The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. OBJECTIVES: We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. METHODS: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole. RESULTS: Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. CONCLUSIONS: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.

Cardiovascular Effects of a Thoracoamniotic Shunt in a Fetus Affected by Isolated Right Congenital Diaphragmatic Hernia and Hydrops.

A thoracoamniotic shunt was placed in a fetus affected by a right congenital diaphragmatic hernia (RCDH) complicated by voluminous nonimmune hydrops (NIH) at 30 weeks of gestation. The fetus showed congestive cardiac failure with a combined cardiac output (CCO) of 460.7 ml/min (Z-score: -1.2). After seven days, no edema, ascites, or pleural effusion was present. CCO increased significantly, reaching a Z-score of -0.2, as well as right and left cardiac output (Z-scores: -0.3 and -0.8, respectively). Two weeks later, the cardiac function and the ascites got worse despite the correct shunt placement, suggesting a possible occlusion. At 33 weeks, a C-section was performed due to labor in breech presentation. Despite the intensive care provided, the newborn died due to pulmonary hypertension and respiratory insufficiency. The thoracoamniotic shunt's effect on fetal circulation and the mechanisms of NIH in the event of RCDH are still unclear. Due to the high mortality rate of this condition and its poorer outcomes compared to left-sided defects, shunting cannot be considered an efficient attempt to improve fetal and neonatal survival rates to date. A close relationship between the amount of lymphatic effacement and cardiac function is clear, but further studies are needed to provide more information about this severe condition and its treatment.

Ductus Venosus Agenesis in Monochorionic Twin Pregnancies Complicated by Fetal Growth Restriction: When to Deliver?

Introduction: The prevalence of ductus venosus agenesis (ADV) in singleton pregnancies ranges from 0.04% to 0.15%, while its prevalence in twins remains largely unknown. To our knowledge, in the literature, there is only a single case report of a monochorionic diamniotic (MCDA) pregnancy complicated by ADV. Fetuses with ADV are at increased risk for congenital cardiac disease, heart failure, and fetal growth restriction (FGR). Consequently, these pregnancies have a heightened risk of experiencing an adverse outcome, like stillbirth and neonatal or infant death. Closer antenatal monitoring is warranted when ADV is suspected. Currently, there are no guidelines regarding the standard of care in cases of ADV and no recommendations for the timing of delivery in either singleton or twin pregnancies. Cases: This study aims to provide a comprehensive overview of the management of twin pregnancies complicated by ADV, featuring two cases of MC twins with concurrent sFGR and ADV in one twin. Discussion: These pregnancies experienced completely different outcomes, underscoring the necessity for personalized management tailored to the specific risk factors present in each pregnancy. Typically, in MCDA pregnancies with severe sFGR (type II and III), delivery represents the most reasonable option when venous Doppler abnormalities are identified. However, the absence of the DV complicates the management and the process of decision-making regarding the timing of delivery in cases of sFGR and ADV. We emphasize that effective decision-making should be guided by the presence of additional risk factors, including velamentous insertion, significant estimated fetal weight discordance, and progressive deterioration of the Doppler over time. Conclusions: Our experience suggests that these factors are strongly correlated with poorer outcomes. Given this context, could it be acceptable, in the case of MC pregnancy complicated by severe sFGR and ADV, with worsening findings and additional risk factors (e.g., velamentous insertion, severe birth weight discrepancy), to anticipate the time of delivery starting from 30 weeks of gestational age?

Is the mental health of couples with twins more at risk? Results from an Italian cohort study.

