Outcomes from birth to 6 months of publicly insured infants born to mothers with severe acute respiratory syndrome coronavirus 2 infection in the United States

Abstract

Objectives

We evaluated inpatient management, transition to home, breastfeeding, growth, and clinical outcomes of infants born to mothers diagnosed with SARS-CoV-2 infection in pregnancy and followed in a Federally Qualified Health Center (FQHC), that serves a diverse and low-income patient population, from birth through 6 months of life.

Methods

Infants born between 4/3/20 and 7/26/20 at Prentice Women’s Hospital with mothers who received prenatal care at Erie Family Health Center (Erie), the second largest FQHC in Illinois, and had confirmed SARS-CoV-2 during pregnancy were included. Data were abstracted from delivery hospital admission and outpatient follow-up appointments between 4/8/20 and 2/4/21.

Results

Thirty-three infants met inclusion criteria. Average gestational age was 38.9 weeks (IQR 37.6–40.4), 3 (10%) were premature and 5 (15%) required NICU admission. Nearly all (97%) mothers expressed intent to breastfeed. Outpatient follow-up rates were similar to historical cohorts and 82% (23/28) of infants were vaccination compliant. Growth parameters showed normal distributions at all time points. At 6 months, any and exclusive breast milk feeding rates were lower compared to historic cohorts (18 vs. 36%, p<0.05, 0 vs. 21%, p<0.01). Three infants (10%) received development-related referrals, one carried an underlying genetic diagnosis. Outpatient visits were predominantly face-to-face with telemedicine use comprising only 6% of visits (11/182).

Conclusions

Longitudinal follow-up of 33 publicly insured infants born to mothers with SARS-CoV-2 infection in pregnancy followed in an FQHC showed high rates of follow-up and vaccination compliance, normal growth patterns and reassuring clinical status, and lower than expected rates of breastfeeding.

Introduction

The COVID-19 pandemic has caused devastating health and social impacts globally. Populations facing existing health inequities are disproportionately affected and simultaneously understudied [1], [2], [3], [4], [5], [6]. While certain direct impacts are starting to be uncovered, long-term, social, medical and developmental outcomes of publicly insured children, including neonates, in the United States and beyond are yet to be understood [7]. In April 2020, the American Academy of Pediatrics (AAP) recommended isolating mothers diagnosed with SARS-CoV-2 from their infants given the paucity of data on infant outcomes and the high infectivity of the virus in other populations [8, 9]. During this time period, hospitals and outpatient health care centers were advised to implement universal testing algorithms, screening questionnaires, visitor restrictions, and isolation of SARS-CoV-2 positive patients for the purposes of protecting staff and other patients, including their own newborns [10]. These actions presented unique challenges for healthcare providers and new families as safe newborn discharge and follow-up require assessment of the family as a unit.

Studies now show that vertical transmission of SARS-CoV-2 is uncommon, newborns can safely have contact with mother if precautions are taken, and infants exposed postnatally are unlikely to present with severe disease in the first few weeks of life [11], [12], [13], [14], [15], [16], [17], [18]. Outcomes beyond the neonatal period and data on the consequences of these initial recommendations, particularly for high-risk communities, are lacking [7, 19], [20], [21]. In this study, we sought to assess clinical outcomes of neonates born to mothers who received prenatal care at Erie Family Health Center (Erie), a Federally Qualified Health Center (FQHC) and were diagnosed with SARS-CoV-2 in pregnancy. In the United States, FQHC’s provide services including medical, dental, and behavioral healthcare to predominantly low-income patient populations to support healthier people, families, and communities. Erie serves over 80,000 patients per year, more than 90% of patients are low-income and 71% identify as LatinX.

