Laura Montanari

Role of prenatal diagnosis and counseling in the management of 735 pregnancies complicated by primary human cytomegalovirus infection: A 20-year experience

BACKGROUND The burden of congenital human cytomegalovirus (HCMV) infection is well recognized. However, screening for maternal infection remains controversial in view of diagnostic challenges, counseling difficulties, and absence of medical treatment. OBJECTIVE To assess the role of prenatal diagnosis and counseling in the management of pregnancy complicated by primary HCMV infection. STUDY DESIGN Retrospective study aimed at investigating diagnostic features, options, and pregnancy outcome in 735 women with primary HCMV infection over a period of 20 years (1990-2009). RESULTS Overall, 25.6% women were found to be seronegative before the actual pregnancy. However, none were informed about HCMV infection and potential prevention strategies. Diagnosis of primary HCMV infection was achieved by seroconversion in 44.4% cases and by different combinations of virus-specific IgM, low IgG avidity, and DNAemia in 43.9% cases. Non-specific symptoms and/or haematological/biochemical alterations were recalled by 73.5% women. The onset of infection could be established, and counseling adjusted accordingly in >90% cases. The overall rate of vertical transmission was 37.1%, ranging from 5.6% for preconceptional infections to 64.1% for third trimester infections. Amniocentesis was chosen by 43.1% women, whereas pregnancy termination was requested by 15.6%. CONCLUSIONS Reference virology centers and ad hoc trained and experienced physicians are required for accurate diagnosis of primary infection in pregnancy and ensuing counseling. Prenatal diagnosis has a central role in the management of pregnancies complicated by primary HCMV infection. HCMV-seronegative women should receive adequate information.

Infant sex, obstetric risk factors, and 2-year neurodevelopmental outcome among preterm infants

Aim  To evaluate the effect of the interaction between fetal sex and obstetric variables on the risk of neurodevelopmental impairment among preterm infants.

The Impact of First-Trimester Serum Free β-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein A on the Diagnosis of Fetal Growth Restriction and Small for Gestational Age Infant

Objective: To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG). Methods: A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free β-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations. Results: The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4–3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3–6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free β-hCG were 0.21 (95% CI 0.13–0.33) and 0.26 (95% CI 0.17–0.36), respectively. Conclusion: Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.

Prognostic significance of the interaction between abnormal umbilical and middle cerebral artery Doppler velocimetry in pregnancies complicated by fetal growth restriction

Objective. To evaluate the prognostic significance of the interaction between umbilical artery (UA) and middle cerebral artery (MCA) Doppler measurements in pregnancies complicated by fetal growth restriction (FGR). Design. Cohort study. Setting. Third‐level Perinatology Center in Northern Italy. Population. A study of 184 singleton pregnancies at 24–35 weeks’ gestational age complicated by FGR and abnormal UA Doppler measurements. Methods. FGR was diagnosed by serial ultrasonograms. Neonatal brain damage was defined as the presence of cystic leukomalacia or grade III‐IV intraventricular hemorrhage. Main outcome measures. Perinatal death and neonatal brain damage. Results. The prevalence of fetal/neonatal death or brain damage was 18.2% (16/88) in pregnancies with UA absent/reversed diastolic flow and 4.2% (4/96) in those with increased UA Doppler pulsatility. Stepwise logistic regression identified decreasing gestational age (OR = 1.75, 95% confidence interval, CI = 1.35–2.22) and absent/reversed UA blood flow (OR = 3.34, 95% CI = 1.1–10.9) as predictors of fetal/neonatal death or brain damage. A MCA pulsatility index below the 10th percentile was a risk factor for fetal/neonatal death or brain damage among women with absent/reversed UA diastolic flow (14/53 as compared to 2/35; OR = 5.9, CI =1.4–40.3) but not in pregnancies with forward velocity (1/33 as compared to 3/63; OR = 0.63, 95% CI = 0.02–6.13, Synergy index = 27.7, p = 0.007). Conclusions. In pregnancies complicated by FGR and absent/reversed UA end diastolic flow, vasodilatation of the MCA is a risk factor for neonatal death or brain damage.

Interaction between risk factors for fetal growth retardation associated with abnormal umbilical artery Doppler studies

Background.  The role of antenatal risk factors associated with the occurrence of fetal growth restriction complicated by abnormal umbilical artery Doppler studies has not yet been studied extensively. We evaluated the role and the interactions of antenatal antecedents of fetal growth restriction complicated by abnormal umbilical artery end‐diastolic velocities.

Prevalence of undiagnosed autoimmune rheumatic diseases in the first trimester of pregnancy. Results of a two-steps strategy using a self-administered questionnaire and autoantibody testing

Objective  To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy.

Fetal growth and infant neurodevelopmental outcome after preterm premature rupture of membranes.

