Prenatal screening and counseling for genetic disorders

Introduction: The carriers of the same autosomal recessive disorder are usually unaware of onset of the genetic diseases in the children even if screenings are available for many of these disorders. In this paper, we report the experience of the Prenatal Diagnosis Center of AOU Federico II and we discuss the role of the screening for beta-thalassemia (BT), cystic fibrosis (CF) and for other rare genetic disorders. Materials and Methods: We analyzed retrospectively the indication for Prenatal Diagnosis (PD) of all the couples referred to our center from January 1993 to May 2013. We divided our sample into three groups: couples at high risk for BT, for CF and for other rare genetic disorders. Results: From January 1993 to May 2013, we performed 1269 PD for genetic disorders. There are still couples who discovered to be carriers of BT by screening after the birth of the affected child (n=51 (11,3%)); the majority of the people were screened for CF carrier after the birth of an affected child (n=155 (80,7%)) or through the cascade screening (n=28 (14,6%)). Large-scale screenings for rare genetic conditions are not available and people were screened only if they have a positive familial history. Conclusion: Parental screening is available for many severe and rare diseases whose genetic origin is known. The proportion of patients referred for very high-risk indications increased over time with an higher demand for rare disease. An adequate counseling is fundamental to identify women at risk for having affected child. Screening, counseling and PD of genetic diseases is a complex matter and needs for a continuous update

Maternal Body Mass Index influences Umbilical Artery Doppler Velocimetry in physiologic pregnancies.

OBJECTIVES: The aim of our study was to assess whether there is a relationship between maternal body mass index (BMI) and umbilical artery Doppler velocimetry in physiologic pregnancies. METHODS: Healthy pregnancy women, referred to our center at or before 32 weeks of gestation, were recruited. According to BMI, they were divided into underweight (BMI < 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9) and obese women (BMI ≥ 30). At 32(+0)  weeks of gestation, maternal BMI and umbilical artery Doppler velocimetry were recorded. A correlation between pulsatility index of umbilical artery and BMI was assessed by one-way ANOVA test, multiple comparison test (Bonferroni correction) and polynomial regression. RESULTS: One hundred eighty-five women were included. Mean pulsatility index of umbilical artery at 32(+0) was significantly higher in obese women (0.95 ± 0.01 vs 0.87 ± 0.01 vs 0.67 ± 0.01; p < 0.05). We found a positive correlation between Pulsatility Index of Umbilical Artery and maternal BMI (r(2)  = 0.7; p < 0.05). CONCLUSION: There is a positive correlation between BMI and pulsatility index of umbilical artery. These findings suggest that obesity has a negative effect on feto-placetal vessels. If our data will be confirmed, maternal BMI should be considered in evaluation of umbilical Doppler velocimetry

Risk of preeclampsia in of women who underwent chorionic villus sampling

OBJECTIVE: To assess the risk of preeclampsia in women who underwent chorionic villus sampling (CVS). STUDY DESIGN: This is a retrospective, single-center, cohort study. All consecutive singleton gestations who underwent chorionic villus sampling from January 2014 to January 2016 were included in the study. The primary outcome was the incidence of preeclampsia. Subgroup analysis in women with beta thalassemic trait was performed. Logistic regression, presented as adjusted odds ratio (aOR) with the 95% of confidence interval (CI), was performed. RESULTS: Five hundred forty-seven women who underwent CVS, and 1532 women who did not were analyzed. Women who underwent CVS had a significantly lower risk of preeclampsia (4.4 versus 8.0%; aOR 0.53, 95%CI 0.34-0.83), and late-onset preeclampsia (3.3 versus 6.1%; aOR 0.52, 95%CI 0.31-0.87). No statistically significant differences were found in preeclampsia with severe features, early-onset preeclampsia, and preterm birth (PTB). Women who underwent CVS due to thalassemic trait had a lower incidence of preeclampsia compare to those women who did not undergo CVS (3.3 versus 8.0%; aOR 0.39, 95%CI 0.14-0.87), while no differences were found comparing women who underwent CVS due to thalassemic trait with women who underwent CVS due to other reasons. CONCLUSIONS: Women who underwent first trimester CVS had a lower risk of preeclampsia compared to those who did not

Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis

INTRODUCTION: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide with a prevalence rate of approximately 6%. Although most cases of PPH have no identifiable risk factors, the incidence of PPH has been associated to the thromboprophylaxis in pregnancy with low molecular weight heparin (LMWH). Thus, the aim of the study is to evaluate the risk of PPH in cases of pregnant women exposed to LMWH. MATERIALS AND METHODS: Electronic research was performed in OVID, Scopus, ClinicalTrials.gov, MEDLINE, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. We included randomized controlled trials, cohort and case-control studies of women who underwent thromboprophylaxis with LMWH during pregnancy compared to a control group (either placebo or no treatment). The primary outcome was the incidence of PPH. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI). RESULTS: Eight studies including 22,162 women were analyzed. Of the 22,162 women, 1320 (6%) were administered LMWH, 20,842 (94%) women formed the nonexposed group (control group). Women treated with LMWH had a higher risk of PPH (RR 1.45, 95%CI 1.02-2.05) compared to controls; there was no difference in mean of blood loss at delivery (MD -32.90, 95%CI 68.72-2.93) and in risk of blood transfusion at delivery (RR 1.24, 95%CI 0.62-2.51), respectively. CONCLUSIONS: Women who receive LMWH during pregnancy have a significantly higher risk of developing PPH. Women who receive LMWH during pregnancy have neither significantly higher mean blood loss at delivery nor higher risk of blood transfusion

Diagnostic accuracy of intracranial translucency in detecting spina bifida: a systematic review and meta-analysis

OBJECTIVE: To evaluate the diagnostic accuracy of intracranial translucency (IT) in the detection of spina bifida (SB) in the first trimester of pregnancy. METHODS: We included study assessing the accuracy of sonographic measurements of IT in a mid-sagittal view of the fetal face in prediction of SB in the first trimester of pregnancy. The primary outcome was the accuracy of IT in prediction of spina bifida. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR), and diagnostic odds ratio for the overall predictive accuracy of IT were computed. RESULTS: Nine studies (21 070 fetuses) were included in the analysis. IT was successfully assessed in the majority of fetuses 97.8% (95% CI 97.6-98.0). The diagnostic performance of IT in detecting SB was as follows: sensitivity: 53.5% (95% CI 42.4-64.3), specificity: 99.7% (95% CI 99.6-99.8), positive LR: 62.1 (95% CI 12.2-317), negative LR:0.55 (95% CI 0.45-0.68), and diagnostic odds ratio: 223 (95% CI 25-2039). CONCLUSIONS: Intracranial translucency had low diagnostic accuracy in prediction of open spina bifida, thus questioning its role as a screening marker for open SB in an unselected population. When looking at the individual study data, it appears that IT assessment for open SB prediction can be affected by a high rate of false positive results potentially leading to unnecessary parental anxiet

GRK2 Levels in Umbilical Arteries of Pregnancies Complicated by Gestational Hypertension and Preeclampsia

BACKGROUND G-Protein coupled receptor kinase 2 (GRK2) represents a regulator of cell function in different cardiovascular conditions, including high blood pressure. The relationship between elevated GRK2 levels and impaired vasorelaxant responses is causative of hypertension through the increase in vascular resistances. The aim of this study is to ascertain if this feature is present in the fetal placental vasculature of pregnancies complicated by hypertensive disorders. METHODS We have assessed GRK2 levels in the umbilical arteries (UA) of 21 preeclamptic or gestational hypertensive and 23 normotensive women at time of delivery. RESULTS GRK2 levels were increased in the hypertensive group (0.83 +/- 0.14 vs. 0.48 +/- 0.06 densitometry units; P < 0.05). GRK2 levels were in correlation and in linear regression with systolic, diastolic, and mean arterial pressure (P < 0.05, r(2) = 0.12, r(2) = 0.11, r(2) = 0.12). Correlations did not reach a significant value for other clinical parameters such as gestational age at birth, umbilical artery pulsatility index, maternal proteinuria, and neonatal birth weight. Out of the 21 hypertensive women, 7 who developed a preeclampsia associated with early preterm delivery (before 34 weeks) had a significantly lower GRK2 levels compared to the remaining 14 (0.51 +/- 0.12 vs. 1.08 +/- 0.20 densitometry units, P < 0.05). CONCLUSIONS We conclude that elevated GRK2 levels in the umbilical vasculature is correlated to elevated blood pressure levels, with a likely compensatory rather than causative role since the lack of protective effect of elevated GRK2 levels may negatively affect the outcome of the hypertensive state

Fetal heart rate monitoring and neonatal outcome in a population of early- and late-onset intrauterine growth restriction

