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Background: Despite major advances in the pharmacological treatment of hypertension in the non-pregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother beside normalizing the blood pressure values. Objective: to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy in accordance with the baseline hemodynamic findings STUDY DESIGN: prospective multicenter study including a population of women with de novo diagnosis of HDP. A noninvasive assessment of the following maternal parameters was done upon the hospital admission by means of USCOM (Ultrasound Cardiac Output Monitor) before any antihypertensive therapy was given: Cardiac Output (CO), Heart Rate (HR), Systemic Vascular Resistance (SVR), Stroke Volume (SV). The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and based on his preferences or on the local protocols used as 1st line a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol). The 1st line pharmacological treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: 1) Women with a hypodynamic profile (defined as low cardiac output [CO≤5L/min] and/or high systemic vascular resistance [SVR≥1300 dynes*s*cm]) who were administered oral nifedipine or alpha methyldopa. 2) Women with a hyperdynamic profile (defined as normal or high cardiac output [CO >5 L/min] and/or low systemic vascular resistances [SVR<1300 dynes*s*cm-]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between the women who were found to be treated with a hemodynamically appropriate or

Objective: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided. Study design: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years. Results: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls. Conclusions: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patient

Objectives: To compare ultrasound (US) and magnetic resonance imaging (MRI) in the assessment of mediastinal shift angles (MSAs) in fetuses affected by isolated left congenital diaphragmatic hernia (CDH). The use of MRI-MSA and US-MSA as prognostic factor for postnatal survival in fetal left CDH was also explored. Methods: This was an observational study of 29 fetuses with prenatally diagnosed isolated left CDH, assessed with both US and MRI examinations between January 2015 and December 2018. The US-MSA measurements performed within 2 weeks from the MRI assessment were considered for the analysis. The primary outcome was the postnatal survival rate. Results: No significant difference between US and MRI MSAs was detected (p =.419). Among the 29 cases, there were 21 alive infants, for an overall postnatal survival rate of 72.41%. After stratifying for postnatal survival, the best cutoffs with the highest discriminatory power in terms of sensibility and specificity were 42.1° for the US-MSA and 39.1° for the MRI-MSA. The performance of MRI-MSA in predicting postnatal survival was close to that of US-MSA in terms of sensitivity (62.5 versus 50.0%), specificity (80.9 versus 90.5%), positive predictive value (55.6 versus 66.7%), negative predictive value (85.0 versus 82.6%) and accuracy (75.9 versus 79.3%). There was no statistically significant difference between the two modalities (p >.05 for all). Conclusions: MRI and US can be interchangeably used for the assessment of MSA in prenatally diagnosed isolated left CDH. Moreover, MSA measured by both US and MRI was confirmed to be correlated with perinatal outcome in terms of survival.

Autoimmune diseases (AIDs) are associated with strong female preponderance and often present before or during the reproductive years; consequently, pregnancy and breastfeeding are topics of major interest for these patients. AIDs show different responses to pregnancy: some ameliorate, while others remain unchanged, and several AIDs aggravate. The response of the AIDs to the hormonal and immunological alterations of pregnancy reflects the different pathophysiology of each disease. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with multiple autoantibodies, multiorgan involvement, more aggressive therapy, and increased impact on pregnancy outcome. For the management of pregnancy in patients with SLE and/or APS, it is important to individuate the correct risk profile for each woman and timing for treatment. The optimal timing for starting or modulating treatment is at preconception assessment to influence the placentation. In this chapter, we discuss the management of pregnancy in patients with AIDs.

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case–control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22–25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26–34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

Objective: To establish consistent normal reference values for fetal anterior cerebral artery (ACA) and posterior cerebral artery (PCA) pulsatility index (PI) in prolonged pregnancy. Methods: This prospective cross-sectional observational study included singleton normal prolonged pregnancies into two study groups according to the gestational age: from 40 + 0 to 40 + 6 and from 41 + 0 to 41 + 6 weeks. The PI was assessed in both anatomical segments of ACA (ACA-S1 and ACA-S2) and of PCA (PCA-S1 and PCA-S2) with color Doppler imaging and pulsed Doppler examination, and reference centiles charts were generated. PI values from the two investigated segments of each vessel were also compared. Results: Data were obtained in 771 patients: n = 448 in the 40 + 0 and 40 + 6 weeks group, and n = 323 in the 41 + 0 and 41 + 6 weeks group. A moderate decrease in PI was observed as pregnancy progressed. No differences in PI values were found between the two anatomical segments of ACA and PCA. Conclusion: This study provides Doppler reference values for the fetal ACA and PCA PI. It also shows that Doppler examination could be performed indifferently in one of the two anatomical segments of these arteries.

Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear. Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome. Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed. Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms. Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.

Introduction: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly. Materials and Methods: We identified singleton fetuses with estimated fetal weight <10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses. Results: When comparing chest size, small fetuses had significantly lower thoracic circumferences median Z-scores (IQR) for GA = -4.82 (-6.15 to -3.51), BPD = -2.42 (-4.04 to -1.48), HC = -2.72 (-4.53 to -1.90), and FL = -1.60 (-2.87 to -0.71); p < 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median Z-scores (IQR) for GA = -1.59 (-2.79 to -0.16); p < 0.001, similar cardiac circumferences Z-scores for BPD = 0.29 (-0.65 to 1.28); p = 0.284 and HC = 0.11 (-1.13 to 0.96); p = 0.953, and higher cardiac circumferences Z-scores for FL = 0.94 (-0.05 to 2.13); p < 0.001. Conclusions: Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.

Background: The optimal treatment of women with primary antiphospholipid syndrome (APS) is still debated. About 20–30% of women with APS remain unable to give birth to healthy neonates despite conventional treatment, consisting of prophylactic-dose heparin and low-dose aspirin. These cases are defined “refractory obstetric APS”. The early identification of risk factors associated with poor pregnancy outcome could be the optimal strategy to establish criteria for additional therapies, such as hydroxychloroquine, steroids, intravenous immunoglobulin, and plasma exchange. Purpose: The aim of the present study was to review current literature about risk factors for poor pregnancy outcome. Search methods: The PubMed database was used to search for peer-reviewed original and review articles concerning risk factors for pregnancy outcome in APS from 1st January 1990 to 15th January 2018. Outcomes: History of pregnancy morbidity and/or thrombosis, the association with SLE and/or other autoimmune diseases are well known history-based predictive factors for obstetrical complications, such as miscarriage, maternal venous thromboembolism, intrauterine foetal demise, preeclampsia, and neonatal death. Moreover, laboratory findings associated with poor pregnancy outcome are:triple antiphospholipid antibodies aPL positivity, double aPL positivity, single aPL positivity, false-positive IgM for CMV, and hypocomplementemia. Triple positivity is confirmed as the most significant risk factor by a large body of evidence. Furthermore, the abnormal uterine arteries Doppler velocimetry results are confirmed to be strongly associated with poor pregnancy outcomes in APS. The good performance of the uterine arteries velocimetry, as a negative predictive factor, was reported by different studies. On the contrary, in case of abnormal uterine arteries results, the relevance of a careful surveillance is highlighted for the high risk of maternal-foetal complications. Nevertheless, this tool is a lat

Objective: Data concerning feasibility of the fetal cerebral Doppler examination in full term and late term pregnancy is lacking. Our purpose was to perform an evaluation of these arteries with power Doppler ultrasound, calculating the percentage of identification and measurement and the intraobserver reproducibility. Methods: This was a cross sectional study evaluating a population of 578 normally grown fetuses divided according to the week of examination. The first group included fetuses examined at week 40 (N = 323) and the second fetuses examined at week 41 (N = 255). The three major branches of the internal carotid artery (anterior, middle and posterior cerebral arteries, ACA, middle cerebral artery (MCA), posterior cerebral arteries (PCA)) and their anastomosis (A1, A2, P1, P2) were examined with power Doppler ultrasonography by three independent ultrasonographers. The proportion of vessel identified and measured was calculated and the reproducibility among the three operators was investigated. Results: The major arteries at the circle of Willis were fully identified/measured in 65/56 and 62/48% of fetuses at 40 and 41 weeks. The MCA obtained the higher percentage of identification and measurement at both periods (> 80 and >70%). The entire set of anastomosis were less frequently identified/measured at both periods (50/< 50% of cases), especially in the A2 segment. The best agreement was obtained in the MCA and the worst in the PCA-P1 segment. Conclusions: At 40 and 41 weeks, the fetal cerebral vessels, especially the MCA, are suitable for power Doppler evaluation, providing an interesting tool to evaluate fetal hemodynamics in full and late term pregnancy.

