Mean platelet volume: association with adverse neonatal outcome.

The aim of the study was to investigate on a possible association between maternal mean platelet volume (MPV) and oxygen-metabolic changes in pregnancies affected by altered maternal-fetal Doppler velocimetry. We considered the altered maternal-fetal Doppler velocimetry group (n = 57) pregnant women admitted to our Institution for a pregnancy complication associated to the event Pre-eclampsia (PE) and intrauterine growth retardation (IUGR), with altered Doppler velocimetry in the umbilical artery ( UA) (high pulsatility index, absence or reverse end diastolic flow (ARED), blood flow cephalisation) and/or bilateral increased resistance in uterine arteries. Out of these cases, 25 pregnancies were complicated by PE and 32 pregnancies were complicated by IUGR. We included 145 normotensive third trimester pregnant women as a normal maternal-fetal Doppler velocimetry control group. From all women, 20 ml of whole venous blood was obtained from the antecubital vein soon after Doppler velocimetry evaluation. MPV was significantly higher in women with abnormal Doppler velocimetry compared to those with normal Doppler velocimetry (8.0 fl [7.0-8.7] vs. 9.1 fl [8.0-10.6], <0.001. Values are median [interquartiles]). We performed a ROC curve in order to find an MPV cut-off able to predict an uneventful event in Doppler velocimetry compromised fetuses (neonatal O(2) support > 48 hrs or intubation and/or pH < 7.2 at umbilical blood gas analysis (UBGA)). An MPV > or = 10 fl was significantly related to the former diagnostic endpoints compared to that of non-compromised fetuses (sensitivity: 45%, specificity: 89.7%, 95 CI: 18.8-66, p < 0.01). Our study suggests that pregnancies affected by Doppler velocimetry alterations, an MPV value > or = 10 fl may be associated with severe oxygen support and/or low UA ph at birth.

Nuchal translucency as a predictor of adverse pregnancy outcome.

BACKGROUND: Thickened nuchal translucency (NT) has been related to fetal genetic syndromes, structural abnormalities, and other diseases. The aim of this research was to evaluate the association of NT with adverse pregnancy outcomes. STUDY DESIGN: In the period 2002-2004 in 2104 pregnant women between 10+6 and 13+5 weeks' gestation, NT was evaluated as a parameter for aneuploidy screening: out of these, 734 singleton pregnant women that underwent 2nd trimester amniocentesis and whose pregnancy outcome were known were selected. NT was statistically correlated to pregnancy and neonatal outcome. RESULTS: Median gestational age (GA) at NT evaluation was 11+2 weeks' gestation. NT median was 1.1 mm (0.9-1.4 mm, 25th-75th centile, range 0.5-4.0 mm). After multiple logistic regressions, the variables significantly associated to NT values were: threatened preterm labor (p<0.008) and preterm labor (p<0.02). The best diagnostic accuracy point was NT>95th centile and >1.5 MoM for the prediction of threatened preterm labor. CONCLUSION: In this series, increased NT values were associated to threatened preterm labor and preterm labor in euploid fetuses: this finding may have clinical consequences in the management of such pregnancies.

Doppler velocimetry alterations related to platelet changes in third trimester pregnancies.

The aim of this study was to evaluate the correlations between the haematological parameter mean platelet volume and Doppler velocimetry parameters in order to improve clinical management in third trimester complicated pregnancies (pre-eclampsia, PE, and IUGR) affected by altered uterine resistances. Fifty-one patients were included in the abnormal uterine arteries Doppler velocimetry group (25 pregnancies were complicated by PE, 26 pregnancies were complicated by IUGR). Ninety-nine normotensive pregnant women taking no drugs for at least 2 weeks prior to testing and with no difference in gestational age at evaluation, with normal Doppler velocimetry profiles at routine screen, were used as controls. From all pregnant women, 20 mL of whole blood were obtained into citrate tubes after Doppler velocimetry evaluation and analysed for red blood cell counts (RBC), mean corpuscular volume (MCV), haemoglobin (HGB), haematocrit level (HCT), white blood cells count (WBC), platelet counts (PLT), mean platelets volume (MPV) and other biochemical parameters. From all blood parameters studied, MPV was significantly higher in women with altered uterine artery Doppler velocimetry compared with those with normal Doppler profiles (9.4 +/- 1.0 vs. 8.05 +/- 1.2 fL, P<0.001). In the group with altered uterine artery Doppler velocimetry, pregnancies complicated by PE showed a MPV value higher than pregnancies affected by IUGR (9.5 +/- 1.6 vs. 8.9 +/- 1.1, P<0.001). Finally, mean uterine arteries RI values were significantly related to MPV (fL) in both PE and IUGR groups (P<0.01, r=0.37 and P<0.01, r=0.38, respectively). Our study shows that a periodical monitoring of haematological parameters such as MPV can be associated to Doppler velocimetry in order to improve the management of pregnancies with uterine arteries Doppler velocimetry alterations.

Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus.

OBJECTIVE: To investigate the effectiveness and complication rate of intravaginal gemeprost, a prostaglandin E(1) analogue, for second-trimester pregnancy termination in women with a scarred uterus. METHODS: Of 439 women undergoing induced abortion between the 13th and the 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5 times over 24 h. Those who did not respond received further cycles of gemeprost treatment. RESULTS: The rate of successful abortions among women with uterine scars was not different from that observed in the nulliparous controls, but previously vaginal delivery was associated with a shorter induction to abortion interval. The rate of severe complications did not differ between the groups, and was about 1%. CONCLUSION: The rate of complications following intravaginal administration of a PGE(1) analogue for second-trimester pregnancy termination was similar in women with a scarred or unscarred uterus.

Prognostic value of umbilical-middle cerebral artery pulsatility index ratio in fetuses with growth restriction.

OBJECTIVE: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. PATIENTS AND METHODS: Seventy-two pregnant women with fetuses showing growth restriction and delivered within 48 h of their last Doppler velocimetry evaluation. The last computerized cardiotocographic trace from these fetuses was used for statistical analysis, and the last trace from the healthy fetuses of 93 consecutive women undergoing cesarean section was used as control. Umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), UA PI/MCA PI ratio, and uterine artery resistance index (Ut RI) were assessed. RESULTS: Among women with growth-restricted fetuses, all parameters were significantly higher in those who had hypertension; and in those who had diabetes, only the UA PI/MCA ratio was significantly higher. Umbilical artery PI values and the UA PI/MCA ratio were higher in those who had a nonreassuring result to computerized nonstress test immediately before delivery. A multiple logistic analysis showed that the UA PI/MCA ratio was the only Doppler velocimetry parameter predicting cardiotocographic nonreactivity; furthermore, the predictivity of extended newborn hospitalization (longer than 15 days) was verified, with a sensitivity of 56% and a specificity of 92% when the ratio was higher than 1.26. CONCLUSION: The MCA PI of fetuses with growth restriction should be assessed. The UA PI/MCA ratio is predictive of a nonreactive computerized cardiotocography trace and of prolonged neonatal hospitalization.

Is delayed childbearing changing gene frequencies in Western populations?

Experimental data and clinical observations suggest that delaying childbearing influences the biology of the mother-fetus relationship, with a negative effect on fetal development and predisposition to severe diseases such as type 1 diabetes. We reason that advanced maternal age may influence intrauterine selection, favoring genotypes that are more adapted to the intrauterine environment of less young women. In the present study we have investigated the relationship of maternal age to HP genotype and PGM1-Rh area (chromosome 1) that have been previously found to be associated with fertility and developmental parameters. HP phenotype was determined in 679 consecutive puerperae from the population of central Italy. PGM1 phenotype and Rh C phenotype were determined in 222 puerperae and 200 newborns. The HP 1,1 phenotype decreases and the HP 2,2 phenotype increases with maternal age. The proportion of phenotypes carrying both the Rh C and PGM1*1 alleles is much higher in puerperae older than 36 years than in puerperae of age 22 years. The frequency of the PGM1*1-Rh C haplotype increases and the frequency of the PGM1*2-Rh C haplotype decreases with maternal age. The changes in these genetic systems with advancing maternal age are similar in mothers and newborns. The delay of childbearing age, associated in Western countries with the fertility transition in addition to detrimental effects on intrauterine development and increased susceptibility to severe disorders, could bring about changes in the genetic composition of a population.

