key: cord-0807889-oz1qo259 authors: Nayak, Manas Kumar; Panda, Santosh Kumar; Panda, Subhra Snigdha; Rath, Soumini; Ghosh, Arpan; Mohakud, Nirmal Kumar title: Neonatal Outcomes of Pregnant Women With COVID-19 in a Developing Country Setup date: 2021-05-18 journal: Pediatr Neonatol DOI: 10.1016/j.pedneo.2021.05.004 sha: dd8535da8d28bbb2c93c92a291a71d0c907ad95d doc_id: 807889 cord_uid: oz1qo259 Background Current evidence on vertical transmission of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and neonatal outcome among exposed newborns is emerging and posing a challenge for preventive interventions. Perinatal transmission to the neonates especially during breastfeeding and rooming in is also relatively unknown. Methods This prospective observational study was conducted in Kalinga Institute of Medical Science (KIMS), Odisha state from 1st May to 20th October 2020. A total of 165 neonates born to SARS-CoV-2 infected mothers were enrolled. Real time polymerase chain reaction (RT PCR) testing was done in first 32 neonates in initial 24 hours of life. Results The clinical characteristics of 162 mothers & 165 neonates were analyzed. Mode of delivery was by caesarian section in most (n=103, 60%) cases. Three (3/32, 9.4%) inborn and 6 outborn neonates were SARS-CoV-2 positive. Thirty-eight (23%) babies needed neonatal intensive care. Clinical characteristics of neonates were meconium-stained amniotic fluid (MSAF, [23.63%]), prematurity (16.9%), respiratory distress (10.5%), moderate to severe hypoxic ischemic encephalopathy (3.6%), sepsis (7%) and hyperbilirubinemia (8.7%). Out of 138 stable babies kept on mother side and initiated breast feeding, none of them developed any signs and symptoms attributable to SARS-CoV-2. Five (3%) neonates died in COVID hospital of which one baby was SARS-CoV-2 positive. Conclusion There was an increased rate of incidences of hypoxic ischemic encephalopathy, meconium stained liquor and cesarean section delivery in COVID hospital. We found a possible vertical transmission in 9.4% cases. None of the neonates developed sign and symptoms of SARS-CoV-2 infection during rooming in and breast feeding. disease and later on 11 th March 2020, WHO declared this disease a global pandemic. 1 As of 4 th December 2020, the disease has affected over 60 million individuals, out of which over 45 million people recovered and 1.5 million were declared as deceased. According to various studies, it was found that the novel coronavirus infects all age groups including newborns and elderly, but there are a few groups which are more vulnerable to the infection. One such group is pregnant women. 2 The COVID-19 can severely affect the pregnant women. Current evidence on vertical transmission of SARS-CoV-2 and natural passive immunity among exposed newborns is emerging and posing a challenge for preventive interventions. Initial data by Vivanti et al; 2020 showed a transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester 3 , but current data demonstrate very rare maternal-fetal transmission, i.e., less than 1%. 4 Some studies showed elevated IgM antibodies to SARS-CoV-2 in neonates born to mothers with SARS-CoV-2 while others excluded the same. 5 Perinatal transmission to the neonates especially during breastfeeding is also unknown. 6 Moreover, infected newborns are mostly asymptomatic or present with mild clinical symptoms like shortness of breath, fever, or gastrointestinal symptoms. 7 There is limited information about the manifestation and outcome of neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive mothers from developing countries. Mothers with fetal distress, meconium-stained amniotic fluid (MSAF), post-dated pregnancy, severe pregnancy-induced hypertension (PIH), obstructed labor, and oligohydramnious were planned for cesarean section delivery. Neonates born to those mothers were tested within 24 hours of age by taking nasopharyngeal (NP) swab. If RT-PCR of the baby was positive, then the same schedule of testing was done for them as for the mother. For SARS-CoV-2 negative neonates who were kept at mother's side in the postnatal ward, repeat testing was not done and babies were discharged along with mothers after 10 days as per ICMR guidelines if they were asymptomatic. For neonates who were admitted to COVID NICU with RT-PCR negative, a repeat test was done on day 7 of life. If the test was negative, the baby was shifted to NICU in non-COVID hospital. RT PCR testing was done in the first 32 neonates in the existing facility at KIMS COVID Hospital. Six RT-PCR positive babies were received after 3 days of delivery from the outside hospitals. Asymptomatic neonates who were kept in the postnatal ward at the mother's side were allowed to room in with their mothers unless the mother is unwilling to keep the baby or she J o u r n a l P r e -p r o o f was critically unwell and therefore unable to take care of the baby. Infants who were roomed in were allowed to breastfeed with adequate droplet and contact precautions. 