OBJECTIVE: To evaluate the prognostic values of fetal size before birth and fetal growth during the latency period in patients with preterm premature rupture of the membranes (PROM). METHODS: A prospective cohort study of 69 singleton pregnancies complicated by prolonged (14 days or more) PROM (24 to 31 weeks of gestation). Measures of fetal size and growth were compared with corresponding expected values from our reference curves. The correlations between deviations from expected measures of fetal size and growth, short-term neonatal complications, and infant neurodevelopmental outcome at 2 years were studied by univariate methods and logistic regression. RESULTS: The mean gestational ages and standard deviations at membrane rupture and at birth were 27.9 ± 2.4 and 31.5 ± 2.1 weeks. At a corrected age of 2 years, of the 65 (94.2%) survivors, 3 infants (4.6%) had cerebral palsy, 13 (20%) had minor neurodevelopmental impairment, and 49 (75.4%) were judged to have had normal development. Compared with surviving infants without a major handicap, the group of infants who died and those with cerebral palsy had lower proportions of expected birth weight (0.766 ± 0.1 as compared with 0.859 ± 0.13, P = .029), head (0.869 ± 0.07 as compared with 0.950 ± 0.07, P = .05), and abdominal (0.793 ± 0.04 as compared with 0.888 ± 0.1, P = .001) circumference growth during latency period. In logistic regression analysis, lower-than-expected ultrasound measures of fetal abdominal circumference before birth (odds ratio 1.09; 95% confidence interval 1.01, 1.18) or of abdominal circumference growth during the latency period (odds ratio 1.1; 95% confidence interval 1.01, 1.2) were significantly associated with an increased likelihood of an infant neurodevelopmental abnormality at 2-year follow-up. CONCLUSION: In pregnancies complicated by preterm PROM, lower-than-expected measures of fetal size and fetal growth were associated with an increased rate of infant neurodevelopmental outcome at 2-year follow-up. LEVEL OF EVIDENCE: II-2

Fetal erythroblast isolation up to purity from cord blood and their culture in vitro

BACKGROUND Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic investigation. We previously showed that human erythroblasts can be recovered from bone marrow and blood bank buffy coats by a physical cell separation. In the present study, we modified our previous methodology, taking into account the peculiar behavior of erythroblasts in response to modifications of pH and osmolality of the separation medium. METHODS Twenty to forty milliters of cord blood were initially centrifuged on Ficoll/diatrizoate (1.085 g/ml). The interphase cells were further separated on a continuous density gradient (1.040-1.085 g/ml). Two different gradients were initially compared: the first was iso-osmolar and neutral, whereas the second also contained an ionic strength gradient and a pH gradient (triple gradient). A subsequent monocyte depletion was performed by using magnetic microbeads coated with anti-CD14 monoclonal antibody (mAb), and erythroblasts were purified by sedimentation velocity. Purified cells were investigated by analyses with fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) and immunocytochemistry with mAb against fetal hemoglobin and were cultured in vitro. RESULTS When nucleated cells were spun on an iso-osmolar and neutral continuous density gradient, two separated bands of nucleated red blood cells (NRBCs) were obtained: a light fraction banding at 1.062 g/ml and an heavy fraction banding at 1.078 g/ml. Conversely, when cells were spun in the triple gradient, NRBCs were shifted to the low-density region. Monocyte depletion by immunomagnetic microbeads and velocity sedimentation provided a pure erythroblast population. FACS and FISH analyses and immunocytochemistry substantiated the purity of the isolated cell fraction, which was successfully cultured in vitro. CONCLUSIONS We have shown that fetal erythroblasts can be purified up to homogeneity from cord blood, but further refinements of the isolation procedure are necessary before the same results can be obtained from maternal peripheral blood.

The effect of newly diagnosed undifferentiated connective tissue disease on pregnancy outcome

OBJECTIVE The purpose of this study was to evaluate pregnancy outcome in a cohort of patients with newly diagnosed undifferentiated connective tissue disease (UCTD). STUDY DESIGN We conducted a nested case-control study that compared 41 patients who had early UCTD that was diagnosed at 11-14 weeks of pregnancy with 82 healthy control subjects. RESULTS During pregnancy, UCTD progressed to a definite connective tissue disease in 2 of 41 patients (4.9%). Sixteen of the 41 patients (39%) with UCTD tested positive for anti-Ro (SSA) antibodies. Compared with the control subjects, the women with UCTD had higher rates of small for gestational age (SGA; 12/40 vs 11/80; P = .05). The rate of complications of pregnancy (preterm delivery at </= 37 weeks of gestation, SGA, preeclampsia, late fetal loss) was 39% (16/41) among cases and 13.4% (11/82) in control subjects (adjusted odds ratio, 3.98; 95% CI, 1.59-9.49). CONCLUSION Pregnant patients with UCTD are at increased risk of SGA and complications of pregnancy.

Psychological correlates of decision-making during prenatal diagnosis: A prospective study

Abstract Objective: Decision-making during prenatal diagnosis has not been extensively studied. We aimed to determine psychological correlates and level of decisional conflict following prenatal diagnosis. Method: A total of 159 pregnant women were consecutively enrolled. All participants completed three questionnaires (the Hospital Anxiety and Depression scale, the Berlin Social Support scales and the Decisional Conflict scale) at three time points (T1 – waiting period between prenatal testing and disclosure of the results; T2 – decision phase within 3 days from test result disclosure; T3 – digestion period within 3 weeks from disclosure). Results: Women with fetal anomaly who terminate pregnancy were significantly more anxious and depressed than controls at each time point. Additionally, women with a normal fetus who terminate pregnancy presented higher level of anxiety and depression compared with controls at T2. Women who terminated pregnancy showed increased uncertainty scores at T2 and T3. Anxious and depressed individuals at T2 (decision period) were more uncertain about their choice at T3 compared to women with normal levels of anxiety and depression. Conclusion: The decision to terminate pregnancy, irrespective of test results, may determine emotional distress and psychiatric morbidity. Women who were anxious and depressed at decision appeared to be more uncertain about their choices as time passed by. A careful assessment of women during prenatal diagnosis should be useful to identify women who may benefit from psychological support.