARTs) have been previously used for the prediction of cancer in several fields. In our study, we aim to investigate the diagnostic accuracy of three different methodologies (i.e. logistic regression, ANNs and CARTs) for the prediction of endometrial cancer in postmenopausal women with vaginal bleeding or endometrial thickness ≥5 mm, as determined by ultrasound examination. STUDY DESIGN: We conducted a retrospective case-control study based on data from analysis of pathology reports of curettage specimens in postmenopausal women. METHODS: Classical regression analysis was performed in addition to ANN and CART analysis using the IBM SPSS and Matlab statistical packages. RESULTS: Overall, 178 women were enrolled. Among them, 106 women were diagnosed with carcinoma, whereas the remaining 72 women had normal histology in the final specimen. ANN analysis seems to perform better with a sensitivity of 86.8%, specificity of 83.3%, and overall accuracy (OA) of 85.4%. CART analysis did not perform well with a sensitivity of 78.3%, specificity of 76.4%, and OA of 77.5%. Regression analysis had a poorer predictive accuracy with a sensitivity of 76.4%, a specificity of 66.7%, and an OA of 72.5%. CONCLUSION: Artificial intelligence is a powerful mathematical tool that may significantly promote public health. It may be used as a non-invasive screening tool to guide clinicians involved in primary care decision making when endometrial pathology is suspected.

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11-13 weeks' gestation. METHODS: This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80-100%) for PE < 32 weeks, 75% (95% CI, 62-85%) for PE < 37 weeks and 43% (95% CI, 35-50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79-96%) for PE < 32 weeks, 75% (95% CI, 70-80%) for PE < 37 weeks and 47% (95% CI, 44-51%) for PE ≥ 37 weeks. CONCLUSION: Assessment of a combination of maternal factors and biomarkers at 11-13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Ovarian tumors: Should the cervix be examined first?

There is a controversy regarding ovarian metastasis in early-stage adenocareinoma of the uterine cervix. The authors present the case of a 5 1-year-old woman that at the time of diagnosis was thought to suffer from a Stage II cervical carcinoma and a synchronous ovarian carcinoma, that turned out to be an ovarian metastasis from the endocervical adenocarcinoma, as attested morphologically, histochemically, and immunohistochemically. Radical hysterectomy with oophorectomy, excision of the omentum, lymph node excision, and cytological sampling of the peritoneal cavity were carried out. It is important to always bear in mind that even low-grade adenocarcinomas of the cervix can be metastatic to the ovaries. Clinicians have to be careful when managing those cases, while further investigation is needed in order to determine the exact mechanism of those metastases and the criteria needed in order to preserve the ovaries in young patients.

Teenage pregnancy antenatal and perinatal morbidity: results from a tertiary centre in Greece.

We present the experience of a tertiary referral hospital in Greece, evaluating obstetric and perinatal outcomes among teenage and average maternal age (AMA) women. We retrospectively assessed all singleton pregnancies during a twelve-month period (January-December 2012). A total of 1,704 cases were reviewed and divided into two groups: one of AMA mothers (20-34 years old) (1,460 women) and the other of teenage mothers (12-19 years old) (244 women). We observed significantly higher incidence rates of preterm births (p < 0.001), preterm premature rupture of the membranes (p < 0.001), gestational hypertension (p < 0.001), preeclampsia (p = 0.043) and Apgar scores < 7 at 5 min (p = 0.015) among teenage mothers. Antenatal surveillance was decreased among teenage mothers (p < 0.001), while rates of anaemia were higher (p < 0.001). Teenage pregnancy is accompanied by significant antenatal and perinatal complications that need specific obstetrical attention. Obstetricians should be aware of these complications in order to ameliorate the antenatal outcome of childbearing teenagers.

Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery.

OBJECTIVE: To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD). DESIGN: Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007. SETTING: A tertiary referral centre for fetal medicine. METHODS: Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis. MAIN OUTCOME MEASURES: The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD. RESULTS: Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median=609 pg/ml, interquartile range: 445.7-782.7) compared to controls (median=322.1 pg/ml, interquartile range: 277.7-414.4), (P<0.001). IL-18 level was also significantly higher (P<0.001) in cases with positive amniotic fluid cultures (median=697.7, interquartile range: 609.0-847.2) compared to those with negative ones (median=330.9 pg/ml, interquartile range: 235.2-440.8). CONCLUSIONS: Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.