Asymptomatic struma ovarii: a case report.

Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign, although malignant transformation has been reported. The preoperative diagnosis is generally difficult. Thyroid hormones may be produced and in a few cases asymptomatic women may develop definitive clinical hypothyroidism after resection of struma ovarii. We report a case of a 39-year-old woman who underwent laparoscopic resection of an asymptomatic right ovarian mass. The pathologic diagnosis was struma ovarii. The postoperative period was uneventful and her thyroid function remained normal.

Antenatal corticosteroids policies in 14 European countries: factors associated with multiple courses. The EURAIL survey.

AIM: To describe antenatal corticosteroids (ANCs) policies in European obstetric units and to determine factors that influence the use of multiple courses. METHODS: 641 obstetricians from obstetric departments covering a geographical area in 14 European countries responded to a questionnaire on ANCs policies. Logistic regression was used to identify factors that were related to the use of multiple ANCs courses. RESULTS: The survey response rate was 76% (inter-country range 33-94%): 11% (0-50%) of the respondents started ANCs from 23 to 24 wk gestation, 82% from 24 to 28 wk (50-100%) and 7% from 28 to 36 wk (0-32%). Eighty-five percent of the units (63-100%) used multiple ANCs courses. After adjustment for country, number of infants delivered at 24-32 wk annually in the unit, NICU and maternal hypertension, maternal hypertension tended to be an explicative factor (OR 1.97; 95% CI: 0.75-5.17). CONCLUSIONS: The high proportion of departments that initiated ANCs between 24 and 28 wk of gestation is consistent with the high incidence of neonatal morbidity and mortality in that age range. Multiple courses are overwhelmingly prescribed in Europe, although their risk/benefit ratio compared with a single dose is not yet known. The likelihood of using repeated courses of ANCs may be related to the presence of maternal hypertension, and this highlights the importance of closely monitoring women at risk of premature delivery.

Maternal cigarette smoking, metabolic enzyme polymorphism, and developmental events in the early stages of extrauterine life.

The recent observation that maternal ACP1 genotype has an interactive effect with smoking on intrauterine development prompted us to search for a possible interaction effect between smoking and ACP1 genotype on haptoglobin (Hp) development in the neonatal period. ACP1 is a highly polymorphic protein tyrosine phosphatase involved in signal transduction of several growth factor receptors. The enzyme is composed of two isoforms, F and S. We studied 299 infants born in the Department of Obstetrics of the University Hospital of Rome La Sapienza. We found that an interaction between ACP1 genotype and smoking has an effect on haptoglobin development: A significant delay of haptoglobin development in infants born to smoking mothers is observed only in infants with the ACP1 *B/*B genotype, which shows the highest concentration of the ACP1 F isoform. The results indicate that the ACP1 genotype modifies the deleterious effects of smoking on development not only during intrauterine life but also during the early stage of extrauterine life.

Computerized cardiotocography in the management of intrauterine growth restriction associated with Doppler velocimetry alterations.

OBJECTIVE: To verify the reliability of computerized cardiotocography (cCTG) in the prediction of the oxygen metabolism status of fetuses with growth restriction and Doppler velocimetry alterations. METHODS: From 24 third-trimester cesarean section performed because of intrauterine growth restriction (IUGR) and Doppler velocimetry alterations, there were 11 cases of fetal heart rate alterations (Dawes-Redman criteria were not satisfied) and 13 cases of reactive cCTG. Fetal lung maturity was detected by amniocentesis and blood samples for umbilical blood gas analysis (UBGA) were collected before the first neonatal breath from the umbilical artery in a double-clamped segment of the cord. RESULTS: Umbilical cord gas analysis showed arterial cord blood pH to be 7.20 or less in 11 newborns (45.8%), 7.10 or less in 6 (25%), and 7.00 or less in 3 (12.5%). Linear regression analysis showed short-term variation (STV) in the fetal heart rate to be significantly correlated with umbilical artery pH (r = 0.49; P = 0.01) and pCO2 (r = -0.50; P = 0.01). There were no significant correlations between cCTG and the other UBGA parameters considered. Receiver operator curves permitted to calculate the STV values at which pathological neonatal UBGA values can be expected (pH < 7.00 and pCO2 > 80 mmHg). A short-term variation less than 4.5 ms was found to predict acidemia with a sensitivity of 100% and a specificity of 70% (positive predictive value, 33%; negative predictive value, 100%), and hypercarbia with a sensitivity of 100% and a specificity of 77.8% (positive predictive value, 55.6%; negative predictive value, 100%). CONCLUSION: In view of the results of this study, 4.5 ms for STV may be a threshold below which timing of delivery should be decided in cases of fetal growth restriction.

