High rates of neonatal polycythemia and hyperbilirubinemia during the first phase of COVID-19 pandemic in Italy: a single-center experience.

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.

Olfactory sensory and perceptual evaluation in newborn infants: A systematic review.

Fetuses are able to process olfactory stimuli present in the womb and continue to show a preference for these odors for months after birth. Despite the accumulated knowledge about their early ability to perceive odors, there is a lack of validated scales for odor response in newborns. The evaluation of reactions of the olfactory system to environmental stimuli in infants has been defined by methodological theoretical approaches of experimental and clinical assessment tools. These approaches are mainly based on psychophysical approaches and predominantly use behavioral and physiological measures. Examples can be found in studies describing early abilities of newborn babies for behaviors or heart rate variability showing memory of maternal food preferences or mother's breast milk. This systematic review aimed to determine whether validated odor assessment tools can be feasibly used in studies. Particularly in light of the current COVID-19 pandemic and evidence of associated olfactory impairment resulting from SARS-COV-2 infection, the study is also motivated by the need for tools to assess olfactory function in neonates.

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate.

Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4+ T cells and CD8+ T cells, increased percentages of natural killer cells, Vδ2+ γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.

Vertical transmission of SARS-CoV-2: A prospective cross-sectional study from a tertiary center.

The aim was to investigate the association of the delivery mode and vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through the samples of vaginal secretions, placenta, cord blood, or amniotic fluid as well as the neonatal outcomes. This cross-sectional study presents an analysis of prospectively gathered data collected at a single tertiary hospital. Sixty-three pregnant women with confirmed coronavirus disease 2019 (COVID-19) participated in the study. Vertical transmission of SARS-CoV-2 was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) tests and blood tests for immunoglobulin G (IgG)-immunoglobulin M (IgM) antibodies. All patients were in the mild or moderate category for COVID-19. Only one placental sample and two of the vaginal secretion samples were positive for SARS-CoV-2. Except for one, all positive samples were obtained from patients who gave birth by cesarean. All cord blood and amniotic fluid samples were negative for SARS-CoV-2. Two newborns were screened positive for COVID-19 IgG-IgM within 24 h after delivery, but the RT-PCR tests were negative. A positive RT-PCR result was detected in a neof a mother whose placenta, cord blood, amniotic fluid, and vaginal secretions samples were negative. He died due to pulmonary hemorrhage on the 11th day of life. In conclusion, we demonstrated that SARS-CoV-2 can be detectable in the placenta or vaginal secretions of pregnant women. Detection of the virus in the placenta or vaginal secretions may not be associated with neonatal infection. Vaginal delivery may not increase the incidence of neonatal infection, and cesarean may not prevent vertical transmission. The decision regarding the mode of delivery should be based on obstetric indications and COVID-19 severity.

Association of Maternal Perinatal SARS-CoV-2 Infection With Neonatal Outcomes During the COVID-19 Pandemic in Massachusetts.

