"Residential greenness, gestational diabetes mellitus (GDM) and microbiome diversity during pregnancy".

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. METHODS: Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24-28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. RESULTS: Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300 m buffer had lower odds of GDM (OR = 0.45, 95% CI: 0.16, 1.26, p = 0.13) and decreased change in mean glucose levels (ß = -6.28, 95% CI: 14.91, 2.24, p = 0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500 m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. CONCLUSION: Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations.

Revised Protocol for Secondary Prevention of Congenital Cytomegalovirus Infection With Valaciclovir Following Infection in Early Pregnancy.

BACKGROUND: A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol. METHODS: All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study. RESULTS: Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02). CONCLUSIONS: This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

The association between maternal cytomegalovirus urinary excretion and congenital infection rate.

BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy. METHODS: This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102. FINDINGS: Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09-0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported. INTERPRETATION: Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus. FUNDING: None.

Women's preferences for mode of second birth-A prospective study of two Israeli birth cohorts.

INTRODUCTION: Various biopsychosocial factors affect women's preferences with respect to mode of birth, but they are usually not examined simultaneously and prospectively. In the current study, we assessed the contribution of personal characteristics of first-time mothers, their prior prenatal perceptions, events during birth, and subjective birth experiences, on their preference about mode of second birth. METHODS: This was a secondary analysis of two prospective birth cohort studies. Participants included 832 primiparous women recruited mostly from women's health centers in Israel, and through natural birth communities and cesarean birth websites. Women completed questionnaires prenatally and were followed up at 6-8 weeks postpartum to understand their preferences for a second birth. RESULTS: Regression models indicated that after vaginal first birth, being less religious, believing that birth is a medical process, and having a negative experience increased the odds of preferring primary cesarean for the second birth. After cesarean birth, being more religious, having higher education, conceiving spontaneously, having a more negative birth experience, and perceiving better treatment from the staff during birth contributed to preferring vaginal birth for the second birth. CONCLUSIONS: Religiosity is central to women's preferences, probably because of its association with the desire to have many children. Modifiable factors, such as women's beliefs about the nature of birth, their overall birth experience, and their perceived treatment from the staff, could influence the uptake of having vaginal births. Intrapartum care that is empathic and encouraging, along with education about modes of birth, could help decrease cesarean birth rates.

Second Trimester Biochemical Markers as Possible Predictors of Pathological Placentation: A Retrospective Case-Control Study.

OBJECTIVE: We aimed to evaluate the association between second trimester biochemical markers and pathological placentation. METHODS: This was a retrospective case-control study (2007-2014) of singleton gestations at a university-affiliated tertiary center. Women with pathologic placentation were subdivided into three groups: placenta accreta (group A), placenta previa (group B), or both (group C). We compared second trimester biochemical screening markers taken between 16 + 0 and 19 + 6 weeks of gestation between groups A, B, and C, and women with normal placentation (group D). Obstetrical and neonatal outcomes, risk factors for pathologic placentation, and second trimester biochemical marker values were compared between groups. RESULTS: Overall, 301 deliveries were evaluated: 64 (21%) in group A, 66 (22%) in group B, 17 (6%) in group C, and 153 (51%) in group D. Each of the pathological placentation groups individually had a higher median alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) multiples of median (MoM) than the controls, with the highest values of AFP and hCG observed among women with placenta accreta and the lowest values among the controls. When a multivariant analysis was applied, the hCG levels remained significantly correlated with pathological placentation. Receiver operation characteristic curves for AFP, hCG, or both were computed. For AFP the area under the ROC curve (AUC) was 0.573 (95% CI 0.515-0.630, p < 0.0274) and a cut-off value above 0.99 MoM demonstrated a sensitivity and specificity of 71 and 46%, respectively, for the prediction of pathological placentation. For hCG, the AUC was 0.662 (95% CI 0.605-0.715, p < 0.0001) and a cut-off value of 1.25 MoM demonstrated a sensitivity and specificity of 53 and 68%. When both markers were plotted, the AUC was 0.668 (95% CI 0.611-0.721, p < 0.0001) and sensitivity and specificity were 63 and 64%, respectively. A percentile MoM cut-off approach distinguished between two groups: a high-risk group (patients with AFP or hCG or both above the 75th percentile, odds ratio (OR) for pathological placentation 2.27, 95% CI 1.42-3.63), and a low-risk group (patients with AFP or hCG or both below the 25th percentile, OR for pathological placentation 0.38, 95% CI 0.24-0.60). CONCLUSION: Second trimester biomarkers such as hCG and AFP can be used to raise a suspicion towards characterizing women into high-risk and low-risk groups for pathological placentation.