Materials and methods

Data were collected from infants born between 4/3/20 and 7/26/20 at Prentice Women’s Hospital whose mothers received prenatal care at Erie, an FQHC in Chicago, IL and had a nasopharyngeal swab positive for SARS-CoV-2 during pregnancy. As part of the Northwestern Medicine campus, Prentice Women’s Hospital (PWH) instituted a universal testing algorithm for all inpatients starting 4/8/20. Data were abstracted from electronic medical records at the time of delivery and at outpatient infant follow-up appointments from Erie between 4/8/20 and 2/4/21. Inpatient data for mothers included the following: maternal age, ethnicity (self-reported), type of insurance, ICU admission, parity, timing of positive SARS-CoV-2 test in relation to delivery, symptoms of SARS-CoV-2 infection, intent to breastfeed, and mode of delivery. Data for infants included gestational age, sex, ethnicity (per parental report), NICU admission, APGAR scores, and results of Illinois Department of Public Health mandated newborn screens. Data from outpatient follow-up included caregiver accompanying infant, growth measurements, mode of feeding, health care concerns, attainment of developmental milestones, vaccination rates, and Ages and Stages Questionnaire (3rd edition), if available. SARS-CoV-2 RT-PCR testing at Erie was performed by AbbVie and LabCorp testing depending on site, through either oropharyngeal swab or anterior nares swab. Testing at PWH after 4/7/2020 was using the GeneXpert Dx Xpress SARS-CoV-2RT-PCR assay (Cepheid, Sunnyvale, CA).

Inpatient care

Inpatient clinical care of infants of mothers who tested positive for SARS-CoV-2 within 10 days of delivery during the study period included the following: infants were immediately isolated after delivery with the baby cared for in an isolation nursery or in the NICU if under 35 weeks, less than 2.0 kg, or needing special care. Lactation support including education on hand expression, frequency of pumping, and arrangement of breast pumps for home use was provided for isolated mothers intending to breast milk feed. Well infants of mothers who tested positive for SARS-CoV-2 more than 10 days prior to delivery and who had no additional positive tests were cared for with usual practices of rooming in and time in the nursery per parent request or medical need. Infants born within 14 days of a mother’s positive test were tested at 24 and 42–49 h of life and treated as persons under investigation (PUI’s) by staff while awaiting results. At the time, NICU visitation was only allowed if mothers showed laboratory confirmed evidence of clearance or if 40 days had passed from the original infection. These procedures took place during the entire study period when infants were born.

Transition to home

Infants SARS-CoV-2 positive women were initially discharged to an alternate caregiver, if available. The practice changed to discharge home with mother beginning May 18, 2020, as data on infant safety emerged. If the infant was discharged to a household with SARS-CoV-2 positive residents still in their quarantine period, caregivers were instructed on appropriate use of personal protective equipment (PPE) and hand hygiene, as per AAP recommendations [8]. Partner testing for SARS-CoV-2 was offered to facilitate newborn care and follow-up. Newborn follow-up was arranged after discharge at Erie with the intention that the infant would be accompanied by a presumably uninfected caregiver if the mother was still within her isolation period.

Outpatient follow-up Erie protocols

Erie staff and providers followed institutional COVID-19 protocols which included screening for SARS-CoV-2 exposure or symptoms in patients and the accompanying family member when making the appointment and again on arrival to the health center and use of PPE. Patients were seen at separate Erie sites depending on concern for exposure to SARS-CoV-2 (“urgent care sites” vs. “well sites”). Infants considered PUI’s due to exposure within the prior 14 days to a person known to be SARS-CoV-2 positive were seen with full PPE in a site where other patients with known or suspected SARS-CoV-2 infection were scheduled. Depending on symptoms, SARS-CoV-2 exposure, and family preference, some infants were seen in a fully in-person visit with the provider, some were seen in a hybrid model of part telehealth and part in person, and some were seen via telehealth (audio only or via video). Patients arriving at a “well site”, with symptoms or SARS-CoV-2 exposure were immediately isolated in an exam room and the history portion of the visit was routinely conducted over the phone before a brief in-person exam (Figure 1A).

Figure 1:

Outpatient visit types.

(A) COVID-19 algorithm for visit type. (B) Distribution of visit types.

Statistical methods

Categorical data were expressed as a number and percentage, and continuous data were expressed as a median with a range or interquartile. Fischer Exact test was used to compare breastfeeding rates of infants who roomed in with those who were separated, infants receiving any breast milk were combined with exclusive breast milk feeders. Chi-square test was used to compare dichotomous variables (Stata v16.0, College Station, TX). Breastfeeding rates are tracked as an internal quality measure and calculated by categorizing infants into 1) breast milk only, 2) formula only, or 3) both breast milk and formula groups. Data for SARS-CoV-2-exposed infants were compared to both 2020 and 2019 pre-pandemic rates, as 2020 data may have inadvertently included women with SARS-CoV-2 infection who were not tested, were diagnosed after delivery, or received a positive test outside the Erie or Northwestern system. The birth weight, length, and head circumference were expressed in Z-scores, using WHO growth charts as reference [22]. Ages and Stages Questionnaires were considered pass if parents completed all five portions and all scores were above cut-off setpoints in each area [23]. This study was approved by the Institutional Review Board at Northwestern University and by Erie’s Research Evaluation Committee.

