Dietary Intervention during Weaning and Development of Food Allergy: What Is the State of the Art?

Food allergy (FA) affects approximately 6-8% of children worldwide causing a significant impact on the quality of life of children and their families. In past years, the possible role of weaning in the development of FA has been studied. According to recent studies, this is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collect the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food. As shown in most of the studies included in this review, early food introduction did not show a potential protective role against FA development, and we conclude that further evidence is needed from future clinical trials.

Molecular Mechanism and Clinical Effects of Probiotics in the Management of Cow's Milk Protein Allergy.

Cow's milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or "dysbiosis". Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics' efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Probiotics Function in Preventing Atopic Dermatitis in Children.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role of probiotics in AD prevention has generated considerable interest. As many clinical studies show, the gut microbiota is able to modulate systemic inflammatory and immune responses influencing the development of sensitization and allergy. Probiotics are used increasingly against AD. However, the molecular mechanisms underlying the probiotics mediated anti-allergic effect remain unclear and there is controversy about their efficacy. In this narrative review, we examine the actual evidence on the effect of probiotic supplementation for AD prevention in the pediatric population, discussing also the potential biological mechanisms of action in this regard.

Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice?

OBJECTIVE: Combined oral contraceptives (COC) and progestogens are widely used for the treatment of endometriosis. The objective of the study is to compare the efficacy of dienogest 2 mg vs continuous oral levonorgestrel/EE (levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg) on ovarian endometriomas, deep infiltrating endometriosis (DIE), chronic pelvic pain (CPP), dyspareunia, analgesic use, quality of life (QoL), compliance and side effects. METHODS: Prospective cohort study. Two cohorts of patients with endometriosis, 50 taking dienogest (group A) and 50 taking continuous levonorgestrel/EE (group B), were evaluated at the beginning of therapy (t0), after 3 (t3) and 6 months (t6). Size of endometriomas, DIE, QoL, pain symptoms, and side effects were assessed. RESULTS: Dienogest was significantly effective on CPP (p = .002), dyspareunia (p = .021) ovarian endometriomas (p = .015) and DIE lesions reduction (p = .014). Levonorgestrel/EE was significantly effective on dyspareunia (p = .023). Analgesics consumption significantly decreased in both groups (p < .001). Both treatments significantly improved the QoL. Over 6 months a significant improvement was found, more frequently in patients taking dienogest. The only side effect that both groups complained about was vaginal bleeding, present in the first 3 months of treatment (p < .001). CONCLUSIONS: Both treatments are effective and safe for patients with endometriosis. Patients compliance and side effects are similar in both groups, however, there was a significantly higher reduction in endometriotic lesions, pain symptoms, and improvement of the QoL in women taking dienogest than in women taking continuous COC.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Evaluation of Parametrial Status in Locally Advanced Cervical Cancer Patients after Neoadjuvant Chemotherapy: A Prospective Study on Diagnostic Accuracy of Three-Dimensional Transvaginal Ultrasound.

OBJECTIVES: To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. METHODS: Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. RESULTS: We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (p = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (p = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. CONCLUSION: In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.

Fetus morphology changes by second-trimester ultrasound in pregnant women drinking alcohol.

Fetal alcohol spectrum disorders (FASDs) are a group of negative conditions occurring in children exposed to alcohol during gestation. The early discovery of FASD is crucial for mother and infant follow-ups. In this study, we investigated in pregnant women the association between urine ethylglucuronide (EtG-a biomarker of alcohol drinking) and indicators of the physical characteristics of FASD by prenatal ultrasound in the second trimester of gestation. We also correlated these data with the AUDIT-C, T-ACE/TACER-3, TWEAK, and food habit diary, screening questionnaires used to disclose alcohol drinking during pregnancy. Forty-four pregnant women were randomly enrolled and examined for ultrasound investigation during the second trimester of gestation. Urine samples were provided by pregnant women immediately after the routine interviews. EtG determinations were performed with a cutoff established at 100 ng/mL, a value indicating occasional alcohol drinking. Fifteen of the enrolled pregnant women overcame the EtG cutoff (34.09%). Analysis of variance (ANOVA) revealed that the fetuses of the positive EtG pregnant women had significantly longer interorbital distance and also significantly increased frontothalamic distance (P's < 0.02). Quite interestingly, no direct correlation was found between EtG data and both food diary and AUDIT-C. However, a significant correlation was observed between urinary EtG and T-ACE (r = 0.375; P = 0.012) and between urinary EtG and TWEAK (r = 0.512; P < 0.001) and a concordance with all questionnaire for EtG values higher than 500 ng/mL. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy by urine EtG may disclose FASD-related damage in the fetus.