The role of three-dimensional imaging in the investigation of IUD malposition.

OBJECTIVES: The aim of this study was to present a systematic review of the use of three-dimensional ultrasound for the detection and evaluation of intrauterine device malposition in a patient of our department. BACKGROUND: Transvaginal sonography failed to detect IUD misplacement in about 9% of cases. Whereas the three-dimensional ultrasound (3D), a new emerging technology, that could provide precise evaluation of IUD malposition. METHODS: The data were extracted from the literature using computerised Medline system. The use-effectiveness and acceptance of three-dimensional imaging in the detection of IUD malposition was examined as an alternative method to two-dimensional ultrasound. RESULTS: Three-dimensional ultrasound was more accurate than two-dimensional for the identifying IUD device. Three-dimensional technique enables assessment of IUD length in the longitudinal section synchronically with imaging arms of the device. Examination with 2D ultrasound is limited to transverse views of the shaft. The arms or other smaller parts cannot be investigated completely because of the frontal view of an IUD is rarely presented. CONCLUSION: Three-dimensional ultrasound is a new and promising imaging tool which provides much better view of the endometrial cavity. This is especially useful in uterus examination and in the detection of IUDs because structures that are not located in one single plane can be imaged simultaneously. Three-dimensional ultrasound is considered to be more secure and safer diagnostic technique to determine the location of IUDs than hysteroscopic evaluation (Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Imperforate hymen with hematocolpometra combined with elevated Ca125.

In the present case, ultrasound examination ruled out the presence of hematosalpinx or other gynecological tumors. This was of great importance to the surgical intervention, especially for avoiding laparotomy. Dilatation of the vagina and uterus, due to imperforate hymen with retrograde menstruation should be considered in the differential diagnosis of abdominal pain in premenarchal girls (Fig. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Uterine prolapse in pregnancy: a rare condition an obstetrician should be familiar with.

Uterine prolapse complicating pregnancy is a rare event. Early recognition is essential in order to avoid possible maternal and fetal risks. We report the case of a 37-year-old pregnant woman who presented to the antenatal outpatient clinic with uterine prolapse at 31(+1) weeks of gestation. Sonographic examination revealed an enlarged fibromatous uterus. She was conservatively treated on an inpatient basis. Two weeks later she underwent an emergency cesarean section because of preterm uterine contractions. A live male neonate weighing 1,900 g was delivered. We believe that conservative management with bed rest, followed by an elective cesarean section, may ensure an uncomplicated gestation and an uneventful delivery.

Screening for pre-eclampsia by oxidative stress markers and uteroplacental blood flow.

Recent evidence suggests that the oxidative stress is an important factor in the pathophysiology of pre-eclampsia. The purpose of this study was to evaluate the possible relationship between increased resistance at the Doppler assessment of the uterine arteries between 20-23 gestational weeks and biochemical markers of oxidative stress, with the development of pre-eclampsia and/or growth restricted infants. This was a prospective study of 34 pregnant women with normal uteroplacental flow and 30 women with abnormal uterine arteries Doppler analysis (mean PI >or= 1.60) during the transvaginal assessment of the uterine arteries at the routine anomaly scan. Blood samples were obtained in order to assess the plasma oxidative stress, namely malondialdehyde (MDA) and uric acid levels. The MDA was significantly higher in the group of women with abnormal uterine arteries Dopplers. This group is at increased risk for the development of pre-eclampsia. The uric acid levels did not differ significantly between the two groups of women. There was no significant difference regarding the sensitivity or the specificity of the uterine arteries Doppler examination in detecting pre-eclampsia in comparison to the combination of oxidative stress and Doppler's. Our study provides additional evidence regarding the role of oxidative stress in the pathophysiology of pre-eclampsia. Whether antioxidant supplementation in the group of women with abnormal uterine Doppler's is effective in reducing the incidence of the disease remains to be established.

Cesarean vs. vaginal birth for term breech presentation in 2 different study periods.