8 Babies were kept in a separate baby cot placed at least 6 feet away from the mother's bed. Mothers were advised to wear a mask when in close proximity to their babies and to perform proper hand hygiene practice while handling the baby or during breastfeeding. No visitors except healthcare persons with appropriate personal protective equipment were allowed to enter the COVID neonatal care unit. Expressed breast milk was given to neonates admitted to NICU as soon as it was available. Babies were discharged after they reached a weight of 1.8 kg and were hemodynamically stable taking full paladai feeds or shifted to other hospitals after they became SARS-CoV-2 negative if parents wished. Babies were followed up every week till 4 weeks by telephone about their wellbeing. Data regarding demographic, epidemiologic, and clinical features were collected from case records. Laboratory investigations like Chest X-ray, Clinical Breast Examination (CBE), Creactive Protein Test (CRP), Liver Function Test (LFT), blood culture sensitivity, electrolytes, urea, and creatinine were done. Data were analyzed using SPSS Version 20 (IBM Corp). Diagnosis of Hyaline Membrane Disease (HMD) was done on clinical and radiological findings and surfactants were given in severe HMD cases as per the European consensus guideline. 9 Hypotension was defined as mean arterial pressure <5 th centile of mean and it was considered significant when it required inotropic support. 10 Grading of hypoxic ischemic encephalopathy (HIE) was based on Sarnat staging. 11 Diagnosis of clinical sepsis was based upon positive sepsis screen markers like total leucocyte count, absolute neutrophil count, and C reactive protein along with positive blood culture growth done by Bac T Alert method. Necrotizing enterocolitis (NEC) was defined based on clinical and radiological evidence as per Bell's staging. 10 Chronic lung disease (CLD) was defined as the requirement of either oxygen or assisted ventilation beyond 36 weeks corrected age. when packed cell volume (PCV) was more than 70 and partial exchange transfusion was done when PCV was more than 75 or with symptoms like hypoglycemia, seizure, and feeding intolerance with PCV more than 70 ref. Blood sugar below 40 was defined as hypoglycemia which was managed as per national neonatology forum (NNF) protocol. 12 Diagnosis of neonatal hyperbilirubinemia requiring phototherapy was done based on American academy of pediatrics (AAP) guidelines. 13 Prolonged rupture of membrane (PROM) was taken as rupture of membrane for more than 24 hours. Of (Table 2) . Morbidities of babies admitted in NICU are described in Table 3 . The majority (n = 22, 58%) of these neonates were admitted for respiratory distress both in term and preterm infants. Surfactant was used in 4 (10.5%) cases. Assisted ventilation was done for 13 (34.2%) babies, out of which invasive ventilation was used in 8 cases. Out of 12 clinical sepsis, four (10.5%) babies were culture positive. Table 4 shows clinical characteristics of 9 positive neonates, of which 3 were from KIMS COVID hospital and 6 babies were referred cases from outside centers. Two neonates were asymptomatic. Sepsis was found in 4 cases and 2 neonates had HIE with seizure. Neonatal hyperbilirubinemia and shock were found in 2 cases each. One preterm outborn baby succumbed to sepsis and NEC on day 7 of life with NEC stage 3 and its complications. All other babies recovered and discharged with hemodynamically stable conditions. Details of COVID positive neonates are described in Table 4 . Five babies died during treatment, of which 3 babies had refractory seizures and 1 baby had hyaline membrane disease (HMD) and the other had culture positive sepsis (Table 5 ). The KIMS COVID hospital is the largest tertiary care center of Odisha state for SARS-CoV-2 positive pregnant mothers. There was an increased rate of cesarean section in COVID hospital. Also, the incidence of HIE and MSAF cases was more prevalent. We found a possible vertical transmission in 9.4% of cases, which is higher than other reported literature. 8 None of the neonates developed signs and symptoms of COVID-19 during rooming-in and breastfeeding. In this study, 29.7% of all neonates were low birth weight and 55.1% of them were secondary to prematurity. The national neonatal-perinatal database shows 30% of Indian neonates are of LBW (Low Birth Weight) and 40% are premature. 14 There is a rise in prematurity in SARS-CoV-2 positive pregnancy which might be due to an increased level of stress to the mothers. In this study, 60% of babies were delivered by a cesarean section, which is higher than the normal situation. In one study, the average cesarean section birth rate in India was around 17.2% with wide variation across states (range 5.8% -40.1%). However, the WHO threshold is 15%. 