Diagnosis & management of imported malaria in pregnant women in non-endemic countries.

Malaria in pregnancy is an important cause of maternal and foetal morbidity and is a potentially life-threatening infection. With ever-growing global exchanges, imported malaria in pregnancy is becoming an issue of concern in non-endemic countries where women, because of low immunity, have higher risk of severe diseases and death. Malaria in pregnancy is a dangerous condition which can be associated with important consequences for both mother and child such as stillbirth, low birth weight, maternal anaemia. In non-endemic-countries it is more frequent in its severe form which can lead to maternal death if not treated adequately. Specific anti-malarial interventions such as the use of repellents and insecticide treated bed nets in addition to chemoprophylaxis should be used by pregnant women if they are travelling to endemic areas. In cases of confirmed infection, specific treatment regimens vary according to gestational age and the presence of complications. Malaria should be considered a global health problem, increasingly involving western countries. Clinicians all over the world need to be prepared for this emerging disease both in terms of prevention and therapy.

An observational study to assess Italian obstetrics providers' knowledge about preventive practices and diagnosis of congenital cytomegalovirus.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can be easily prevented by hygienic measures. Up to date the majority of the studies in literature highlighted a reduction in cCMV antenatal counseling and its prevention. Our purpose was to evaluate obstetrics providers' knowledge about cCMV infection, management and the behavioral practices to avoid it. METHODS: This is a cross-sectional survey carried out in Umberto I Hospital, "Sapienza" University of Rome between November 2019 and January 2020. We recruited 148 specialists and residents in Obstetrics and Gynecology through online anonymous multiple-choice 13-questions, 10 min-survey comparing responses between the two groups. RESULTS: A total of 94.6% of all participants said they always prescribe cytomegalovirus (CMV) serum screening: 73.6% of them regularly counsel about preventive practices, with specialists recording higher percentages (85.4 vs. 65.1%, p<0.005). We identified a good knowledge about the diagnostic pathway, but only 58.1% of our population knows the correct time of late amniocentesis. 12.2% of providers do not consider magnetic resonance (MRI) as a complementary exam. CONCLUSIONS: Prevention of maternal seroconversion is crucial: even if our data show an acceptable knowledge about antenatal counseling, we encourage clinicians to firmly inform and educate women about behavioral measures.

Obstetrical outcomes in women with history of breast cancer: a systematic review and meta-analysis.

PURPOSE: Potential risk of adverse obstetrical outcomes has been shown among breast cancer survivors. Therefore, the aim of this systematic review and meta-analysis was to evaluate the relationship between history of breast cancer (BC) and obstetrical outcomes. METHODS: PubMed, EMBASE, and Medline were searched from the inception of each database to April 2019. Selection criteria included prospective and retrospective cohort studies of BC pregnant survivors. The meta-analysis was performed by computing odds ratios (ORs) using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale and the review was registered with PROSPERO number CRD42019127716. RESULTS: Four studies, including 1466 cases of BC survivors and 6,912,485 controls, were included. Compared with controls, a higher incidence of obstetrical complication was found in women with history of BC. The incidence of preterm birth (PTB) in the study group was 11.05% compared with 7.79% in the control group (1.68, 95% confidence interval 1.43-1.99). Breast cancer history was also associated with low birth weight (LBW) (study group: 9.26% vs. control group: 5.54%, 1.88, CI 95% 1.55-2.27), cesarean section (CS) (study group: 19.76% vs. control group 10.81%, 1.78, CI 95% 1.39-2.27), intrauterine fetal death (IUFD) (study group: 0.004% vs. control group 0.36%, of 1.25 CI 95% 0.36-4.35), and fetal anomalies (study group: 5.8% vs. control group: 4.26%, 1.45 CI 95% 1.01-2.09). CONCLUSIONS: History of BC was associated with adverse obstetrical outcomes.