Hematologic Adverse Events Associated With Prolonged Valganciclovir Treatment in Congenital Cytomegalovirus Infection.

BACKGROUND: Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d. METHODS: A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected. RESULTS: One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded. CONCLUSIONS: Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.

Changes in the basic birth beliefs following the first birth experience: Self-fulfilling prophecies?

Women's basic beliefs about birth as a natural and as a medical process are associated with childbirth choices and experience. These beliefs have only recently been quantified and not much is known about their development. In the current study, we assessed the differential effects of the objective and the subjective birth experience on changes in these beliefs. Using self-report questionnaires, we evaluated prenatal to postpartum changes among 342 Israeli first-time mothers. Participants were recruited during pregnancy, between February 2016 and January 2017, mostly in clinical settings, and followed-up two months postpartum. On average, women's beliefs about birth being natural weakened following childbirth and their belief about birth being medical strengthened. In regression models, it was either the objective or the subjective experience that was related to change in the basic birth beliefs: A more medicalized birth was associated with strengthening of the medical belief while greater birth satisfaction was related to strengthening of the natural belief. A mediation effect was observed, which indicated that the beliefs are strengthened when the lived experience fulfilled women's expectation about birth being satisfying, natural or medical. This study adds to the growing body of knowledge regarding the development and evolution of the birth beliefs. It highlights the need to view the beliefs separately and to distinctively assess the objective and subjective birth experience. It supports the need to empower mothers, especially those who had more medicalized births or unsatisfactory ones, which would help conserve their belief in their body and in the normal physiological course of birth.

Testing a biopsychosocial model of the basic birth beliefs.

BACKGROUND: Women perceive what birth is even before they are pregnant for the first time. Part of this conceptualization is the basic belief about birth as a medical and natural process. These two separate beliefs are pivotal in the decision-making process about labor and birth. Adapting Engel's biopsychosocial framework, we explored the importance of a wide range of factors which may contribute to these beliefs among first-time mothers. METHOD: This observational study included 413 primiparae ≥24 weeks' gestation, recruited in medical centers and in natural birth communities in Israel. The women completed a questionnaire which included the Birth Beliefs Scale and a variety of biopsychosocial characteristics such as obstetric history, birth environment, optimism, health-related anxiety, and maternal expectations. RESULTS: Psychological dispositions were more related to the birth beliefs than the social or biomedical factors. Sociodemographic characteristics and birth environment were only marginally related to the birth beliefs. The basic belief that birth is a natural process was positively related to optimism and to conceiving spontaneously. Beliefs that birth is a medical process were related to pessimism, health-related anxiety, and to expectations that an infant's behavior reflects mothering. Expectations about motherhood as being naturally fulfilling were positively related to both beliefs. CONCLUSION: Psychological factors seem to be most influential in the conceptualization of the beliefs. It is important to recognize how women interpret the messages they receive about birth which, together with their obstetric experience, shape their beliefs. Future studies are recommended to understand the evolution of these beliefs, especially within diverse cultures.

Congenital Cytomegalovirus Infection After a Multiple Birth Pregnancy.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is an important cause of hearing loss and neurodevelopment delay. While data on vertical transmission and neonatal outcome after singleton pregnancy with cCMV are well established, only scarce reports have addressed cCMV in multiple birth pregnancies. Furthermore, no studies have yet compared the outcome after birth and long-term follow-up of children with cCMV born after a singleton versus multiple pregnancies. METHODS: Infant outcome after birth of symptomatic versus asymptomatic infection was compared for infants born with cCMV after multiple (study group) and singleton (control group) pregnancies in a 1:2 ratio. RESULTS: Of 508 infants diagnosed with cCMV, 25 (4.9%) were born after a multiple pregnancy. Children in the study and control groups did not differ in terms of specific prenatal CMV investigations including amniocentesis and brain magnetic resonance imaging studies. However, prematurity rates were significantly higher in the study compared with control group (52% vs. 4%, P < 0.001). There was a higher rate of symptomatic cCMV infection in the study group than in the controls (48% vs. 14%, P < 0.001). Hearing impairment at birth was also more frequent in the study group (32% vs. 8%, P = 0.016). A long-term follow-up demonstrated that children in the study group had higher rates of neurologic sequelae (hearing impairment or neurodevelopmental delay) compared with children in the control group (20% vs. 4%, P = 0.016). CONCLUSIONS: Infants with cCMV born after multiple birth pregnancies are born earlier and have a higher risk of symptomatic disease at birth and worse long-term neurologic outcome than those born after a singleton pregnancy. This important group of children warrants meticulous prenatal and postnatal care.