Lung ultrasound examination has been demonstrated to be an accurate imaging method to detect pulmonary and pleural conditions. During pregnancy, there is a need for rapid assessment of the maternal lung in patients with suspected coronavirus disease 2019. We report our experience on lung ultrasound examination in the diagnosis of coronavirus disease 2019 pneumonia in a pregnant woman. Typical ultrasound features of this pulmonary pathology, including diffuse hyperechoic vertical artifacts with thickened pleural line and “white lung” with patchy distribution, were observed. We suggest point-of-care lung ultrasound examination as a diagnostic imaging tool in pregnant women with suspected coronavirus disease 2019.

Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease due to transplacental passage of circulating anti-Ro/SSA and anti-La/SSB autoantibodies. It occurs in 2% of anti-Ro/SSA-exposed pregnancies, and recurrence rate is nine times higher in subsequent pregnancies. Aim of this review is to identify biomarkers of CHB and treatment strategies. The Ro-system is constituted by two polypeptides targeted by the anti-Ro52 and anti-Ro60 autoantibodies. The central portion of Ro52 (p200), more than the full amino-acid sequence of Ro-52, is recognized to be the fine specificity of anti-Ro associated to the highest risk of cardiac damage. If anti-p200 antibody should be tested, as biomarker of CHB, over standard commercial ELISAs is still debated. Recent studies indicate that type I-Interferon (IFN) can activate fibroblasts in fetal heart. In the mother the anti-Ro/La antibodies activate the type I IFN-signature, and maternal IFN-regulated genes correlate with a similar neonatal IFN-gene expression. Evaluation of maternal IFN-signature could be used as novel biomarker of CHB. The measurement of “mechanical” PR interval with weekly fetal echocardiogram (ECHO) from 16 to at least 24 weeks of gestation is strongly recommended for CHB prenatal diagnosis. However, ECHO screening presents some limitations due to difficult identification of first-degree block and possible occurrence of a complete block from a normal rhythm in few days. Maternal administration of Hydroxychloroquine from the tenth week of gestation, modulating toll-like receptor and autoantibody-dependent type I IFN activation on the fetus, has an important role in preventing CHB in pregnant women with high risk for recurrent CHB.

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Introduction: The aim of this study is to evaluate short- and long-term consequences in children born to women after different bariatric surgery (BS) procedures. Methods: A questionnaire survey was given to the mothers referred from 1994 to 2019 to our center for pregnancy and delivery management after BS procedures: (a) malabsorptive surgery, (b) restrictive procedures, and (c) combined restrictive-malabsorptive procedures. Results: Data from 74 children born after BS, aged 0 month to 12 years, were analyzed. The prevalence of children with underweight was 5.4%, normal weight 59.5%, overweight 16.2%, and obesity 18.9%. The prevalence of obesity was higher in children pre-school aged than that in school-aged ones. Neurodevelopmental disorders were more frequent if maternal BMI before bariatric surgery was ≥ 41 kg/m2 (p = 0.008), as well as if the pregnancy occurred less than 18 months after BS (p = 0.028). In school-aged children conceived within 18 months after BS, the highest risk of neurodevelopmental disorders (p = 0.028) and overweight (p = 0.018) was observed. The prevalence of neurodevelopmental disorders was much higher for small for gestational age babies (p = 0.048). Children born after biliopancreatic diversion (BPD) showed less maternal breastfeeding, shorter breastfeeding duration, more overweight, and more occurrence of atopic dermatitis in comparison with children born after other bariatric procedures. Conclusions: Postnatal health in children born to women after BS was impaired by long-term consequences and by other diseases later in life. Children born after BPD were particularly at higher risk for short and long term consequences when compared to children born after other BS procedures.

OBJECTIVE: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of foetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It's based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study is to develop a modern foetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound. METHODS: This is a retrospective analysis of 35 240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, foetuses with major malformations and /or chromosomal disorders and stillborn foetuses were excluded. RESULTS: An increasing trend of median neonatal weight, in comparison that with the previous Italian National Curve drawn up in 1975, was found. CONCLUSIONS: Combining data from two centres, a new foetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian foetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740-3930) and 46 (7-93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

Case-report: an intriguing case of successful pregnancy and lupus anticoagulant remission after gluten-free diet in a woman affected by coeliac disease and antiphospholipid syndrome.