To evaluate the feasibility of magnetic resonance imaging in predicting unusual site ectopic pregnancy: a retrospective cohort study.

OBJECTIVE: To evaluate the accuracy of pelvic MRI in the diagnosis of unusual ectopic pregnancy (EP), when ultrasound (US) examination is inconclusive. METHODS: We retrospectively reviewed the medical records of 150 patients with suspected EP. Clinical, US and MRI features of 15 unusual EPs were analysed. Two radiologists independently reviewed each case resolving by consensus any diagnostic discrepancy. Interobserver agreement was assessed using the Cohen κ test. RESULTS: MRI displayed a gestational sac-like structure surrounded by a thick wall in all cases. The thick wall displayed hyperintensity in 41 %, isointensity in 35 % and hypointensity in 24 % of cases on T1-weighted images. Diffusion- and fat saturation T1-weighted images were the most accurate sequences, as they enabled identification of 15/15 and 14/15 patients, respectively. Although US was false negative in detecting cervical and uterine infiltration underlying the caesarean scar, MRI was able to identify the invasion. Interobserver agreement was very good for all sequences (κ=0.892-1.0). CONCLUSIONS: MRI plays an important role in the early diagnosis of unusual EP. It should be considered after negative US findings, providing accurate evaluation of the site and the possible infiltration of these lesions, which help in the management of these patients. KEY POINTS: • MRI is being increasingly used as a problem-solving modality in ectopic pregnancy. • MRI plays an important role in early diagnosis of unusual ectopic pregnancy. • Knowledge of MRI features in EP is essential to determinate appropriate management.

Sonohysterosalpingography: Comparison of foam and saline solution.

PURPOSE: To compare sonohysterosalpingography (sono-HSG) with foam instillation (HyFoSy) versus saline solution (HyCoSy) in the evaluation of tubal patency. METHODS: We prospectively enrolled 37 infertile women, scheduled for laparoscopy. The women were randomized into two groups: HyFoSy (group I) and HyCoSy (group II). The patients of both groups underwent laparoscopy with dye test. We assessed the diagnostic performance (sensitivity, specificity, and overall accuracy) of HyFoSy and HyCoSy, compared with laparoscopy and dye test, in the assessment of tubal patency. RESULTS: Sono-HSG findings in tubal patency assessment obtained in the HyFoSy group were concordant with laparoscopic results in 94.4% of cases, with a sensitivity of 87.5% and a specificity of 100%, whereas in the HyCoSy group, concordance occurred in only 57.8% of examinations, with a sensitivity of 50% and a specificity of 66.6%. CONCLUSIONS: HyFoSy allows a more accurate diagnosis of tubal patency compared with HyCoSy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:67-71, 2017.

Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review.

This systematic review focuses on the literature evidence for residual ovarian function during treatment with hormonal contraceptives. We reviewed all papers which assessed residual ovarian activity during hormonal contraceptive use, using endocrine markers such as serum anti-Müllerian hormone (AMH) concentrations, FSH, LH, oestradiol, progesterone and sonographic markers such as antral follicle count (AFC), ovarian volume and vascular indices. We considered every type (oestroprogestin or only progestin) and dosage of hormonal contraceptive and every mode of administration (oral, vaginal ring, implant, transdermal patch). We performed an electronic database search for papers published from 1 January 1990 until 30 November 2015 using PubMed and MEDLINE. We pre-selected 113 studies and judged 48 studies suitable for the review. Most studies showed that follicular development continues during treatment with hormonal contraceptives, and that during treatment there is a reduction in serum concentrations of FSH, LH and oestradiol, and also a reduction in endometrial thickness, ovarian volume and the number and size of antral follicles. The ovarian reserve parameters, namely AFC and ovarian volume, are lower among users than among non-users of hormonal contraception; regarding the effect of hormonal contraception on AMH, there are still controversies in the literature.

