Maternal C-reactive protein at hospital admission is a simple predictor of funisitis in preterm premature rupture of membranes.

AIM: To analyze the prognostic value of maternal serum C-reactive protein (CRP) in predicting funisitis in patients with preterm premature rupture of membranes (pPROM). METHODS: 66 patients (gestational age 24-33 weeks) hospitalized 1-12 h after pPROM were enrolled. White blood cell count (WBC), platelet count (PLT) and plasma concentration of CRP were assessed every 3 days. Histological evidence of chorioamnionitis and funisitis was obtained post-partum. Receiver operating characteristic (ROC) curves were employed to evaluate the role of maternal CRP in predicting funisitis. RESULTS: Funisitis was found in 24 patients (36.3%); 42 patients (63.7%) without funisitis were considered as controls. PLT and WBC at admission and before delivery did not show significant differences and were not statistically different between the two groups. Patients with funisitis had significantly higher CRP levels both at admission to hospital and 24- 48 h before delivery. ROC curve analysis showed that CRP at admission (area under the curve: 0.671, p = 0.021) and before delivery (area under the curve: 0.737, p = 0.001) are predictive of funisitis. CONCLUSIONS: High maternal serum CRP levels (>20,000 µg/l) in pPROM patients at admission to hospital may be an early marker which indicates, with a good diagnostic performance, the presence of funisitis.

Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy--a case-control study of the outcome in children.

BACKGROUND: Primary cytomegalovirus (CMV) infection early in gestation causes severe disease. METHODS: Case patients were 32 congenitally infected children aged 1-5 years who had either hearing deficit and/or psychomotor retardation and whose mothers had a confirmed or probable primary CMV infection at ≤ 20 weeks' gestation. Control subjects were 32 congenitally infected normal children whose mothers had a confirmed primary infection at ≤ 20 weeks' gestation. Case patients and control subjects were matched by the weeks of maternal gestation (± 1 week) at the mother's infection and by the child's age (± 1 year) at evaluation. RESULTS: For the case patients and control subjects, the mean age was 3.0 years. The mean number of weeks of gestation at maternal infection was 11 weeks. The only risk factor for an affected child was the mother not receiving immunoglobulin (P = .001). Of the 32 case patients, only 4 mothers received CMV immunoglobulin, compared with 27 of the 32 mothers of control infants (adjusted odds ratio, 14 [95% confidence interval, 1.7-110]). The rate of both psychomotor retardation and hearing deficit decreased with immunoglobulin. CONCLUSIONS: These results support the efficacy of immunoglobulins for decreasing the severity of disabilities caused by fetal CMV infection after a primary maternal infection during pregnancy.

Role of the infections in recurrent spontaneous abortion.

Embryo-fetal infections have been reported to cause recurrent spontaneous abortions (RSAs) at a rate lower than 4%. The possible mechanisms include production of toxic metabolic byproducts, fetal or placental infection, chronic endometrial infection, and chorio-amnionitis. Viruses appear to be the most frequently involved pathogens, since some of them can produce chronic or recurrent maternal infection. In particular, cytomegalovirus during pregnancy can reach the placenta by viremia, following both primary and recurrent infection, or by ascending route from the cervix, mostly following reactivation. Another herpesvirus, herpes simplex virus type 2, less frequently type 1, causes recurrent infections of the genital tract, which can involve the feto-placental unit. Parvoviruses have also been implicated in the development of repeated fetal loss. Among bacterial infections, Chlamydia trachomatis, Ureaplasma urealyticum,and Mycoplasma hominis have been mostly associated with occurrence of RSA. An increased risk of abortion among women with bacterial vaginosis (BV) during early pregnancy was also shown, but questions arise about the role of chronic BV in its occurrence. Although a definitive relationship between recurrently active infections and RSA is still lacking, mostly due to difficulties in demonstrating the pathogenic role of each individual isolated pathogen, diagnosis and therapy of RSA-related infections should be attempted. The diagnosis of infectious agents as a possible cause of RSA might lead to a therapeutic approach with antiviral drugs and antibiotics or using immunoglobulins, which can display both anti-infective neutralizing and immunomodulating properties.

Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection.