Results

Thirty-three mothers received prenatal care at Erie, delivered at PWH, and tested positive for SARS-CoV-2 during pregnancy within the study period. Median age was 26.4 years (IQR 22.7–31.2), 33 (100%) self-identified as Latina, 33 (100%) were publicly insured, 10 (30%) were primiparous, and 5 (15%) had gestational diabetes. Thirteen (39%) tested positive greater than 14 days from delivery, 2 (6%) between 10 and 14 days and 18 (55%) at less than 10 days from delivery. Fifteen women (45%) had symptoms consistent with COVID-19 at the time of testing: 4 (12%) with fever, 7 (21%) with chills, 6 (18%) with cough, 7 (21%) with shortness of breath, 2 (6%) with sore throat, and 6 (18%) with anosmia. Nineteen mothers had partners tested, nine tested positive (47%) of which five were symptomatic (26%). No mothers required intensive care during COVID-19 infection or delivery hospitalization. Thirty-two (97%) expressed intent to breastfeed and all received lactation support (Table 1).

Table 1:

Summary of maternal and infant clinical characteristics.

Maternal characteristics		n=33 n (%)
Age at delivery, yearsa		26.4 (IQR 22.7–31.2)
Ethnicity (Latina)		33 (100%)
Maternal ICU admission		0 (0%)
Primaparous mother		10 (30%)
Gestational diabetes		5 (15%)
Public insurance		33 (100%)
Timing of maternal SARS-CoV-2 infection
	COVID positive test >14 days from delivery	13 (39%)
	COVID positive test 10–14 days from delivery	2 (6%)
	COVID positive test <10 days of delivery	18 (55%)
Symptomatic of COVID-19 at presentation		15 (45%)
Partner tested positive		9/19 (47%)
Intent to breastfeed		32 (97%)
Vaginal delivery		21 (64%)
Infant characteristics		n=33 (%)
Gestational age at delivery, weeksa		38.9 (IQR 37.6–40.4)
NICU admission		5 (15%)
Preterm birth, <37 weeks		3 (9%)
Length of stay in hospital, daysa		2 (IQR 2–3)
Sex, female		15 (45%)
APGARS (1, 5 min)b		8.15, 8.87 (1.5, 0.4)
Positive SARS-CoV-2 testing, n=22		0 (0%)
Passed newborn ABR		30 (90%)
Normal newborn screen		31 (94%)
Vaccinations up to date at 6 months		23/28 (82%)
Ages and stages passed		15/15 (100%)
Infant Z scoresa		(IQR)
n=33	Birth weight	−0.38 (−0.98–0.57)
	Birth OFC	−0.32 (−0.75–0.42)
	Birth length	0.48 (−0.73–1.38)
n=30	2 Month weight	−0.46 (-1.11–0.34)
	2 Month occipitofrontal circumference	0.60 (−0.35–1.76)
	2 Month length	−0.35 (−1.32–0.61)
n=29	4 Month weight	−0.15 (−0.55–0.52)
	4 Month occipitofrontal circumference	−0.13 (−0.66–0.34)
	4 Month length	−0.39 (−0.96–0.84)
n=28	6 Month weight	0.02 (−0.46–0.85)
	6 Month occipitofrontal circumference	0.00 (−0.90–1.14)
	6 Month length	−0.17 (−0.53–0.46)

^aMedian (IQR). ^bMean (SD).

Infant characteristics

Three infants (10%) were born preterm with gestational ages between 34 and 36 5/7 weeks and one of these infants required neonatal intensive care admission (NICU). Four additional infants (12%) required NICU admission for hypothermia, hypoglycemia, RDS, and sepsis evaluation. NICU length of stay ranged from 2 to 22 days. Of the five infants admitted to NICU, two had mothers who tested positive greater than 14 days, and three had mothers who tested positive less than 10 days prior to delivery. All five were isolated, tested for SARS-CoV-2, and had negative results at both 24 and 48 h of life.