OBJECTIVE: To compare outcomes for fetuses at term in breech presentation during 2 periods when different delivery policies were in effect. METHODS: Outcomes of the 392 planned vaginal deliveries and 1160 elective cesarean sections (CSs) performed from January 1, 1988, through December 31, 2000, were compared with those of the 24 emergency vaginal deliveries, the 403 planned CSs, and 75 emergency CSs performed from January 1, 2001 through December 31, 2004 at Alexandra Hospital, Athens, Greece. RESULTS: A significant difference was found in rates of low 5-minute Apgar score, birth trauma, serious neonatal morbidity, and admission to the neonatal intensive care unit (0% vs. 1.02% [P=0.004], 1.02% vs. 0% [P=0.004], 3.06% vs. 0.43% [P<0.001], and 2.8% vs. 0.43% [P<0.001], respectively) between neonates born by planned vaginal delivery and those born by elective CS during the first period. Only a reduction in rates of admission to the neonatal intermediate care unit was found between the first and second periods. CONCLUSIONS: Planned CS was found to be safer than planned vaginal delivery for fetuses at term in breech presentation. However, the study did not demonstrate that the change in policy improved neonatal outcome.

Low-Grade Appendiceal Mucinous Neoplasm Presenting as an Adnexal Mass.

Appendiceal tumors are rare, late diagnosed neoplasms that may not be differentiated from adnexal masses even by advanced imaging methods and other diagnostic procedures. They may be asymptomatic and remain undiagnosed until surgery. We report a case of an 80-year-old postmenopausal woman presenting with a pelvic mass and a history of weight loss. The patient underwent laparotomy which revealed an appendiceal mucocele, for which she received a full oncological procedure. The histology report showed a low-grade appendiceal mucinous neoplasm, and the patient underwent six cycles of chemotherapy. Appendiceal tumors should be kept in mind in patients with adnexal mass.

Role of the angiopoietin/Tie system in pregnancy (Review).

Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelium-specific receptor tyrosine kinase Tie-2. The angiopoietin/Tie system plays a critical role in the regulation of endothelial cell survival and vascular maturation and stability. Apart from its well-established role in vascular morphogenesis, emerging data support the involvement of angiopoietins in inflammation and various malignancies. Previous studies have underlined the significance of several angiogenic factors in normal placental development. In addition, angiogenic imbalance is observed in pregnancy complications related to impaired placentation, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). However, there is only limited information available on the role of the angiopoietin/Tie system in the establishment of a competent feto-maternal vascular system. In this review, we present the current knowledge regarding the role of angiopoietins in normal pregnancy and pregnancy complications.

Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns.

Undetectable or extremely low levels of circulating immunoreactive parathyroid hormone (PTH) have been reported in human newborns while PTH bioactivity was high. This prompted the hypothesis that the fetal calcemic hormone might be PTH-related protein. The purpose of this study was to measure circulating immunoreactive PTH-related protein in human fetuses and newborns in order to investigate this hypothesis. Parathyroid hormone-related protein (PTHrP(1-86) and intact PTH were measured using two-site immunoradiometric assays in plasma obtained by cordocentesis from 23 fetuses (19-33 weeks of gestation), from 17 newborns at term (38-41 weeks), from their mothers and from 22 normal women of reproductive age. Plasma PTHrP was detectable in all but one of the fetuses and newborns and in all the mothers and the controls. The mean level was similar among fetuses (19-33 weeks) (0.43 +/- 0.18 pmol/l), newborns (0.48 +/- 0.12), mothers (0.48 +/- 0.14) and normal controls (0.46 +/- 0.09). Plasma PTH was found to be significantly higher in fetuses at midgestation (1.0 +/- 0.99 pmol/l) than in the newborns (0.22 +/- 0.21) (p < 0.0025); maternal PTH was significantly higher compared to fetal level at mid-gestation (2.1 +/- 1.0, p < 0.01) as well as at term (2.69 +/- 1.40, p < 0.001). In the control women PTH was 3.07 +/- 1.25 pmol/l. These results showed that plasma amino-terminal PTHrP-(1-86) is detectable during the second half of human fetal life and its level remains unchanged during this period of time, in contrast to changing levels of fetal plasma PTH. The relatively low PTHrP-(1-86) level that we found in the newborns is not responsible for the high PTH-like bioactivity found by some investigators in cord blood at term.

Cardiocentesis: an alternative method of fetal blood sampling for the prenatal diagnosis of hemoglobinopathies.

One hundred fifty-eight cases are reported of fetal cardiocentesis during the second trimester for the prenatal diagnosis of hemoglobinopathies. In all cases, fetal blood sampling by funipuncture was technically impossible or unsuccessful. There were nine fetal deaths possibly related to the procedure, for a total fetal loss rate of 6.5%. If one fetal loss that occurred 46 days after the procedure is excluded, the total procedure-related fetal loss rate is 5.6%. No cases of maternal chorioamnionitis, fetal cardiac trauma, or hemopericardium were encountered among the living infants. We conclude that cardiocentesis should be offered in highly selective cases when funipuncture is not technically feasible. In experienced hands, the procedure has a fetal loss rate of 6.5% with no morbidity among the survivors.