Introduction: Our retrospective study aimed to investigate whether parents of twins encounter heightened psychological and emotional distress one year after childbirth, in comparison to parents of singletons within an Italian cohort. Methods: Exclusion criteria included multiparity, preterm birth, congenital anomalies, stillbirth, >2 fetus pregnancies, and pre-existing maternal mental health disorders. Out of the 300 couples (600 parents) invited to participate, 286 parents (158 mothers, 128 fathers) successfully completed a self-administered survey. We analyzed three scores separately for mothers and fathers, differentiating between singleton and twin pregnancies: the Edinburgh Postnatal Depression Scale (EPDS) score, the State and Trait Anxiety Inventory (STAI)-Y1 score, and the STAI-Y2 score. Results: Logistic models were used to assess the influence of age, BMI, marital status, education, and employment on the three binary scores (EPDS, STAI-Y1, and STAI-Y2), revealing no significant differences in absolute scores between parents of singletons and twins. Paired analysis revealed significantly higher EPDS (mean increase: 3.8, SD: 6.5), STAI-Y1 (mean increase: 5.4, SD: 12.5), and STAI-Y2 (mean increase: 4.5, SD: 12.4) scores for mothers (p < 0.0001). Approximately 10% of women and 8% of men reported suicidal thoughts. Discussion: Contrary to expectations, no substantial psychological differences emerged between parents of twins and singletons. Adjusting for confounders through univariate analysis maintained nonsignificant trends. Nevertheless, caution in interpretation is warranted due to strict inclusion criteria favoring twin pregnancies with better outcomes. Unintended bias could have resulted from routine psychological support offered to mothers of twins in our clinic. This presents an important framework for future research, including randomized controlled trials comparing parents of multiples with psychological support to those without.Finally, the elevated prevalence of depression symptoms and suicidal thoughts in our cohort underscores the importance of mental health during pregnancy and early parenting. We advocate for the screening of parents for postpartum depression and various psychological conditions, encompassing a spectrum of anxiety disorders. Those at elevated risk of mental distress should be proactively offered appropriate support.

A rare case of renal dysplasia: prenatal and postnatal management.

The ultrasonographic detection of renal anomalies may modify obstetric management and facilitate pediatric care of the newborn. We performed prenatal differential diagnosis of an isolated unilateral cystic renal mass (71 × 74 × 82 mm) in a pregnant woman at 26 weeks of gestation. No other abnormalities were detected by ultrasonography, except for polyhydramnios. Repeated percutaneous cyst aspirations were required because of the increasing risk of vital organ damage. Postnatal nephroureterectomy was performed. Anatomopathologic analysis led to the diagnosis of segmental renal dysplasia, which could not be included in any of the four groups of Potter's classification of cystic renal dysplasia.

The impact of placental anastomoses and umbilical cord insertions' sites on monochorionic twin pregnancy outcomes: Evidence from color-dye injection studies.

INTRODUCTION: Our knowledge of monochorionic pregnancies' complications is largely based on the extensive ongoing research on monochorionic placental structure. Previous studies on the concordance of umbilical cord insertions are limited. This study aimed to evaluate placental anastomoses and cord insertions as independent risk factors for neonatal adverse outcomes. METHODS: This was a prospective study conducted at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy from April 2021 to December 2022. Seventy-six women with a monochorionic pregnancy were enrolled at their first-trimester scan. After delivery, all placentas that were confirmed to be monochorionic were analyzed according to standard protocols, including those of complicated monochorionic twin pregnancies. The primary outcomes were a Composite Monochorionic Pregnancy Outcome (CMPO) and a Composite Neonatal Adverse Outcome (CNAO). The secondary outcome was the birth weight discordance between the neonates. RESULTS: The CMPO occurred in 15.8 % pregnancies, and the CNAO occurred in 67.1 % pregnancies. The analysis confirmed a significant association between velamentous cord insertions and neonatal adverse events (p = 0.003). Also, a significant positive association (p = 0.0326) between twin birth weight discordance and discordance in twins umbilical cord insertions' sites was found. No significant association between the number and type of the anastomoses and both the CMPO or CNAO was detected. DISCUSSION: Our data suggest that the routine sonographic assessment of umbilical cords' insertion sites during the first trimester could be helpful in predicting fetal and neonatal adverse events. We believe that this sonographic assessment should start to be implemented in our routine care of monochorionic pregnancies.