Human cytomegalovirus (HCMV) is the major viral cause of birth defects worldwide. Affected infants can have temporary symptoms that resolve soon after birth, such as growth restriction, and permanent disabilities, including neurological impairment. Passive immunization of pregnant women with primary HCMV infection is a promising treatment to prevent congenital disease. To understand the effects of sustained viral replication on the placenta and passive transfer of protective antibodies, we performed immunohistological analysis of placental specimens from women with untreated congenital infection, HCMV-specific hyperimmune globulin treatment, and uninfected controls. In untreated infection, viral replication proteins were found in trophoblasts and endothelial cells of chorionic villi and uterine arteries. Associated damage included extensive fibrinoid deposits, fibrosis, avascular villi, and edema, which could impair placental functions. Vascular endothelial growth factor and its receptor fms-like tyrosine kinase 1 (Flt1) were up-regulated, and amniotic fluid contained elevated levels of soluble Flt1 (sFlt1), an antiangiogenic protein, relative to placental growth factor. With hyperimmune globulin treatment, placentas appeared uninfected, vascular endothelial growth factor and Flt1 expression was reduced, and sFlt1 levels in amniotic fluid were lower. An increase in the number of chorionic villi and blood vessels over that in controls suggested compensatory development for a hypoxia-like condition. Taken together the results indicate that antibody treatment can suppress HCMV replication and prevent placental dysfunction, thus improving fetal outcome.

Review and meta-analysis: Benefits and risks of multiple courses of antenatal corticosteroids.

BACKGROUND: Preterm birth causes infant morbidity and mortality. A single course of antenatal corticosteroids (ACS) should be considered routine for preterm delivery. Benefits of therapy before 34 weeks' gestation have been established for infants born between 24 h and 7 days after treatment. It is still unclear whether multiple courses (MC) of ACS should be performed in women at risk of preterm delivery 7 days or more after initial treatment. OBJECTIVES: To determine the risks and benefits of MC of ACS. METHODS: Search and selection for human randomized controlled trials were conducted in PubMed and The Cochrane Central Register of Controlled Trials. Statistical analysis was performed using the Review Manager 4.3 software. MAIN RESULTS: MC of ACS were associated with a statistically decrease in the occurrence of respiratory distress syndrome, patent ductus arteriosus, use of surfactant, ventilation support, and any maternal side effects. This treatment was also associated with a significant reduction in birth weight and head circumference. CONCLUSIONS: MC of ACS in women at risk of preterm birth do not offer significant benefits concerning the composite neonatal morbidity. Data on long-term safety are still insufficient. Further evaluations, most by follow-up studies, are required to study the long-term effects.

Transplacental transfer of antiretroviral drugs and newborn birth weight in HIV-infected pregnant women.

Although it is well known that antiretroviral drugs (ARVs) across the placenta in different extents, few data are available concerning the impact of the transplacental passage of ARVs on newborn outcome. The aim of this study is to evaluate the transplacental diffusion of ARVs and the clinical assessment of the newborn. Mother and cord lopinavir, nelfinavir, atazanavir and nevirapine plasma levels were determined by high-performance liquid chromatography. Newborn gestational age, weight, and Apgar score were recorded. Cord-to-mother ratio (C:M) was calculated to estimate the placental passage of ARVs. Preterm birth was defined as delivery at <37 weeks of gestation and low birth weight was defined as a birth weight of <2500g. Twenty-six HIV-infected pregnant women were enrolled. Nevirapine presented the highest C:M ratio (0.60 +/- 0.19), the C:M ratio of nelfinavir and atazanavir was 0.37 +/- 0.38 and 0.20 +/- 0.14, respectively. The lopinavir level in the cord was undetectable. The observed prevalence rate of neonatal low birth weight and preterm delivery was 19,2% (n = 5) and 15.4% (n = 4), respectively. A significant linear regression analysis was reported between the C:M ratio and newborn birth weight (p = 0.01). Although the role of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission is indisputable, these data indicate a pharmacological rationale to the association between birth weight and highly active antiretroviral therapy during pregnancy.

Guidelines on CMV congenital infection.

Congenital cytomegalovirus (CMV) infection occurs in 0.6-0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

Validity of amniotic fluid index in preterm rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (pPROM) complicates up to one-third of preterm deliveries. We studied the Amniotic Fluid Index (AFI) in order to ascertain its validity as a predictive variable of maternal-fetal outcome in pregnancies complicated by pPROM. STUDY DESIGN: One hundred and fourteen pregnant women with gestational age between 24 and 34 weeks' gestation at the time of pPROM. Patients were categorized into two groups on the basis of AFI value (AFI <5 cm=63 or AFI >or=5 cm=51) performed at the time of admission. RESULTS: AFI numeric values were significantly related to the following maternal-neonatal variables: high maternal body temperature (P7 at 5 min (P

The combined effect of betamethasone and ritodrine on the middle cerebral artery in low risk third trimester pregnancies.