Cervico-isthmic pregnancy: an extremely rare case diagnosed during labour.

This case report describes a cervico-isthmic pregnancy ending in a live vaginal birth at 37+2 weeks' gestation. The case remained undiagnosed throughout pregnancy when after a fairly normal labour a massive haemorrhage occurred. After an unsuccessful effort to control the bleeding conservatively, a total abdominal hysterectomy was carried out. During the operation the diagnosis of cervico-isthmic pregnancy was confirmed, which was in accordance with the pathology report.

Embryo reduction versus expectant management in triplet pregnancies.

OBJECTIVE: In triplet pregnancies, to compare pregnancy outcome of expectant management with that after embryo reduction to twins. METHODS: Retrospective study of 255 trichorionic triplet pregnancies, of which 185 had embryo reduction to twins (reduced group) and 70 were managed expectantly (non-reduced group). RESULTS: Median birth weight was higher by about 500 g and gestation prolonged by about 3 weeks in the reduced pregnancies compared with the expectantly managed pregnancies (2300 vs. 1760 g; 36 vs. 33 weeks). The rates of preterm delivery were significantly lower in the reduced group (11.17 vs. 36.76% for delivery at < or = 32 weeks and 40.58 vs. 83.82% for delivery at < or = 35 weeks, reduced vs. non-reduced group). The percentage of infants born with low birth weight was significantly higher in the expectantly managed triplets (10.98 vs. 28.44% for birth weight < or = 1500 g and 68.55 vs. 92.89% for birth weight < or = 2500 g, reduced vs. non-reduced group). Total fetal loss was significantly higher in the reduced group than in the non-reduced group (15.41 and 4.76%, respectively) and the difference was mainly due to the higher miscarriage rate in the reduced group (8.11 vs. 2.86% in the non-reduced group). With the expected rates of handicap in preterm infants, we would anticipate 0.63% of severely handicapped children due to extreme prematurity in the reduced group and 1.64% in the non-reduced group. CONCLUSION: In triplet pregnancies, embryo reduction to twins significantly reduces the risk of severe preterm delivery and very low birth weight by about one-third, at the expense of a significant increase in total fetal loss, by about one-quarter. The procedure is likely to reduce the risk of having a severely handicapped child due to extreme prematurity.

Pregnancy outcome after multifetal pregnancy reduction.

OBJECTIVE: To study the effects of multifetal pregnancy reduction (MFPR) as a means to reduce the adverse outcome of multiple gestations. METHODS: This was a retrospective study evaluating the outcome of 334 multiple pregnancies after embryo reduction. RESULTS: In 313 multiple pregnancies in which MFPR was performed before 15 weeks, the rates of miscarriage, preterm delivery <33 weeks, preterm delivery <36 weeks and total fetal loss were 9.12%, 13.33%, 38.60% and 16.25%, respectively, and median gestational age at delivery was 35 weeks. There was a significant correlation between miscarriage and the finishing number of fetuses. In 185 triplets reduced to twins, miscarriage, preterm delivery <33 weeks, preterm delivery <36 weeks and total fetal loss occurred in 8.25%, 11.18%, 40.59% and 15.41% of cases, respectively, and median gestational age at delivery was 36 weeks. In the subgroup of 32 reduced triplet pregnancies that also had second-trimester amniocentesis, the risk of miscarriage (3.13%) was not significantly different from that in the rest of the group. Among 21 twin pregnancies that had selective termination at or after 15 weeks, the risk of preterm delivery <33 weeks was three times higher than in the group of 22 twin pregnancies with first-trimester procedures. CONCLUSION: MFPR resulted in at least one live neonate in 83.75% of cases and was effective in reducing the risks of pregnancy loss and severe prematurity in quadruplets and higher-order pregnancies. The risk of miscarriage increased with increasing finishing number of fetuses. In reduced triplets gestation was prolonged in comparison with average figures reported in the literature. In twin pregnancies selective termination in the first trimester carries a lower risk of severe preterm delivery and this emphasizes the need for first-trimester diagnosis.