Of the 28 infants admitted to the well-baby nursery, median length of stay was 2 days (IQR 2–3 days). Fifteen had mothers who tested positive within 10 days of delivery, two had mothers that tested positive between 10 and 14 days, and 11 had mothers that tested positive greater than 14 days. All infants whose mothers tested positive for SARS-CoV-2 within 10 days of delivery were separated. Virtual video visits were facilitated, and one mother declined virtual visits with her infant, citing she felt it would make separation harder. Infants admitted to the well-baby nursery whose mothers had a positive test within 14 days of delivery (n=17), were tested at 24 h and again at 42–48 h of life and all tests were negative.

Infant newborn screening results

All infants received eye ointment and vitamin K, passed congenital heart disease screening and had newborn and hearing screening prior to newborn hospital discharge. Newborn screen referral rates were similar to historic cohorts, with two infants (6%) referred for additional screening. One had serum amino acids sent which were normal and one required treatment for congenital hypothyroidism. Three infants (10%) referred unilaterally on hearing screening. One infant passed formal audiology evaluation, another had equivocal results and continues to be followed by audiology, and one was lost to follow-up.

Discharge disposition

Of the 15 infants separated from their mothers in the hospital, two were lost to follow-up, seven were discharged to alternate healthy caregivers, six were discharged home to a household, either with mother or with caregiver, where mother had not completed 14 days of quarantine. Alternative caregivers included the following: five fathers, seven grandparents or aunts. One household had no caregivers except mother, who had not completed quarantine.

Outpatient visits

Newborn follow-up, 2 months, 4 months, and 6 months visit information was available for 32 (97%), 30 (90%), 29 (88%), and 28 (85%) infants respectively. Most initial newborn outpatient visits were in-person (30/32, 94%) on an average day of life 5. Of the two that occurred via telehealth, one was a premature infant with a NICU stay of 20 days. Twelve infants were brought to in-person visits without mother due to quarantine (five by fathers, seven by grandmother or aunt). One mother brought infant to follow-up despite quarantine not being completed. Of 182 total infant outpatient medical visits during the study period, 150 (82%) were face to face, 19 (10%) were hybrid with the patient in an exam room, communication by phone with the provider, followed by a shortened physical exam, and 11 (6%) were telemedicine (Figure 1B).

Breastfeeding and infant growth

Fifteen infants were receiving any breastmilk at initial hospital follow-up, with three exclusively breastfed. Separated infants were less likely than those that roomed in to receive breast milk at follow-up (71% vs. 28%, p<0.05), but this change was not sustained at subsequent visits (46% vs. 35% at 2 months, p=0.71). Erie’s breast milk feeding rates did not change from 2019 to 2020 (Figure 2). Compared to historic, pre-pandemic 2019 cohort, any and exclusive breastfeeding rates were lower at each time point but only showed statistically significance at 6 months. Average weight loss from birth of the 30 live visits was 4.9% (SD 3.0%, follow-up range DOL 3–7). At birth, 2-, 4-, and 6-months follow-up, Z-scores and growth velocity showed normal distributions for weight, length, and head circumference (Figure 3).

Figure 2:

Breastfeeding rates of SARS-CoV-2 exposed infants compared to cohorts from 2019 to 2020.

(A) Exclusive breastfeeding rates and any breastfeeding rates at 2, 4, and 6 months among FQHC mother-infant dyads. Data shown are from 2019, 2020, and our cohort of 30 dyads affected by SARS-CoV-2 infection during pregnancy. (B) Table of n (%) and p-values from Chi-square test (Stata v16.0, College Station, TX).

Figure 3:

Growth parameters distribution by Z-score.

Six-month follow-up was available for 28 infants: one infant did not follow-up due to hospital admission and four infants were lost to follow-up. All were seen for live visits and 23/28 (82%) were up to date on recommended vaccines. At the time of chart abstraction, Ages and Stages questionnaires results were available for 15 infants and in all cases the child’s development was on schedule. Three received development-related referrals: one was referred to speech therapy for progressive dysphagia and ultimately required a gastrostomy tube, one was referred for neurology and genetics consultation and diagnosed with Klinefelter, and one was referred for neurology consultation for microcephaly which was thought to be familial. Of note, during the study period, the infant hospitalized at 6 months follow-up died at 7 months of age of hepatic failure due to a mutation in tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase.