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

Prognosis of pregnancies in women with antiphospholipid syndrome has dramatically improved over the past two decades using conventional treatment with low molecular weight heparin and low-dose aspirin. However, despite this regimen, 10–15% of antiphospholipid syndrome patients experience pregnancy losses. Several studies have been performed in order to identify risk factors predictive of complications. Thrombosis has been generally accepted as the key pathogenetic mechanism underlying pregnancy morbidity. However, the thrombogenic state alone is not able to explain all the different mechanisms leading to pregnancy failure. In fact, emerging evidence shows that complement pathway could play an important role in mediating clinical events in antiphospholipid syndrome. However, the exact mechanism through which complement mediates antiphospholipid syndrome complications remains unknown. Low complement levels (C3 and C4) are associated with poor pregnancy outcome in women with antiphospholipid syndrome in different studies. Hypocomplementemia could be indicated as an early predictor of adverse pregnancy outcome, available at the beginning of pregnancy for starting, if necessary, additional treatment to conventional therapy. However, future studies need to better understand the impact of low complement level on antiphospholipid syndrome pregnancy outcome.

BACKGROUND: Infants born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse outcomes than those born at 37 weeks of gestation or later. Aim of this paper is to examine risk factors for late preterm births and to investigate the complications of the transition period in late preterm infants (LPIs). METHODS: All consecutive late preterm deliveries, excluded stillbirths, were included. Maternal and neonatal data, need for delivery room resuscitative procedures, temperature at birth (T1) and two hours after the admission (T2) were analyzed in all LPIs stratified by Gestational Age (GA) and divided into three groups (34, 35 and 36 weeks). RESULTS: Two hundred seventy-six LPIs were analyzed. Pregnancy complications were present in 72 mothers (26.1 %), more frequently at 34 weeks of gestation respect to 35 and 36 weeks (p = 0.008, p = 0.006 respectively). Forty seven LPIs (17.1 %) needed for any resuscitation and 37 (13.4 %) were ventilated at birth. LPIs at 34 weeks were significantly more likely to receive ventilation respect to those at 35 and 36. At T1 the mean temperature resulted lower at 34 weeks respect to 36 weeks (p = 0.03). At T2 respect to T1, the rate of normothermic neonates increased at 35 and 36 weeks (p = 0.003, p = 0.005, respectively). Hypoglicemia rate was similar among the groups; 66.7 % of hypoglicemic neonates were hypothermic at T1. The rate of respiratory diseases and NICU admission decreased with increasing GA. Higher number of neonates ventilated at birth developed respiratory disorders respect to those unventilated (40.5 % vs 8.4 %; p < 0.001). CONCLUSIONS: Transition period in LPIs may become critical, as resuscitation strategies can be required and heat loss can occur. LPIs, especially at 34 gestational weeks, are higher-risk group needing adequate and targeted management at birth.

Background: Neonatal blueberry muffin lesions are rare cutaneous eruptions, presenting as transient, non-blanching, red-violaceous papules, mostly localized in the trunk, head and neck, attributable to a marked dermal hematopoietic activity. Congenital infections of the TORCH complex (toxoplasmosis, other, rubella, cytomegalovirus and herpes) and hematological disorders have been classically associated with this neonatal dermatological manifestation. We report for the first time an unusual presentation of blueberry muffin lesions in a neonate born from a mother affected by severe anemia during pregnancy. Case presentation: A male, white Caucasian, neonate showed a cutaneous rash at birth, suggestive of "blueberry muffin"-like lesions. These cutaneous lesions were associated with marked elevation of the circulating nucleated red blood cells, and with ultrasound findings of peculiar brain ischemic porencephalic lesions. The clinical features of spontaneous disappearance and the association with marked erythroblastosis strongly suggest that these dermatological findings may be the consequence of an extramedullary hematopoiesis unexpectedly evoked by the intrauterine chronic exposure to hypoxia caused by severe maternal anemia. Conclusions: In conclusion, fetal hypoxia secondary to severe maternal anemia may play a causative and unreported role in the development of neonatal blueberry muffin lesions.