AIMS: To evaluate the effect of antenatal betamethasone and ritodrine in third trimester low risk singleton pregnancies by Doppler technology. SUBJECTS AND METHODS: Eighty-four third trimester pregnant women who received a full course of betamethasone and delivering uneventfully were recruited. The Doppler examination included the assessment of the pulsatility index (PI) of the umbilical artery (UA PI) and the middle cerebral artery (MCA PI) prior to treatment (baseline), and 48, 72 and 96 h after the second dose of betamethasone. RESULTS: No significant difference was found in UA PI and UA/MCA values following betamethasone therapy. In contrast, MCA PI decreased significantly 48 h from the last injection of betamethasone in the whole study group (P<0.001), and returned to basal values at 96 h. We also found that MCA PI was reduced significantly at 48 h in the subgroup under tocolysis (n=41) and in the subgroup not receiving tocolysis (n=43). We compared MCA PI values for both subgroups in the four timings, and found a non-significant difference comparing baseline and 96 h values. However, when comparing MCA PI values after 48 and 72 h, significantly lower differences in PI values in both subgroups were found. CONCLUSION: In low risk pregnancies, betamethasone therapy in the third trimester is related to a significant but transient reduction of MCA PI, which is more pronounced during tocolytic therapy. Although the physiological basis of this effect is currently unclear, it could be related to the local regulation of intracerebral blood flow.

Structural-tridimensional study of yolk sac in pregnancies complicated by diabetes.

OBJECTIVES: To assess by two- and three-dimensional ultrasound the diameter and volume of the yolk sac in pregnant women affected by type 1 diabetes during the first trimester of pregnancy. METHODS: 18 women affected by insulin-dependent diabetes mellitus (IDDM) and 52 normoglycemic pregnant women (controls) were enrolled in this study. The women were evaluated once a week (5-12 weeks of pregnancy). Ultrasound examination in all pregnant women was initially performed in a bidimensional fashion with a transvaginal 6.5-MHz probe and subsequently using a three-dimensional technique. RESULTS: In the pregnant diabetic women the diameter of the yolk sac was significantly higher than that of controls in the first weeks of pregnancy, reaching a maximum diameter at 9 weeks, and decreasing thereafter, earlier than controls. The volume of the yolk sac increased in both groups from 5 weeks of pregnancy and reached maximum values at 10 weeks in both groups. The volumetric increase and decrease after reaching highest values were greater in IDDM patients. CONCLUSION: The clinical and diagnostic implications of the results of this study are still to be defined. Such a diagnostic technique may prove to be an additional element in monitoring diabetic women during early pregnancy.

Amniotic fluid lamellar body counts for the determination of fetal lung maturity: an update.

AIM: To reassess the cut-off value for lamellar body counts (LBs) for fetal lung maturity (FLM) over a 10-year study period. PATIENTS AND METHODS: 178 pregnancies were selected under strict inclusion criteria and delivered within 48 h from amniocentesis. FLM was determined by amniotic fluid LBs in centrifuged samples (300 x g for 10 min) in a commercially available Coulter Counter. Cases beyond 37 weeks were excluded. RESULTS: Mean gestational age was 33.5+/-3.0 weeks at amniocentesis and 33.7+/-3.0 weeks at birth. After reassessing the best compromise between sensitivity and specificity for all cases using the receiver operating characteristic (ROC) procedure, an FLM cut-off value of < or = 22,000/microL was obtained. Diagnostic accuracy (and confidence interval, CI) was: sensitivity, 73% (60.0-83.6%); specificity, 81.7% (CI 73.6-88.1%); positive predictive value, 66.2%; and negative predictive value, 86.0%. CONCLUSION: No significant change in FLM cut-off for LBs was found when comparing the value from this study and the results of our earlier report presented in 1996 (< or = 22,000 vs. < or = 20,000/microL), although the new value may be more accurate, since it is based on neonatal outcome with the exclusion of cases in which the diagnosis of FLM is seldom warranted, i.e., > 37 weeks' gestational age.

Computerized cardiotocography parameters in pregnant women affected by pregestational diabetes mellitus.

AIM: To evaluate whether computerized CTG (cCTG) is a reliable method of predicting neonatal outcome in pregnancies complicated by pregestational diabetes at term. PATIENTS AND METHODS: We considered 27 pregnant women affected by pregestational diabetes and 46 normal pregnancies as controls that fulfilled the following criteria: singleton, Caucasian, euglycemic pregnancies at term (>37 weeks gestational age). All women delivered by cesarean section (CS), with an antepartum cCTG performed within one hour before the CS and an UBGA available at birth. No patient was in labor during FHR monitoring. RESULTS: Among cCTG parameters, accelerations 15 bpm, HV min, HV ms and STV were significantly lower in comparison to controls. We observed that in the diabetic pregnant women the parameter STV was not able to predict or to linearly regress with the most important UBGA parameters: pH and pCO2. Contrarily, in normal pregnancies, the STV linearly regressed with both the pH (p < 0.03) and pCO2 (p<0.04). CONCLUSIONS: Computerized FHR criteria may not be applicable to fetuses in pregestational diabetic pregnancies at term. Therefore some criteria should perhaps be modified for a correct interpretation of cCTG in these pregnancies.

Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection.

OBJECTIVE: To compare the clinical manifestations and laboratory abnormalities associated with primary cytomegalovirus (CMV) infection in pregnancy with recurrent and non-active CMV infection (controls). DESIGN: A prospective cohort study. SETTING: Rome, Latium and other Italian regions. POPULATION: Three hundred and sixteen pregnant women with CMV infection: 102 had primary infection, 105 had recurrent infection and 109 with non-active infection were followed up as controls. METHODS: CMV diagnosis was based on serological examinations (CMV IgG, IgM and IgG avidity) and detection of CMV DNA by polymerase chain reaction in maternal serum, urine and cervical samples. The clinical history and laboratory evaluations were carried out at enrollment and at each subsequent visit, every one to three months. MAIN OUTCOME AND MEASURES: Identification of clinical and laboratory indicators of primary CMV infection in pregnancy. RESULTS: Compared with women with recurrent or non-active infection, women with primary infection had a statistically significant higher prevalence of fever, asthenia, myalgia and flu-like syndrome (P < 0.001). In particular, relevant symptomatology was observed in 32 women (31.4%), of whom 25 had flu-like syndrome and 7 persistent fever as a single manifestation. Moreover, women with primary infection showed a significantly increased rate of lymphocytes >or=40% (39.2% vs 5.7% or 3.7%, respectively, P < 0.001) and elevated aspartate aminotransferase and/or alanine aminotransferase levels (35.3% vs 3.9% or 0.9%, respectively, P < 0.001): lymphocytosis and/or increased aminotransferases occurred in 53 patients (52%). In total, clinical manifestations and/or laboratory abnormalities occurred in 61 women with primary infection (59.8%) compared with 20 with recurrent infection (19%) and 13 controls (11.9%) (P < 0.001). CONCLUSION: Clinical manifestations (i.e. flu-like syndrome, fever) and abnormal laboratory findings (i.e. lymphocytes >or=40%, elevated aminotransferases) may suggest the presence of primary CMV infection and should prompt subsequent virological investigations.

Validity of short term variation (STV) in detection of fetal acidemia.

AIMS: We aimed to establish a cut-off for short term variation (STV) in msec in electronic FHR tracings as a single parameter for the prediction of neonatal acidemia and hypercarbia at birth. METHODS: 195 consecutive cases of singleton pregnancies between 26 to 42 weeks' gestation delivered by cesarean section, with an antepartum tracing performed within 4 hours from birth and umbilical artery gas analysis (UBGA) available at birth. RESULTS: A positive correlation (r = 0.27, p < 0.0001) was found when STV was regressed against gestational age. We also found significant correlations between STV and UBGA parameters (pH [r = 0.12, p < 0.05] and pCO2 [r = -0.17, p < 0.01]). In order to evaluate the influence of gestational age on STV values, we subdivided patients into three subgroups (< 34 weeks: n = 31; 35-37 weeks: n = 37, and > 37 wks: n = 127). Only in the subgroup < 34 wks, STV < 5.1 msec was a significant predictor of acidemia (pH < 7.0), (sensitivity: 100%, specificity: 61%, p < 0.05); in the same subgroup STV < 4.9 msec predicted pCO2 > 60 mmHg with a sensitivity: 71.4% and a specificity: 62.5% (p < 0.02). CONCLUSION: In cases < 34 weeks' gestation, STV values below 4.9 msec and 5.1 msec are able to predict umbilical artery pH < 7.0 and PCO2 > 60 mmHg, respectively.

Association between maternal-fetal Doppler velocimetry and fetal lung maturity.

AIMS: To correlate maternal-fetal Doppler velocimetry parameters to indices of fetal lung maturity (FLM). METHODS: Fifty-five consecutive third trimester pregnancies in which a pulsed-wave Doppler study, including uterine resistance index (Ut RI), umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI) and the UA/MCA ratio was performed within 24 hours before amniocentesis and within a week from birth. FLM was determined by amniotic fluid lamellar bodies count (LBs). RESULTS: A positive correlation between MCA PI and LBs (p < 0.007, r = 0.44) was found. MCA PI showed a trend to lower values in fetuses that developed RDS at birth (1.3 +/- 0.5 vs. 1.7 +/- 0.4, NS). LBs significantly decreased as Ut RI increased (O.R.: 0.98, C.I. 0.97-0.99, p < 0.05). A mean Ut RI > 0.64 was correlated to delayed FLM (LBs < 20,000/microl; sensitivity: 90.9%, specificity: 90.3%; positive predictive value: 76.9%, negative predictive value: 96.6%). COMMENT: In third trimester pregnancies abnormal uterine artery waveforms may be associated to a delayed FLM, as expressed by decreased amniotic fluid LBs.