Ultrasonographic evidence of persistent hyperextension of the fetal neck: is it a true sign? A diagnostic and prognostic challenge.

OBJECTIVE: The purpose of this study was to evaluate the clinical evolution, structural anomalies associated and neonatal outcomes of fetal neck hyperextension in two cases with prenatal ultrasound diagnosis in two different gestational ages. METHODS: In 2019, two cases of fetal hyperextension came to our attention. Follow-up information was obtained from hospital medical records and obstetrical care providers. RESULTS: Two woman were investigated in our institution for the presence of fetal abnormalities in the II and III trimester, respectively. In both cases, fetal attitude presented persistent fetal neck hyperextension. One of the two fetuses had a mild ventriculomegaly and suspected for micrognathia. Both had an amniotic fluid increase. One of two had no movement in the lower and upper limbs in ultrasound scans associated with club foot and suspected scoliosis. Both were born by cesarean section with pretty different prognosis: one healthy baby had a retarded psychomotor development and the other one died after 6 months. A precise diagnosis was possible only in one case. CONCLUSION: The early identification of a fetus with persistent hyperextension of the fetal head should require a detailed ultrasound exam for structural abnormalities and a careful prenatal counseling due to possible postnatal outcome.

Expression of RIZ1 protein (Retinoblastoma-interacting zinc-finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2.

The nuclear protein methyl-transferase Retinoblastoma-interacting zinc-finger protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in target tissues. Silencing of RIZ1 expression is common in many tumors. We analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in cultured prostate epithelial cells (PEC). Moreover, we studied the possible involvement of RIZ1 in estrogen action on the EPN prostate cell line, constitutively expressing both estrogen receptor (ER)-alpha and beta. RIZ1 protein, found in the nucleus of normal PECs by immunohistochemistry, was progressively lost in cancer tissues as the Gleason score increased and was only detected in the cytoplasmic compartment. RIZ1 transcript levels, as assayed by semi-quantitative RT-PCR in primary PEC cultures, were significantly reduced in cancer cells (P < 0.05). In EPN DHT treatment significantly increased RIZ1 transcript and protein levels (P < 0.05); E2 induced a reduction of S phase without significant changes of RIZ1 expression. In E2-treated EPN cell extracts RIZ co-immunoprecipitated with ERbeta and ERalpha. Our data demonstrate that RIZ1 is expressed in normal PECs and down-regulated in cancer cells, with a switch of its sub-cellular localization from the nucleus to the cytoplasm upon cancer grade progression. RIZ1 expression levels in the PECs were modulated by DHT or E2 treatment in vitro. Furthermore, the E2 effects on ER-expressing prostate cells involve RIZ1, which confirms a possible role for ER-mediated pathways in a non-classic E(2)-target tissue.

Paternal exposure and counselling: experience of a Teratology Information Service.

We describe paternal exposure and counselling in a selected population calling to an Italian Teratology Information Service (TIS). The majority of callers asked for paternal drug exposure (76%, drugs except chemotherapy) and treatment for cancer (17%, chemotherapy and/or radiotherapy). Others asked for exposure to diagnostic radiations (4%), recreational drugs (2%) and occupational chemicals (1%). Among paternal drugs neurological compounds, immunosuppressive drugs and antiviral agents were the main reasons for calling. In humans, there are no evidences of birth defects after paternal exposures, but to minimize any possible risk, counselling in men exposed to radio and chemotherapy should recommend delaying conception for at least 3 months after the end of the therapy. Male patients treated with drugs, whose teratogenic potential has been well assessed or suspected for maternal exposure, should be advised to practice effective birth control during therapy and up to one or two cycles of spermatogenesis and to avoid semen contact with vaginal walls during first trimester of pregnancy.

Glaucoma Drug Therapy in Pregnancy: Literature Review and Teratology Information Service (TIS) Case Series.