Symptomatic congenital cytomegalovirus disease following non-primary maternal infection: a retrospective cohort study.

BACKGROUND: Scarce data exist about screening, diagnosis and prognosis of non-primary Cytomegalovirus (CMV) during pregnancy. We aimed to examine antenatal diagnosis of maternal non-primary CMV infection and to identify risk factors for congenial CMV disease. METHODS: Retrospective cohort of 107 neonates with congenital symptomatic CMV infection, following either primary (n = 95) or non-primary (n = 12) maternal CMV infection. We compared the groups for the manifestations and severity of congenial CMV disease, as well as for possible factors associated with the risk of developing CMV related infant morbidity. RESULTS: Disease severity is not similar in affected newborns, with a higher incidence of abnormal brain sonographic findings, following primary versus non-primary maternal CMV infection (76.8% vs. 8.3%, p < .001). Symptomatic congenital CMV disease following a non-primary infection is more frequent if gestational hypertensive disorders and/or gestational diabetes mellitus have ensued during pregnancy (33.3% vs. 9.9%, p <0.038), as well as if any medications were taken throughout gestation (50% vs. 16.8%, p <0.016). CMV-IgM demonstrates a low detection rate for non-primary maternal infection during pregnancy compared to primary infection (25% vs. 75.8%, p = 0.0008). CONCLUSION: Non-primary maternal CMV infection has an impact on the neonate. Although not readily diagnosed during pregnancy, knowledge of risk factors may aid in raising clinical suspicion.

Positive IgM in Congenital CMV Infection.

Neonatal serum detection of cytomegalovirus (CMV) immunoglobulin M (IgM) has low sensitivity in identifying congenital cytomegalovirus (cCMV). Several reports have endeavored to associate the presence/absence of IgM to disease severity. Data were collected for all infants with cCMV followed in our clinic. Infant outcome after birth was compared between infants who tested positive or negative. Sensitivity of positive IgM in diagnosing cCMV was 40.7%. The rate of symptomatic disease in those who tested positive was statistically higher (67.7%, P < .001). Odds ratio for symptomatic disease in infants with positive IgM born after a maternal primary infection was 3.47 (95% confidence interval = 1.7-7.1). Positive IgM was found in only 48.8% of symptomatic and 22.1% of asymptomatic children. Our results demonstrated a low sensitivity of IgM in diagnosing cCMV. However, while a positive IgM antibody for CMV is associated with a more symptomatic disease, it does not serve as a precise laboratory marker for a severity.

Clinical Implications for Children Born With Congenital Cytomegalovirus Infection Following a Negative Amniocentesis.

BACKGROUND: Recently, congenital cytomegalovirus (cCMV) infection was reported irrespective of a negative amniotic fluid prenatal analysis for cytomegalovirus (CMV). The question of whether this phenomenon represents low sensitivity of the test or late development of fetal infection (after amniocentesis) was discussed, but not answered. However, if late transmission is the rule, then infants born with cCMV after negative amniocentesis would be expected to carry better prognosis than those who tested positive. METHODS: Data of all infants with cCMV infection, followed in 2 pediatric centers from 2006 to 2015, were reviewed. Infant outcome after birth of symptomatic vs asymptomatic disease was compared with infants born after a negative amniocentesis (study group) and those with a positive amniocentesis (control group). RESULTS: Amniocentesis was performed in 301 pregnancies of our cohort of infants with cCMV and was negative for CMV in 47 (15.6%). There were fewer symptomatic cCMV neonates in the study group than in the control group (4.3% vs 25%; P < .001). Hearing impairment at birth was also less frequent in the study group (2.2% vs 17.4%; P = .012). None of the children in the study group had neurologic sequelae at long-term follow up, compared with 13 (14.1%) in the control group (P < .001). CONCLUSIONS: Although negative amniocentesis does not exclude cCMV, infants with cCMV born after a negative amniocentesis seldom present with mild clinical symptoms or cerebral ultrasound features at birth. These children also have a very good long-term outcome. Our findings support the theory of a late development of fetal infection, after the time of the amniocentesis.

Hearing outcome of infants with congenital cytomegalovirus and hearing impairment.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of childhood sensorineural hearing loss. Antiviral treatment has been shown to prevent hearing deterioration in these infants. However, studies focused on infants with hearing impairment at birth and on the specific degree of impairment and further improvement or deterioration are lacking. OBJECTIVE: To investigate the relationship between hearing status at birth and any change in hearing status at the end of a prolonged follow-up period, after receiving 12 months of antiviral treatment in children born with hearing impairment due to congenital cCMV. METHODS: Clinical, laboratory, radiological and audiological data of all infants with cCMV infection followed in our centre between 2005 and 2013 were reviewed. Treatment with antiviral medication for hearing impairment found during the neonatal period was12 months of gan/valganciclovir. Hearing studies were performed only on infants who had been followed up for more than 1 year after treatment. RESULTS: Hearing impairment at birth was found in 54 (36.2%) of the 149 infants diagnosed with symptomatic cCMV, and found in 77 affected ears; unilateral in 31 (57.4%) and bilateral in 23 (42.6%). After 1 year of antiviral treatment and a long-term follow-up of the 77 affected ears at baseline, 50 (64.9%) had improved, 22 (28.6%) remained unchanged and 5 (6.5%) had deteriorated. Most improved ears (38/50=76%) returned to normal hearing. Improvement was most likely to occur in infants born with mild or moderate hearing loss and less in those with severe impairment. CONCLUSIONS: We found that infants born with cCMV and hearing impairment, receiving 12 months of antiviral treatment, showed significant improvement in hearing status. The probability of hearing improvement seems inversely related to the severity of the impairment at birth.

Follow-up of infants with congenital cytomegalovirus and normal fetal imaging.

OBJECTIVE: To evaluate the outcome of infants with congenital cytomegalovirus (CMV) infection and normal fetal imaging. DESIGN: Retrospective cohort study. SETTING: Tertiary paediatric medical centre. PATIENTS: 98 infants born to mothers with primary CMV infection in the first and second trimesters (diagnosed by positive amniotic fluid findings) and normal fetal imaging. METHODS: Initial evaluation included confirmatory urine culture, complete blood count, liver and kidney function tests, funduscopy, brain ultrasound and hearing test. Follow-up included periodic neurological and developmental evaluation, hearing tests until age 5 and Bayley-III Developmental Scale (in some patients). MAIN OUTCOME MEASURES: The presence and rate of sequelae of congenital CMV. RESULTS: 52 (53.1%) infants received early antiviral treatment for central nervous system symptoms or signs, mainly lenticulostriatal vasculopathy on postnatal ultrasonography (88.5%). Sensorineural hearing loss was found on first examination in 16 infants (25 ears), of whom 10 also had cranial ultrasound findings; another five with late-onset hearing loss were also treated. The median follow-up time was 32 (12-83) months. Most infants with moderate and severe hearing loss were infected in the first trimester (10 vs 2, p=0.053). At the last assessment, eight children (10 ears) still had hearing loss, including two with bilateral loss who underwent a cochlear implant. The mean Bayley-III score was 102.6±10.3 (range 85-127). All 98 children attended regular educational institutions. CONCLUSIONS: Congenital CMV infection acquired from primary maternal infection with normal fetal imaging is associated with a high rate of subtle signs and symptoms after birth. Overall, intermediate-term outcome is good with a low rate of sequelae.

Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection.

OBJECTIVES: This study aimed to evaluate antenatal risk factors associated with symptomatic congenital cytomegalovirus (CMV) disease, following in utero vertical infection. METHODS: This study included a retrospective cohort of 155 neonates with congenital CMV infection, following primary maternal CMV infection during pregnancy, and were divided to symptomatic (n=95) and asymptomatic (n=60) newborns. RESULTS: Young maternal age (29.1±5.12 vs. 31.6±5.36 years, P=0.005), high risk occupation for viral exposure (20.0% vs. 11.7%, P=0.04), CMV IgG seroconversion at diagnosis (83.1% vs. 63.3%, P=0.005) and abnormal fetal MRI (11.6% vs. 0%, P=0.003) were found to be prognostic risk factors associated with symptomatic CMV disease of the newborn. Maternal febrile illness at diagnosis, IgG avidity, US findings and the timing of maternal infection were not associated with the occurrence of neonatal symptoms. CONCLUSIONS: Knowledge of the reported risk factors may assist in counseling parents with intra uterine CMV infection.

Lenticulostriated vasculopathy is a high-risk marker for hearing loss in congenital cytomegalovirus infections.

AIM: This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection. METHODS: We included all infants with cCMV infection who were followed in our clinic for more than a year with only LSV signs of brain involvement on initial brain ultrasound. Group one comprised 13 infants with no hearing impairment at birth who were not treated with gan/valganciclovir during 2006-2009. Group two was 51 infants with LSV and no hearing impairment who had been treated since mid-2009. Group three was 25 infants born with LSV and hearing loss, who had been treated from birth. Group four was 52 control infants born during the same period with asymptomatic cCMV. Hearing tests were performed during the neonatal period and every four to six months until four years of age. RESULTS: Hearing deterioration was more extensive in group one (85%) than in group two (0%, p < 0.001) and the asymptomatic group (10%, p < 0.001) and occurred more often in group four (10%) than in group two (0%, p = 0.008). CONCLUSION: Lenticulostriated vasculopathy was common in infants with cCMV infection and may serve as a sign of central nervous system involvement and further hearing deterioration. Antiviral treatment may be prudent in such infants.

Association of isolated polyhydramnios at or beyond 34 weeks of gestation and pregnancy outcome.

OBJECTIVE: To evaluate pregnancy outcome among women with isolated polyhydramnios at admission for labor at or beyond 34 weeks of gestation. METHODS: Retrospective cohort study at a tertiary medical center between 2007 and 2012. Isolated polyhydramnios was defined as amniotic fluid index (AFI) greater than 25 cm at admission in the absence of gestational or pregestational diabetes mellitus or fetal structural or chromosomal anomalies. Women with isolated polyhydramnios were compared with women with a normal AFI (5-25 cm). RESULTS: Overall, 31,376 women were eligible for analysis, of whom 215 (0.7%) had isolated polyhydramnios and 31,161 normal AFI. Women with isolated polyhydramnios had higher rates of labor induction (7.9% compared with 4.8%, P=.04) and cesarean delivery (12.1% compared with 5.1%, P<.001). They also had higher rates of placental abruption (0.9% compared with 0.2%, P=.02), abnormal or intermediate fetal heart rate (FHR) tracings (7.0% compared with 3.2%, P=.002), and prolonged first stage of delivery (6.0% compared with 1.4%, P<.001). Isolated polyhydramnios was also associated with higher rates of shoulder dystocia (1.9% compared with 0.3%, P<.001) and respiratory distress syndrome (0.5% compared with 0.03%, P=.001). On a multiple logistic regression model, isolated polyhydramnios was an independent risk factor for labor induction (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.01-2.8), cesarean delivery (adjusted OR 2.6, 95% CI 1.7-4.0), prolonged first stage of delivery (adjusted OR 3.6, 95% CI 1.97-6.7), abnormal or intermediate FHR tracings (adjusted OR 2.6, 95% CI 1.6-4.5), placental abruption (adjusted OR 8.4, 95% CI 2.00-35.4), shoulder dystocia (adjusted OR 3.4, 95% CI 1.2-9.7), and respiratory distress syndrome (adjusted OR 38.9, 95% CI 4.6-332.6). Mild isolated polyhydramnios (AFI 25.1-30.0) was independently associated with cesarean delivery, prolonged first stage of delivery, placental abruption, abnormal or intermediate FHR tracings, and shoulder dystocia. CONCLUSION: Isolated polyhydramnios at admission for labor at or beyond 34 weeks of gestation is associated with adverse obstetric and neonatal outcomes.