Discussion

Assessment of successful adaptation to extrauterine life and transition from birth hospitalization to outpatient care are essential parts of newborn medicine, even more so amidst the coronavirus pandemic. Criteria for safe discharge includes establishment of proper feeding, appropriate thermoregulation, completion of necessary newborn screens, evaluation of social determinants of health, parental education, and arrangement of follow-up at 3–5 days of life which can be especially challenging in communities where access to care is limited [24], [25], [26]. While initial guidelines recommending isolation of mothers, treatment of infants as PUI’s, and quarantine in the first few weeks of life posed challenges to discharge planning and transition to outpatient care, our cohort of infants exposed to SARS-CoV-2 perinatally showed a high follow-up rate for wellness visits at Erie, compliance with recommendations for vaccinations, and reassuring growth patterns and clinical outcomes. Partner testing did not always facilitate discharge planning, as some partners were not available for testing, and some declined. When partners tested positive, an additional caregiver had to be identified and these additional caregivers could not always be tested, lending additional complexity to the discharge planning process.

FQHCs provide services including medical, dental, and behavioral healthcare to predominantly low-income patient populations in the United States to support healthier people, families, and communities [27], [28], [29], [30]. FQHC’s serve 1 in 11 people across the United States and have been at the forefront of delivering care throughout the COVID-19 pandemic [31], [32], [33], [34]. In this small study, both the population served, and the health care providers of Erie adapted readily to uncertain times to facilitate follow-up. Extended family often brought infants to appointments when parents were under quarantine and outpatient providers adapted to a new model for patient care including standardized questionnaires and utilizing telemedicine when needed. Although not an outcome of this study, the approach at Erie resulted in no known transmissions to healthcare workers from patients despite primarily face to face visits for infant well child checks.

While data on immediate perinatal outcomes of infants born to mothers with SARS-CoV-2 infection has been reassuring, little is known about long-term growth and development [17, 18, 35, 36]. The growth parameters of the infants of this cohort showed normal distributions at all time points and suggest a normal trajectory. In addition, available developmental screening showed most infants meeting milestones. Infants referred for therapies or further investigation appeared unrelated to SARS-CoV-2 exposure.

Despite maternal intent, lactation support, access to adequate follow-up for well child visits, and infants being clinically well, this cohort demonstrated lower than expected duration of breast milk feeding compared to historic cohorts. Our institution followed the initial AAP recommendations of isolating newly diagnosed mothers and have since adopted policies encouraging rooming in with precautions. While mothers who roomed with their infants had higher breast milk feeding rates at newborn follow-up, the increase was not sustained. Though disparities have been well-documented in publicly insured communities, Erie provides lactation support both pre and postnatally and has high breastfeeding rates compared to national averages [37], [38], [39], [40]. These findings are concerning and suggest that special attention is needed for this population, as ensuring successful lactation is the first line of defense during times of crises [41, 42].

Our study examines an important, high-risk population of families, but has some notable limitations. The sample size is small, some infants were lost to follow-up, and developmental information is incomplete. This study was conducted during the initial wave of infections in the United States. Since this study, many new variants and waves of the SARS-CoV-2 virus have emerged, and findings may now be different for mother-infant dyads in which birth occurred during infections with different variant virus strands. In addition, all families were of LatinX ethnicity. Though communities of color are disproportionately affected by the pandemic, ethnicity was not part of the study design, and our findings may not be applicable to more diverse and vulnerable populations throughout the world. Finally, as the health care system in the United States can vary depending on the patient’s location and insurance status, these study results may be less applicable to other health systems internationally.

FQHCs have been and continue to be at the forefront of providing care to vulnerable communities during the COVID-19 pandemic in the United States. Our study highlights that this population can provide valuable insights into the long-term outcomes of this pandemic for diverse and underserved populations throughout the world. Further study is needed on the transition of new mothers and families affected by SARS-CoV-2 in high-risk populations, and it is critical to include and evaluate outcomes of families who seek care at FQHC’s in the United States, as these populations have long been underrepresented in medical research.