BACKGROUND: There are many contradictions about pregnancy and fetal/neonatal outcomes after topical use of timolol alone or timolol in combination with other antiglaucoma medications. METHODS: Seventy-five pregnant women exposed to antiglaucoma medications were followed prospectively by phone interviews. 27 women used timolol as monotherapy, 48 women used timolol as a part of multidrug therapy. We selected a control group of 187 healthy pregnant women. RESULTS: Topical use of timolol alone or timolol in combination with other antiglaucoma medications does not influence pregnancy or fetal/neonatal outcomes. CONCLUSION: Beta-blocker is the first choice treatment for glaucoma in pregnancy but, when necessary, multidrug therapy should not to be excluded.

Prenatal detection of megacystis: not always an adverse prognostic factor. Experience in 25 consecutive cases in a tertiary referral center, with complete neonatal outcome and follow-up.

INTRODUCTION: Megacystis is a condition of abnormal enlarged fetal bladder for gestational age, which is usually associated with urological malformations that may constitute a life-threatening condition for the baby. OBJECTIVE: The purpose of this study was to assess the prognostic and etiological criteria of fetal megacystis and to describe the neonatal outcome in a large series collected in a single tertiary center. STUDY DESIGN: A retrospective observational study was conducted between 2008 and 2012. We reviewed all consecutive cases of fetal megacystis diagnosed during routine ultrasound (US) screening. The following data were collected and analyzed: maternal age, gestational age at diagnosis, prenatal ultrasonographic details of the urinary system, extra-urinary ultrasonographic anomalies, fetal karyotype, pregnancy outcome, postnatal diagnosis, and medical/surgical follow-up. RESULTS: Of the 25 fetuses included in this study, 76% were males. The mean gestational age (GA) at diagnosis was 23.1 ± 7.5 weeks (range 12-34), among them only four (16%) were diagnosed during the first trimester. Associated urological malformations were detected in 92% (n = 23) of the cases, while other malformations were detected in 36% (n = 9). Oligohydramnios or anyhydramnios were observed in 52% (n = 13) of the cases. Twelve (48%) fetuses were considered as having poor prognosis for renal function. Vesicocentesis with or without vesico-amniotic infusion were performed in 28% (n = 7) of the cases. Pregnancy outcome was surprisingly good, with only one case of prenatal death and survival rate of 96% (n = 24) of liveborn babies. Posterior urethral valve (PUV) (n = 9, 36%) was the most common etiology of the fetal megacystis, followed by persistent urogenital sinus (n = 2, 8%), Prune belly syndrome (n = 2, 8%) and bilateral vescico-ureteral reflux (VUR) (n = 2, 8%). Surgical or endoscopic procedures were performed in 75% (n = 18) of the cases. Six (24%) newborns presented with moderate/severe respiratory distress that requested invasive assisted ventilation. Three cases (n = 3, 12%) of perinatal death were observed due to severe impaired renal function. After a median follow-up of 29 months renal function was good in 79% (n = 19) of the cases. CONCLUSIONS: Fetal megacystis may underline a wide range of associated pathologies with the highest prevalence of urinary malformation. Optimal counseling of the involved parents requires a multidisciplinary approach to allow the best management during the pregnancy and the perinatal period. Despite the high risk of renal failure, lung hypoplasia, and severe associated anomalies, the outcome of fetuses with megacystis could be improved thanks to an appropriate perinatal diagnosis and neonatal management.

Invasive fetal therapies: approach and results in treating fetal ovarian cysts.