Importance: The incidence of mother-to-newborn SARS-CoV-2 transmission appears low and may be associated with biological and social factors. However, data are limited on the factors associated with neonatal clinical or viral testing outcomes. Objective: To ascertain the percentage of neonates who were born to mothers with positive SARS-CoV-2 test results during the birth hospitalization, the clinical and sociodemographic factors associated with neonatal test result positivity, and the clinical and virological outcomes for newborns during hospitalization and 30 days after discharge. Design, Setting, and Participants: This multicenter cohort study included 11 academic or community hospitals in Massachusetts and mother-neonate dyads whose delivery and discharge occurred between March 1, 2020, and July 31, 2020. Eligible dyads were identified at each participating hospital through local COVID-19 surveillance and infection control systems. Neonates were born to mothers with positive SARS-CoV-2 test results within 14 days before to 72 hours after delivery, and neonates were followed up for 30 days after birth hospital discharge. Exposures: Hypothesized maternal risk factors in neonatal test result positivity included maternal COVID-19 symptoms, vaginal delivery, rooming-in practice, Black race or Hispanic ethnicity, and zip code-derived social vulnerability index. Delivery indicated by worsening maternal COVID-19 symptoms was hypothesized to increase the risk of adverse neonatal health outcomes. Main Outcomes and Measures: Primary outcomes for neonates were (1) positive SARS-CoV-2 test results, (2) indicators of adverse health, and (3) clinical signs and viral testing. Test result positivity was defined as at least 1 positive result on a specimen obtained by nasopharyngeal swab using a polymerase chain reaction-based method. Clinical and testing data were obtained from electronic medical records of nonroutine health care visits within 30 days after hospital discharge. Results: The cohort included 255 neonates (mean [SD] gestational age at birth, 37.9 [2.6] weeks; 62 [24.3%] with low birth weight or preterm delivery) with 250 mothers (mean [SD] age, 30.4 [6.3] years; 121 [48.4%] were of Hispanic ethnicity). Of the 255 neonates who were born to mothers with SARS-CoV-2 infection, 225 (88.2%) were tested for SARS-CoV-2 and 5 (2.2%) had positive results during the birth hospitalization. High maternal social vulnerability was associated with higher likelihood of neonatal test result positivity (adjusted odds ratio, 4.95; 95% CI, 1.53-16.01; P = .008), adjusted for maternal COVID-19 symptoms, delivery mode, and rooming-in practice. Adverse outcomes during hospitalization were associated with preterm delivery indicated by worsening maternal COVID-19 symptoms. Of the 151 newborns with follow-up data, 28 had nonroutine clinical visits, 7 underwent SARS-CoV-2 testing, and 1 had a positive result. Conclusions and Relevance: The findings emphasize the importance of both biological and social factors in perinatal SARS-CoV-2 infection outcomes. Newborns exposed to SARS-CoV-2 were at risk for both direct and indirect adverse health outcomes, supporting efforts of ongoing surveillance of the virus and long-term follow-up.

Vertical transmission of Severe Acute Respiratory Syndrome Coronavirus 2: A scoping review.

INTRODUCTION: The evidence for vertical transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is not well established. Therefore, the objective of this review is to summarize emerging evidence on the vertical transmission of Severe Acute Respiratory Syndrome Coronavirus 2. METHODS: We conducted a systematic search in PubMed, CINAHL, Web of Science, SCOPUS, and CENTRAL. Likewise, a search for preprint publications was conducted using MedRxiv and Research Square. Studies that addressed vertical transmission of SARS-CoV-2 (concept) among pregnant women infected by Covid-19 (population) in any setting (community, hospital, or home) in any country or context were considered for inclusion. Any types of studies or reports published between December 2019 and September 2020 addressing the effects of SARS-CoV-2 on pregnant women and their newborn babies were included. Studies were screened for eligibility against the inclusion criteria for the review by two reviewers. RESULTS: We identified 51 studies reporting 336 newborns screened for COVID-19. From the 336 newborns screened for COVID-19, only 15 (4.4%) were positive for throat swab RT-PCR. All neonates with positive throat swab RT-PCR were delivered by cesarean section. Among neonates with throat swab SARS-CoV-2 positive only five (33.3%) had concomitant placenta, amniotic fluid, and cord blood samples tested, of which only one amniotic fluid sample is positive for RT PCR. Five neonates had elevated IgG and IgM but without intrauterine tissue tested. Four neonates had chest imaging suggestive of COVID-19 pneumonia. CONCLUSION: Currently there is not enough evidence on vertical virologic transmission of COVID-19 infection during the third trimester of pregnancy. Additionally, there is no evidence to support cesarean delivery, abstaining from breast feeding nor mother and infant separation. Further research involving an adequate sample size of breast milk, placenta, amniotic fluid, and cord blood to ascertain the possibility of vertical transmission and breast milk transfer is needed.

Presumptive Neonatal Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019.