Three-dimensional sonography and hysterosalpingosonography in the diagnosis of uterine anomalies.

Uterine anomalies implicated in female subfertility, implantation failure and miscarriages can often be detected often by two-dimensional transvaginal (2D TV) ultrasound scanning. When used as a screening test TV ultrasound has provided sensitivity rates of up to 100% about uterine anomalies. Improved depiction has been achieved with the development of hysterosalpingosonography (HSSG). The anechoic interface provided by the saline solution allows the examiner to determine whether an abnormality is intracavitary, endometrial, or submucosal. The aim of this study was to evaluate the role of 2D TV contrast sonography and 3D TV ultrasound in the diagnosis of congenital uterine anomalies in comparison with their appearance of hysterosalpingosonography findings.

Severe hypoplasia of the right femur, ipsilateral agenesia of the fibula and twisted right foot in a 24-week-old fetus with proximal femoral focal deficiency (PFFD).

A case of a 24-week-old fetus of non consanguineous parents with an ultrasonographic diagnosis of a short right femur, ipsilateral agenesia of the fibula and a twisted right foot is described. Cordocentesis revealed a normal 46XY karyotype. The parents were informed on treatment options and after psychological counselling they decided to undergo an abortion. Post mortem examination confirmed the diagnosis of a severe right limb malformation.

Ultrasonographic patterns of fetal breathing movements in normal pregnancy.

OBJECTIVE: To assess through pregnancy fetal breathing movements (FBMs) patterns detected by M-mode and Doppler velocimetry technology. METHODS: In this cross-sectional study FBMs were investigated in 1882 uncomplicated pregnancies over a 4-year period. Abdominal and thoracic wall movements of fetuses between 14 and 40 weeks of gestation were studied by M-Mode scan, and color Doppler velocimetry with spectral imaging analysis was used to investigate the presence of FBMs associated with nasal fluid flow velocity waveforms (NFFVWs). RESULTS: Abdominal movements were observed in 19% of cases when gestation was less than 20 weeks and in 61% of cases when it was between 21 and 25 weeks; chest movements were significant after 21 weeks; and NFFVWs were detected at 22 weeks and increased progressively to 93% of cases at term. CONCLUSIONS: Fetal breathing movements are a complex phenomenon with a composite, progressive pattern of development during gestation.

Maternal nitric oxide supplementation increases adrenomedullin concentrations in growth retarded fetuses.

Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of fetoplacental circulation in human pregnancy. The aim of this study was to investigate the effect of maternal NO supplementation in pregnancies complicated by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM concentrations and their correlation with uteroplacental and fetal blood flow. We studied 20 pregnant women with IUGR and impaired uteroplacental blood flow between 27 and 35 weeks of gestation randomly selected to receive either transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM concentrations did not change before and after NO treatment. AM levels were significantly higher in growth retarded fetuses whose mothers received NO donors (114.1 +/- 17.6 pg/ml) than in untreated fetuses (59.8 +/- 38.6 pg/ml), whereas NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated with middle cerebral artery pulsatility index in untreated IUGR but not in NO treated pregnancies.

Reproductive outcome after laparoscopic treatment of endometriosis.

PURPOSE OF INVESTIGATION: To evaluate the pregnancy rate after laparoscopic treatment of endometriosis. PATIENTS AND METHODS: 47 infertile women undergoing laparoscopic treatment of endometriosis. RESULTS: rAFS stage was as follows: 11% of patients had Stage I, 11% Stage II, 53.3% Stage III and 24.4% Stage IV. The mean duration of follow-up was 48.5 +/- 18.44 months. The overall pregnancy rate was 64.4%. Eighteen out of 26 women (69%) became pregnant within six months after laparoscopy, 23% at 12 months, 11% within 24 months, and 11% after two years (p < 0.01). Adnexal adhesions and tubal status significantly affected the pregnancy rate. No differences were found regarding the stage of disease and the presence of ovarian endometriomas. CONCLUSION: Laparoscopic treatment of endometriosis enhances fertility and the pregnancy rate is highest within the first six months after surgery. Adnexal adhesions and tubal conditions influence the reproductive outcome.

Cytologic endometrial surveillance in tamoxifen-treated women.

The authors report the results of a study conducted on 136 patients affected by breast cancer under treatment with tamoxifen at a daily dose of 20 mg who underwent a strict follow-up including endometrial surveillance. The cytologic evaluation of the endometrium was performed on smears obtained by the endocyte sampling. The results were in accordance with what is reported in the literature. Forty cases presented with hyperplasia which was atypical in two cases. Only in one case did histology show a well differentiated adenocarcinoma. In 25 cases the endometrium resulted to be proliferative in accordance with the effect of tamoxifen, while the remaining 67 cases were atrophic. The investigation was not possible in four cases due to stenosis. In our study the endocyte sampler resulted to be an economic, simple and painless cytologic device, suitable for clinical use because of its low incidence of false positives.

The effects of fetal breathing movements on the utero-fetal-placental circulation.

Important factors which may affect the fetal circulation are the fetal breathing movements (FBMs) and other movements adn the features of fetal circulation. Recent studies have demonstrated that FBMs are a normal phenomenon of intrauterine development and that there are two patterns of FBMs: (1) A predominant pattern of rapid, irregular (in rate and amplitude) episodic movements, with interspersed episodes of apnea that is present more than 50 percent of the time and accounts for more than 90 percent of the breathing activity. Interestingly, periodic sighs are often seen during these FBMs; (2) There is also a less frequent pattern of sporadic, slow (1 to 4 movements/min), deep inspiratory movements, like sighs or gasps, or espiratory efforts which resemble grunting, coughing, or panting. The first pattern, which represents normal fetal respiratory activity, only occurs during rapid eye movements (REM) sleep, and it is unrelated to changes in blood gases and pH values and to afferent impulses from aortic and carotid bodies; FBMs may produce intrathoracic pressure swings of 35 Torr or more and are independent of Hering-Breuer reflexes. This pattern is usually accompanied by increased FHR beat-to-beat variability and increased systolic and diastolic blood pressure and flow (BF). Therefore, they may influence the velocimetry of B.F. in humans, e.g., RED and ARED in the umbilical artery blood flow (UABF), which do not necessarily indicate impending fetal demise. The second pattern is unrelated to the fetal behavioral state and blood gas tensions. Concerning the effects of drugs on FBMs, we have analysed the effects aminophylline (A)(bolus of 240 mg followed by 0.2 mg/kg/min) given to women not in labor; A caused a prompt and sustained FBMs that started as vorteces and then as regular inspiratory and expiratory movements, which increased in frequency (up to 88/min) and depth. Hexoprenaline given to pregnant women with threatened preterm labor were able to elicit FBMs and NFFV; the infusion of 0.3 microg/min increased UABF. Conjugated estrogens administered to the mother as a 10 mg bolus enhanced FBMs, as documented by TM and nasal flow velocity waveforms (NFFV); this was associated with an increased UABF; betamethasone (4 mg bolus to the mother) was shown to induce FBMs and an increased UABF. In a twin pregnancy betamethasone (0.5 mg/kg) was administered IV into the umbilical vein in one fetus and IM to the other; in both cases bradycardia and increase in UABF occurred, immediately after IV infusion, and after 30 min following IM injection FBMs were induced or enhanced in frequency and depth. The flow in MCA was unchanged. In conclusion, the fetal circulation is influenced by fetal behavioural states, particularly by FBMs that affect the fetal cardiovascular function, including blood pressure and FHR thereby conditioning the velocimetric response of its major vessels, i.e., UA and MCA BF, whose alterations do not necessarily reflect impending fetal demise.