AIM: The early-onset intrauterine growth restriction (IUGR) is associated with severe placental insufficiency and Doppler abnormalities. The late-onset IUGR is associated with mild placental insufficiency and normal Doppler velocimetry. The computerized cardiotocographic (cCTG) monitoring is used to evaluate the fetal well-being in pregnancies complicated by IUGR. Our aim was to investigate the cardiotocographic characteristics of IUGR fetuses and to identify every cCTG difference between Healthy and IUGR fetuses. METHODS: Four hundred thirty pregnant women were enrolled starting from the 28th week of gestation until the time of delivery: 200 healthy and 230 IUGR fetuses. Fetal heart rate (FHR) baseline (FHR), short-term variability (STV), long-term irregularity (LTI), delta, interval index (II), approximate entropy (ApEn), high frequency (HF), low frequency (LF), movement frequency (MF), LF/(HF + MF) ratio (LF/(HF + MF)) and number of decelerations were examined. Newborn baby data were also collected. RESULTS: The parameters of short- and medium-term variability discriminate between IUGR and healthy fetuses before 36 weeks including FHR, STV, LTI and delta discriminate between each subgroup of IUGR were compared to each one of the other two (P < 0.05). CONCLUSION: cCTG is a useful tool for the evaluation of chronic hypoxemia, which causes a delay in the maturation of all components of the autonomic and central nervous system. However, cCTG requires integration with fetal ultrasound and Doppler vessels evaluation to improve the ability to predict the neonatal outcome

Screening for cervical carcinoma in HIV-infected women: Analysis of main risk factors for cervical cytologic abnormalities

AIM: The aim of this study was to identify potential predictive factors for cervical disease in women with HIV and to evaluate adherence during follow-up to cervical cancer screening. METHODS: In order to identify the independent role of factors associated with the presence of a cervical abnormality, all of the variables showing in univariate analyses a potential association with the outcome variable (presence of cervical abnormalities) were entered into a multivariate logistic regression model, along with age at first visit to our center, and age at diagnosis. RESULTS: A total of 540 HIV-positive women who received screening for cervical cancer during the first year after their first visit to our center were included in the analysis; 423 (78.3%) had normal cytology and 117 (21.7%) had cytological abnormalities, classified as follows: 21 atypical squamous cells of undetermined significance (17.9%); 51 low-grade squamous intraepithelial lesions (43.6%); 41 high-grade squamous intraepithelial lesions (35.0%); and four cervical cancers (3.4%). In our study, women with more than two previous pregnancies were significantly associated with a lower risk of cervical cytological abnormalities compared to the other women. Women with CD4+ levels of 200-499/mm3 had a higher risk of developing cervical cytological abnormalities compared to those with a CD4+ level > 500/ mm3 . CONCLUSION: In summary, management of HIV-positive women must be modeled on HIV-clinical status, CD4+ cell count, drug regimen, and adherence to follow-up, relying on the cooperation of highly qualified professionals. In HIV-positive women, an adequate screening and follow-up allows for a reduced occurrence of advanced cervical disease and prevents recourse to invalidating surgical interventions

Incidence of toxoplasmosis in pregnancy in Campania: A population-based study on screening, treatment, and outcome

INTRODUCTION: The aim of this study was to evaluate the incidence of toxoplasmosis infection during pregnancy and to describe the characteristics of the serological status, management, follow-up and treatment. MATERIAL AND METHODS: This is a population-based cohort study of women referred for suspected toxoplasmosis during pregnancy from January, 2001 to December, 2012. Suspected toxoplasmosis was defined as positive IgM antibody during pregnancy. Women with suspected toxoplasmosis during pregnancy were classified into three groups: seroconversion, suspected infection, or no infection in pregnancy. Women in the first and second group were treated according to local protocol, and amniocentesis with toxoplasmosis PCR detection and serial detailed ultrasound scans were offered. Neonates were investigated for congenital toxoplasmosis at birth and were monitored for at least one year after birth. RESULTS: During the study period, there were 738,588 deliveries in Campania. Of them 1159 (0.2%) were referred to our Institution for suspected toxoplasmosis during pregnancy: 183 (15.8%) women were classified as seroconversion, 381 (32.9%) were suspected infection, and 595 (51.3%) were not infected in pregnancy. Neonatal outcome was available for 476 pregnancies, including 479 neonates (3 twins, 473 singletons), out of the 564 pregnancies with seroconversion or suspected infection. 384 (80.2%) babies were not infected at birth and at follow-up, 67 (14.0%) had congenital toxoplasmosis, 10 (2.1%) were voluntary induced termination of pregnancy, 15 (3.1%) were spontaneous miscarriage, and 4 (0.8%) were stillbirth (of which one counted already in the infected cohort). Considering cases of congenital toxoplasmosis, the transmission rate in women with seroconversion was 32.9% (52/158), and in women with suspected infection was 4.7% (15/321). CONCLUSIONS: Toxoplasmosis is uncommon in pregnancy with overall incidence of seroconversion and suspected infection in pregnancy of 0.8 per 1000 live births and incidence of congenital toxoplasmosis 0.1 per 1000 live births when applying a strict protocol of screening, follow-up, and treatment. 51.3% (595/1159) of women referred to our center for suspected infection were actually considered not infected