15 However, in a systematic review of 108 SARS-CoV-2 positive pregnancies, all outside India showed 92% were delivered by cesarean section and indication was fetal J o u r n a l P r e -p r o o f distress. 8 Meconium -stained liquor was found in 22% of deliveries in our study compared to 10% in pre-COVID era. 16 The fetal distress leading to MSAF during intrapartum period could not be explained solely by maternal COVID-19 infection, hence the need for further studies. The HIE incidence in our COVID hospital is 3.6%, compared to 1.5% in National Neonatal-Perinatal Database. This might be due to delay in getting RT PCR reports of mothers from ICMR as there was overload of testing samples and delayed referral to designated COVID hospital. Among 6 outborn SARS-CoV-2 positive neonates, 2 babies were asymptomatic. Cases 3 and symptomatic babies, 4 (11%) and 2 (6%) required mechanical ventilation and non-invasive respiratory support, respectively, but the authors could not exclude the need for respiratory support secondary to other neonatal morbidities. In this study, a total of 13/165 (7.6%) neonates required assisted ventilation, whereas 3/9 (33%) SARS-CoV-2 positive neonates required ventilator support. In the present study, the major morbidities of neonates of SARS-CoV-2 positive mothers were prematurity (16.9%), respiratory distress (10.5%), moderate to severe hypoxic ischemic encephalopathy (3.5%), sepsis (7%), and hyperbilirubinemia (8.7%). The neonatal morbidity pattern in COVID-19 hospital is similar to the Indian neonatal tertiary care burden as described in various studies. 19 -21 Five out of 38 (13.2%) neonates admitted to NICU died in the KIMS COVID hospital. Among the death cases 3 (60%) were due to severe hypoxic ischemic encephalopathy with multi-organ dysfunction, and 2 (40%) were due to extreme low birth weight and prematurityrelated complications, of which one baby (SARS-CoV-2 positive) was due to late onset of sepsis (Acinetobacter boumanni positive) with NEC stage 3 and multi-organ dysfunction. The neonatal mortality in the present study was higher compared to studies from overseas. 9, 18 High frequency oscillatory (HFO) ventilation, nitric oxide, cooling devices, bedside echocardiography, and invasive blood pressure monitoring were not available in COVID hospital NICU, which may be the cause of the high mortality in our study. Most of the neonates died as a result of pulmonary hemorrhage due to a lack of rescue strategies like HFO in COVID hospital. Though we had 165 neonates in the study group, we tested RT-PCR in 32 cases only due to hospital policy. However, these neonates are consecutive neonates out of symptomatic and asymptomatic SARS-COV-2 positive mothers reflecting the true presentation. We had not tested antibodies in these positive cases for confirmation of vertical transmission, which was a limitation. The neonates of SARS-CoV-2 positive mothers were not compared with non-COVID hospital neonates. However, we have compared the clinical presentation of these cases with existing NNPD and other literature. There is an increased incidence of meconium-stained liquor and cesarean section deliveries in SARS-COV-2 positive mothers. We found possible vertical transmission in 9.4% of cases. Hypoxic ischaemic encephalopathy is the leading cause of mortality in our COVID-19 NICU. Breastfeeding and rooming in of healthy neonates with SARS-COV-2 positive mothers with special precautions should be encouraged. The authors declare that they have no conflicts of interest to report. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Table 4 Clinical characteristics of SARS-CoV-2 positive neonates (n = 9). 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Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation National and regional estimates of term and preterm babies born small for gestational age in 138 lowincome and middle-income countries in 2010 Trends, regional variations, and socioeconomic disparities in cesarean births in India Risk factors for meconium aspiration in meconium stained amniotic fluid Vertical transmission of SARS CoV-2: a systematic review Coronavirus infection in neonates: a systematic review Morbidity and mortality patterns of neonates admitted to neonatal intensive care unit in tertiary care hospital Coronavirus disease 2019 in neonateswhat is known and what needs to be known Neonatal morbidity and mortality of sick newborns admitted in a teaching hospital of Uttarakhand The authors acknowledge the Kalinga Institute of Medical Sciences, Bhubaneswar; School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar; and KIIT Technology Business Incubator, Bhubaneswar for providing facilities and support. We appreciate all our lab colleagues for insightful discussions and advice. No funding was received to perform this study.