OBJECTIVE: To show the validity of prenatal invasive surgical intervention when a fetal ovarian cyst is diagnosed, compared to a wait and see attitude, in order to avoid possible prenatal and postnatal complications. PATIENTS: Fourteen cases of intra-abdominal cysts monitored in our center between April 2005 and November 2010. All cases were first diagnosed in the third trimester, and were monitored for the remainder of the pregnancy and after delivery (2 months-3 years postnatally). SURGICAL INTERVENTION: Upon maternal and fetal cutaneous anesthesia performed trans-amniotically, the cystic fluid (mean contents 43.85 cc, DS 46.27) was extracted for cytological, biochemical, and hormonal examination. RESULTS: Thirteen cases of intra-abdominal cysts (92.8%) were fetal ovarian cysts. Ninety-two percent of pregnancies bearing such a condition were successfully concluded (n = 12). Sixty-nine percent concluded in vaginal delivery (n = 9). None experienced maternal and/or fetal complications. Every drained cyst had an estradiol concentration higher than 10,000 pg/ml. CONCLUSIONS: The aspiration of ovarian cysts exceeding a 40 mm diameter, performed as early as possible, allows a good longitudinal treatment of this fetal affection, thus avoiding torsion, tissue necrosis, and invasive postnatal surgery, as well as giving hope of future gestational capability to the fetus/newborn.

Sexuality, pre-conception counseling and urological management of pregnancy for young women with spina bifida.

A great number of newborns with spina bifida now survive with a growing life expectancy. Support with regard to sexual issues is essential in the management of adolescents with spina bifida, who require specific knowledge of sexual problems related to their disability. Women with spina bifida are usually fertile and need pre-conception counseling. Furthermore, compared to healthy women they have a higher chance of conceiving a child with spina bifida, so they are treated with periconceptional folic acid supplements. In addition pregnancies in women with spina bifida require adequate management of secondary conditions, mainly urological issues, which are exacerbated during pregnancy. This article gives an overview of sexual education, sex functioning and sexual activity among adolescents with spina bifida. Moreover, we aim to support young women with spina bifida, providing pre-conception counseling and practical guidelines essential for the urological management of their pregnancy.

Antiepileptic drugs during pregnancy: pharmacokinetics and transplacental transfer.

Epilepsy represents the most common maternal neurological disorder requiring continuous treatment during pregnancy. Maintaining optimum seizure control is an important objective in pregnancy, and the majority of women with epilepsy will need to continue antiepileptic drugs (AEDs). AEDs are frequently used to treat several other conditions, such as headaches and mood disorders. They have been associated with an increased risk of congenital malformations, minor anomalies, congenital syndrome and development disorders. This risk seems to be higher among women using polypharmacy and valproic acid. Neural tube defects are associated with valproic acid and carbamazepine exposure. New AEDs seem to have a less teratogenic effect, but human experience is still limited. The purpose of this review is to provide an update on AED exposure in pregnancy, focusing on pharmacokinetics and transplacental transport.

Use of the Internet by women seeking information about potentially teratogenic agents.

OBJECTIVE: The aim of this study was to evaluate if the Internet provides evidence-based information to women seeking information about teratogenic risk factors and women's risk perception. Furthermore, we evaluated the possible risk related to teratogen exposure in the study sample and analysed age, gravidity, educational level, geographic location, marital status and type of exposure compared to a control group made up of women who did not use the Internet to search for teratogen-related information. STUDY DESIGN: Between October 2008 and June 2009, a questionnaire was administered to pregnant women calling our Teratology Information Service concerning a suspected teratogenic exposure. RESULTS: Fifty-seven percent (n=116) of callers had used the Internet to find medical information about their exposure, while 43% (n=87) had not. Internet users had a medium-high level of education and consulted the Internet because of its convenience, usually early in their pregnancy. We verified the accuracy of the information the women obtained from the Internet and found that 59.5% (n=69) of women received evidence-based answers; 18.1% (n=21) were informed that their exposure was dangerous when it was not; 4.3% (n=5) were wrongly reassured; and the rest (n=18) were not able to interpret the data they found or found no relevant information. CONCLUSIONS: Internet use during pregnancy is a widespread phenomenon as the Internet offers the opportunity to share apprehensions and doubts with other women, but it can often lead to increased and unjustified anxiety. Medical information published on websites cannot be considered a substitute for informed medical advice, and patients should not take any action before consulting with a health care professional.