OBJECTIVE: The study aimed to alert the neonatal community to the possibility of multisystem inflammatory syndrome in children (MIS-C) like disease in critically ill neonates born to mothers with coronavirus disease 2019 (COVID-19). STUDY DESIGN: Diagnosis of MIS-C like disease was pursued after echocardiography showed severely depressed ventricular function and pathological coronary artery dilation in the setting of medically refractory multisystem organ failure and maternal COVID-19 infection. The neonate did not respond to standard medical therapy, and there was no alternative disease that could explain the clinical course. High index of clinical suspicion coupled with low risk of intravenous immunoglobulin (IVIG) prompted us to pursue IVIG administration even though the neonate did not meet classic criteria for MIS-C. RESULT: Following treatment with IVIG, there was rapid clinical improvement. Ventricular function improved within 15 hours and coronary artery dilation resolved in 8 days. There was no recurrence of disease during follow-up. CONCLUSION: COVID-19 associated MIS-C like disease has not been well described in neonates. As typical features may be conspicuously absent, a high index of suspicion is warranted in critically ill neonates born to mothers with COVID-19. Echocardiography may provide critical diagnostic information and narrow the differential diagnosis. KEY POINTS: · COVID-19 associated MIS-C can present in neonates.. · Echocardiography is helpful in raising suspicion for MIS-C in neonates.. · Consider MIS-C in the differential diagnosis of ill neonates born to mothers with COVID-19..

In Utero Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Evidence for in utero transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is growing but not definitive. We present a case of neonatal infection that supports in utero transmission of SARS-CoV-2 and provides insight into the hematogenous spread from mother to fetus.

Longitudinal Survey of COVID-19 Burden and Related Policies in U.S. Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to determine the prevalence of confirmed novel coronavirus disease 2019 (COVID-19) disease or infants under investigation among a cohort of U.S. neonatal intensive care units (NICUs). Secondarily, to evaluate hospital policies regarding maternal COVID-19 screening and related to those infants born to mothers under investigation or confirmed to have COVID-19. STUDY DESIGN: Serial cross-sectional surveys of MEDNAX-affiliated NICUs from March 26 to April 3, April 8 to April 19, May 4 to May 22, and July 13 to August 2, 2020. The surveys included questions regarding COVID-19 patient burden and policies regarding infant separation, feeding practices, and universal maternal screening. RESULTS: Among 386 MEDNAX-affiliated NICUs, responses were received from 153 (42%), 160 (44%), 165 (45%), 148 (38%) across four rounds representing an active patient census of 3,465, 3,486, 3,452, and 3,442 NICU admitted patients on the day of survey completion. Confirmed COVID-19 disease in NICU admitted infants was rare, with the prevalence rising from 0.03 (1 patient) to 0.44% (15 patients) across the four survey rounds, while the prevalence of patients under investigation increased from 0.8 to 2.6%. Hospitals isolating infants from COVID-19-positive mothers fell from 46 to 20% between the second and fourth surveys, while centers permitting direct maternal breastfeeding increased 17 to 47% over the same period. Centers reporting universal severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) screening for all expectant mothers increased from 52 to 69%. CONCLUSION: Among a large cohort of NICU infants, the prevalence of infants under investigation or with confirmed neonatal COVID-19 disease was low. Policies regarding universal maternal screening for SARS-CoV-2, infant isolation from positive mothers, and direct maternal breastfeeding for infants born to positive mothers are rapidly evolving. As universal maternal screening for SARS-CoV-2 becomes more common, the impact of these policies requires further investigation. KEY POINTS: · In this cohort, neonatal COVID-19 is rare.. · Policies regarding isolation and breastfeeding for infants are rapidly evolving.. · Most hospitals are now providing universal screening for expectant mothers for SARS-CoV-2..

Severe Neonatal Coronavirus Disease 2019 Presenting as Acute Respiratory Distress Syndrome.

Since initial identification of severe acute respiratory syndrome coronavirus 2 in 2019, the virus has proved to be highly transmissible, resulting in a global pandemic with emerging reports of infected neonates. This report highlights a severe case of neonatal coronavirus disease 2019 with acute respiratory distress syndrome.

Death of a neonate with suspected coronavirus disease 2019 born to a mother with coronavirus disease 2019 in Iran: a case report.