Transabdominal ultrasound-guided injection of methotrexate in the treatment of ectopic interstitial pregnancies.

PURPOSE: In a retrospective observational study, we evaluated the feasibility and safety of medical therapy with transabdominal ultrasound-guided injection of methotrexate (MTX) into the gestational sac (GS) in patients with interstitial ectopic pregnancies. METHODS: Fourteen interstitial ectopic pregnancies were treated with transabdominal ultrasound-guided injection of MTX (25 mg). All patients were hemodynamically stable. In all patients, the 10-cm distance between the GS and vaginal fornices was ≥10 cm, making transvaginal injection difficult. To evaluate feasibility and safety of the procedure, we assessed complications clinically and with imaging during a 1-year follow-up. RESULTS: In all 14 patients, MTX injected locally into the GS successfully terminated the interstitial pregnancy, thereby avoiding surgery. There was no complications during follow-up. CONCLUSIONS: The successful outcome in our patients suggests that the transabdominal route is feasible and safe as a nonsurgical option for terminating an ectopic interstitial pregnancy in patients in whom the transvaginal route is contraindicated or difficult, provided the patients are properly selected and operators have sufficient experience with the technique.

Hemorrhage of cerebral cavernous malformation in third trimester of pregnancy.

Cerebral cavernous malformation is a rare but important cause of cerebral hemorrhage in pregnancy and puerperium. In pregnancy, cavernomas can more easily bleed as a result of increased female hormones and growth factors such as vascular endothelial growth factor. We present the case of a pregnant woman who had been diagnosed with a cerebral cavernoma about ten years previously, after repeated headache episodes; at the 28th week of pregnancy the woman was hospitalized for epileptic seizures and active bleeding from the anterior cerebral artery. We describe the management of the case, the decision for a preterm delivery and for a resolutive neurosurgical procedure.

Prenatal Alcohol Exposure and Metabolic Disorders in Pediatrics: The Role of the Oxidative Stress-A Review of the Literature.

Prenatal alcohol exposure is responsible for increasing chronic disease risk in later life, including obesity and metabolic syndrome. Alcohol drinking may compromise endogenous antioxidant capacity, causing an increase in free radicals and reactive oxygen species in the newborn. Excessive reactive oxygen species could attack the cellular proteins, lipids, and nucleic acids, leading to cellular dysfunction. Moreover, oxidative stress could play a crucial role in the altered synthesis and release of neurotrophins and progressive mitochondrial modifications with uncontrolled apoptosis. This narrative review aims to underline the important role of alcohol abuse in oxidative stress events and consequent metabolic and neurocognitive impairments in children exposed to alcohol during gestational life.

Myopathy complicating lupus pregnancy.

Systemic lupus erythematosus was diagnosed in a 34-year-old pregnant woman because of leukopenia, typical skin rash, clinical and biochemical signs of muscle involvement, and positive serology (antinuclear antibodies and anti-double-stranded DNA). Corticosteroids and hydroxychloroquine (HCQ) were started at 18 weeks of gestation with overall benefit except for muscle involvement, which proved resistant even to higher dose of corticosteroids and high-dose intravenous immunoglobulin. Muscle biopsy showed signs of HCQ toxicity, and the drug was stopped. After withdrawal, muscle involvement disappeared. Hydroxychloroquine could be safely reintroduced some months after delivery. It is hypothesized that pregnancy may have represented the second "hit" in this patient with systemic lupus erythematosus necessary for the rapid development of HCQ-related myopathy.