INTRODUCTION: A novel coronavirus named severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019. The virus, known as COVID-19, is recognized as a potentially life-threatening disease by causing severe respiratory disease. Since this virus has not previously been detected in humans, there is a paucity of information regarding its effects on humans. In addition, only limited or no information exists about its impact during pregnancy. CASE PRESENTATION: In the present case study, we report the death of a neonate born to a 32-year-old mother with coronavirus disease 2019 in Ilam, Iran, with Kurdish ethnicity. We report the infection and death of a neonate in Iran with a chest X-ray (CXR) marked abnormality 2 hours after birth demonstrating coronavirus disease 2019 disease. The neonate was born by elective cesarean section, the fetal health was assessed using fetal heart rate and a non-stress test before the birth, and there was no evidence of fetal distress. All the above-mentioned facts and radiographic abnormalities suggested that coronavirus disease 2019 is involved. CONCLUSIONS: In this case study, we report the death of a neonate born to a mother with coronavirus disease 2019, 11 hours after birth. There is a paucity of data on the vertical transmission and the adverse maternal-fetal consequences of this disease, so vertical transmission from mother to child remains to be confirmed.

Coronavirus infection in neonates: a systematic review.

OBJECTIVE: To summarise currently reported neonatal cases of SARS-CoV-2 infection. METHODS: A search strategy was designed to retrieve all articles published from 1 December 2019 to 12 May 2020, by combining the terms 'coronavirus' OR 'covid' OR 'SARS-CoV-2') AND ('neonat*' OR 'newborn') in the following electronic databases: MEDLINE/Pubmed, Scopus, Web of Science, MedRxiv, the Cochrane Database of Systematic Review and the WHO COVID-19 database, with no language restrictions. Quality of studies was evaluated by using a specific tool for assessment of case reports and/or case series. RESULTS: Twenty-six observational studies (18 case reports and 8 case series) with 44 newborns with confirmed SARS-CoV-2 infection were included in the final analysis. Studies were mainly from China and Italy. Half of neonates had a documented contact with the infected mother and one out of three infected neonates was admitted from home. Median age at diagnosis was 5 days. One out of four neonates was asymptomatic, and the remaining showed mild symptoms typical of acute respiratory infections and/or gastrointestinal symptoms. The majority of neonates were left in spontaneous breathing (room air) and had good prognosis after a median duration of hospitalisation of 10 days. CONCLUSIONS: Most neonates with SARS-CoV-2 infection were asymptomatic or presented mild symptoms, generally were left in spontaneous breathing and had a good prognosis after median 10 days of hospitalisation. Large epidemiological and clinical cohort studies, as well as the implementation of collaborative networks, are needed to improve the understanding of the impact of SARS-CoV-2 infection in neonates.

A Case Report of Neonatal 2019 Coronavirus Disease in China.

In December 2019, the coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and now has spread in many countries. Pregnant women are a population susceptible to COVID-19 and are more likely to have complications and even progress to severe illness. We report a case of neonatal COVID-19 in China with pharyngeal swabs testing positive by real-time reverse-transcription polymerase chain reaction assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

The clinical course of SARS-CoV-2 positive neonates.

The COVID-19 pneumonia was firstly reported in Wuhan, China, in December 2019. The disease had a rapid spread all over the word becoming an international public health emergency. Limited data were available on COVID-19 positive neonates. We reviewed relevant literature to understand the clinical course of disease and transmission routes in affected neonates. The aim of the study was evaluating the clinical course and prognosis of SARS-CoV-2 positive neonates. Based on current literature, the hypothesis of vertical transmission of SARS-CoV-2, though conceivable, remains unproven. A research conducted on PubMed database from December 2019 to April 27, 2020 revealed that were reported 25 neonates affected by SARS-CoV-2. Main symptoms were fever, cough, or shortness of breath but often these neonates did not show other symptoms during length stay in hospital. No deaths occurred.

Clinical and Imaging Features of COVID-19 in a Neonate.

We report the clinical history, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in a neonate whose mother was also a patient. The newborn was the youngest patient with COVID-19 in the world at the time he was diagnosed. This case has brought more attention and understanding to the epidemic and mode of transmission of the disease.

Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2.

OBJECTIVE: To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. STUDY DESIGN: This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). RESULTS: Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. CONCLUSION: Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. KEY POINTS: · Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth.. · Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth.. · Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed..