Maternal and Newborn Hospital Outcomes of Perinatal SARS-CoV-2 Infection: A National Registry.

OBJECTIVES: The American Academy of Pediatrics National Registry for the Surveillance and Epidemiology of Perinatal coronavirus disease 2019 (COVID-19) (NPC-19) was developed to provide information on the effects of perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: National Registry for the Surveillance and Epidemiology of Perinatal COVID-19 participating centers entered maternal and newborn data for pregnant persons who tested positive for SARS-CoV-2 infection between 14 days before and 10 days after delivery. Incidence of and morbidities associated with maternal and newborn SARS-CoV-2 infection were assessed. RESULTS: From April 6, 2020 to March 19, 2021, 242 centers in the United States centers reported data for 7524 pregnant persons; at the time of delivery, 78.1% of these persons were asymptomatic, 18.2% were symptomatic but not hospitalized specifically for COVID-19, 3.4% were hospitalized for COVID-19 treatment, and 18 (0.2%) died in the hospital of COVID-related complications. Among 7648 newborns, 6486 (84.8%) were tested for SARS-CoV-2, and 144 (2.2%) were positive; the highest rate of newborn infection was observed when mothers first tested positive in the immediate postpartum period (17 of 125, 13.6%). No newborn deaths were attributable to SARS-CoV-2 infection. Overall, 15.6% of newborns were preterm: among tested newborns, 30.1% of polymerase chain reaction-positive and 16.2% of polymerase chain reaction-negative were born preterm (P < .001). Need for mechanical ventilation did not differ by newborn SARS-CoV-2 test result, but those with positive tests were more likely to be admitted to a NICU. CONCLUSIONS: Early in the pandemic, SARS-CoV-2 infection was acquired by newborns at variable rates and without apparent short-term effects. During a period that preceded widespread availability of vaccines, we observed higher than expected numbers of preterm births and maternal in-hospital deaths.

Diagnostic Performance and Patient Outcomes With C-Reactive Protein Use in Early-Onset Sepsis Evaluations.

OBJECTIVES: To determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP. STUDY DESIGN: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units. CRP was used routinely in early-onset sepsis evaluations during 2009-2014; this period was used to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed early-onset sepsis. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014. RESULTS: From 2009 to 2014, 10 134 infants were admitted; 9103 (89.8%) had CRP and 7549 (74.5%) had blood culture obtained within 3 days of birth. CRP obtained ±4 hours from blood culture had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, we observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period. Rate and timing of early-onset sepsis detection, transfer to a greater level of care, and in-hospital mortality were not different between periods. CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in early-onset sepsis. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.

Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly.

Antibiotics are administered near-universally to very low birth weight (VLBW) infants after birth for suspected early-onset sepsis (EOS). We previously identified a phenotypic group of VLBW infants, referred to as low-risk for EOS (LRE), whose risk of EOS is low enough to avoid routine antibiotic initiation. In this cohort study, we compared 18 such infants with 30 infants categorized as non-LRE to determine if the lower risk of pathogen transmission at birth is accompanied by differences in microbiome acquisition and development. We did shotgun metagenomic sequencing of 361 fecal samples obtained serially. LRE infants had a higher human-to-bacterial DNA ratio than non-LRE infants in fecal samples on days 1-3 after birth, confirming lower bacterial acquisition among LRE infants. The microbial diversity and composition in samples from days 4-7 differed between the groups with a predominance of Staphylococcus epidermidis in LRE infants and Enterobacteriaceae sp. in non-LRE infants. Compositional differences were congruent with the distribution of virulence factors and antibiotic resistant genes. After the first week, the overall composition was similar, but changes in relative abundance for several taxa with increasing age differed between groups. Of the nine late-onset bacteremia episodes, eight occurred in non-LRE infants. Species isolated from the blood culture was detected in the pre-antibiotic fecal samples of the infant for all episodes, though these species were also found in infants without bacteremia. In conclusion, LRE infants present a distinct pattern of microbiome development that is aligned with their low risk for EOS. Further investigation to determine the impact of these differences on later outcomes such as late-onset bacteremia is warranted.

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection.

Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy. Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2. Design, Setting, and Participants: This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads. Exposures: SARS-CoV-2 infection vs COVID-19 vaccination. Main Outcomes and Measures: IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines. Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination. Conclusions and Relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

Breast Milk and Saliva for Postnatal Cyto†megalovirus Screening among Very Low Birth Weight Infants.

BACKGROUND: The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed. OBJECTIVE: Determine whether mother's milk and infant saliva can be used to reliably identify maternal cytomegalovirus (CMV) serostatus and detect infant pCMV acquisition. METHODS: This was a single-center, prospective cohort study of VLBW infants, and their mothers, born between 2017 and 2020. Maternal milk samples were tested for CMV immunoglobulin G (IgG) using a CMV glycoprotein B binding enzyme-linked immunosorbent assay and the results were compared with maternal serum CMV IgG results. Biweekly paired saliva and urine samples were collected from infants born to mothers with positive or unknown CMV serostatus. Saliva samples were tested for CMV DNA by quantitative real-time polymerase chain reaction (PCR) and compared with urine CMV qualitative PCR results obtained from a clinical laboratory. RESULTS: Among 108 infants without congenital CMV included in the study, 10 (9%) acquired pCMV. Both milk and blood CMV serology results were available for 70 mothers. Maternal milk antibody testing had a sensitivity of 97.2% (95% CI: 85.5-99.9%) and specificity of 91.2% (95% CI: 76.3-98.1%) in establishing CMV serostatus. Paired serially collected saliva and urine samples (n = 203) were available for 66 infants. Saliva PCR had a sensitivity of 30.0% (95% CI: 6.7-65.2%) and specificity of 92.7% (95% CI: 88.1-96.0%) in detecting pCMV acquisition. CONCLUSIONS: Maternal breast milk is a reliable alternative sample to determine CMV serostatus. Serial testing of infant saliva was not adequately sensitive for identifying pCMV acquisition in preterm infants.

Perinatal COVID-19 maternal and neonatal outcomes at two academic birth hospitals.

OBJECTIVE: Describe 1-month outcomes among newborns of persons with perinatal COVID-19. STUDY DESIGN: Prospective observational study of pregnant persons who tested positive for SARS-CoV-2 between 14 days before and 3 days after delivery and their newborns, from 3/2020 to 3/2021 at two urban high-risk academic hospitals. Phone interviews were conducted to determine 1-month newborn outcomes. RESULTS: Among 9748 pregnant persons, 209 (2.1%) tested positive for perinatal SARS-CoV-2. Symptomatically infected persons were more likely to have a preterm delivery due to worsening maternal condition and their newborns were more likely to test positive for SARS-CoV-2 compared with asymptomatic persons. Six of 191 (3.1%) infants tested were positive for SARS-CoV-2; none had attributable illness before discharge. Of 169 eligible families, 132 (78.1%) participated in post-discharge interviews; none reported their newborn tested positive for SARS-CoV-2 by 1 month of age. CONCLUSION: Symptomatic perinatal COVID-19 had a substantial effect on maternal health but no apparent short-term effect on newborns.

Neighborhood Characteristics and Racial Disparities in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seropositivity in Pregnancy.

OBJECTIVE: To quantify the extent to which neighborhood characteristics contribute to racial and ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity in pregnancy. METHODS: This cohort study included pregnant patients who presented for childbirth at two hospitals in Philadelphia, Pennsylvania from April 13 to December 31, 2020. Seropositivity for SARS-CoV-2 was determined by measuring immunoglobulin G and immunoglobulin M antibodies by enzyme-linked immunosorbent assay in discarded maternal serum samples obtained for clinical purposes. Race and ethnicity were self-reported and abstracted from medical records. Patients' residential addresses were geocoded to obtain three Census tract variables: community deprivation, racial segregation (Index of Concentration at the Extremes), and crowding. Multivariable mixed effects logistic regression models and causal mediation analyses were used to quantify the extent to which neighborhood variables may explain racial and ethnic disparities in seropositivity. RESULTS: Among 5,991 pregnant patients, 562 (9.4%) were seropositive for SARS-CoV-2. Higher seropositivity rates were observed among Hispanic (19.3%, 104/538) and Black (14.0%, 373/2,658) patients, compared with Asian (3.2%, 13/406) patients, White (2.7%, 57/2,133) patients, and patients of another race or ethnicity (5.9%, 15/256) (P<.001). In adjusted models, per SD increase, deprivation (adjusted odds ratio [aOR] 1.16, 95% CI 1.02-1.32) and crowding (aOR 1.15, 95% CI 1.05-1.26) were associated with seropositivity, but segregation was not (aOR 0.90, 95% CI 0.78-1.04). Mediation analyses revealed that crowded housing may explain 6.7% (95% CI 2.0-14.7%) of the Hispanic-White disparity and that neighborhood deprivation may explain 10.2% (95% CI 0.5-21.1%) of the Black-White disparity. CONCLUSION: Neighborhood deprivation and crowding were associated with SARS-CoV-2 seropositivity in pregnancy in the prevaccination era and may partially explain high rates of SARS-CoV-2 seropositivity among Black and Hispanic patients. Investing in structural neighborhood improvements may reduce inequities in viral transmission.

Early childhood antibiotic utilization for infants discharged from the neonatal intensive care unit.

OBJECTIVE: To determine antibiotic utilization for NICU infants, as compared to non-NICU infants, in the first 3 years after birth hospital discharge. STUDY DESIGN: Retrospective observational study using data from Medicaid Analytic Extract including 667 541 newborns discharged from 2007-2011. Associations between NICU admission and antibiotic prescription were assessed using regression models, adjusting for confounders, and stratified by gestational age and birth weight. RESULTS: 596 999 infants (89.4%) received ≥1 antibiotic, with a median of 4 prescriptions per 3 person-years (IQR 2-8). Prescribed antibiotics and associated indication were similar between groups. Compared to non-NICU infants (N = 586 227), NICU infants (N = 81 314) received more antibiotic prescriptions (adjusted incidence rate ratio 1.08, 95% confidence interval [CI] (1.08,1.08)). Similar results were observed in all NICU subgroups. CONCLUSIONS: Antibiotic utilization in early childhood was higher among infants discharged from NICUs compared to non-NICU infants.

Time to positivity of blood cultures in neonatal late-onset bacteraemia.

OBJECTIVE: To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours. DESIGN: Retrospective cohort study. SETTING: 16 birth centres in two healthcare systems. PATIENTS: Infants with positive blood cultures obtained >72 hours after birth. OUTCOME: The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours. RESULTS: Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia. CONCLUSIONS: Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.

Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis.

BACKGROUND AND OBJECTIVES: Multiple strategies are used to identify newborn infants at high risk of culture-confirmed early-onset sepsis (EOS). Delivery characteristics have been used to identify preterm infants at lowest risk of infection to guide initiation of empirical antibiotics. Our objectives were to identify term and preterm infants at lowest risk of EOS using delivery characteristics and to determine antibiotic use among them. METHODS: This was a retrospective cohort study of term and preterm infants born January 1, 2009 to December 31, 2014, with blood culture with or without cerebrospinal fluid culture obtained ≤72 hours after birth. Criteria for determining low EOS risk included: cesarean delivery, without labor or membrane rupture before delivery, and no antepartum concern for intraamniotic infection or nonreassuring fetal status. We determined the association between these characteristics, incidence of EOS, and antibiotic duration among infants without EOS. RESULTS: Among 53 575 births, 7549 infants (14.1%) were evaluated and 41 (0.5%) of those evaluated had EOS. Low-risk delivery characteristics were present for 1121 (14.8%) evaluated infants, and none had EOS. Whereas antibiotics were initiated in a lower proportion of these infants (80.4% vs 91.0%, P < .001), duration of antibiotics administered to infants born with and without low-risk characteristics was not different (adjusted difference 0.6 hours, 95% CI [-3.8, 5.1]). CONCLUSIONS: Risk of EOS among infants with low-risk delivery characteristics is extremely low. Despite this, a substantial proportion of these infants are administered antibiotics. Delivery characteristics should inform empirical antibiotic management decisions among infants born at all gestational ages.

Improving Compliance With Revised Newborn Hepatitis B Vaccination Policy.

BACKGROUND: In September 2017, the American Academy of Pediatrics issued guidance recommending hepatitis B vaccine be administered to well newborns with birth weight ≥2000 g within 24 hours after birth. At that time, ∼85% of well newborns were vaccinated before discharge at our center; however, only 35% were vaccinated within 24 hours after birth. Our aim was to vaccinate 70% of eligible newborns within 24 hours after birth by June 2018 while maintaining the overall rate of vaccination. METHODS: A multidisciplinary improvement team analyzed existing vaccine administration processes in the well-newborn nursery. From October 2017 to January 2018, changes were made to activation of vaccine orders and to obtaining and documenting the consent processes. Vaccine administration was bundled with routine care given ≤24 hours after birth, and parent scripting was changed from offering vaccine as an option to stating it as a recommendation. From November 2016 to June 2019, we determined the overall rate and timing of vaccination using statistical process control methods. RESULTS: Among 10 887 eligible infants, the proportion administered hepatitis B vaccine ≤24 hours after birth increased from 35.5% to 78.8% after process changes with special-cause variation on process control charts. Proportion of infants receiving vaccine any time before discharge also increased from 86.5% to 92.3%. CONCLUSIONS: Specific process changes allowed our birth center to comply with the recommended timing for hepatitis B vaccination of ≤24 hours after birth among eligible newborns.

Intrapartum group B Streptococcal prophylaxis and childhood weight gain.

OBJECTIVE: To determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP). DESIGN: Retrospective cohort study of 13 804 infants. SETTING: Two perinatal centres and a primary paediatric care network in Philadelphia. PARTICIPANTS: Term infants born 2007-2012, followed longitudinally from birth to 5 years of age. EXPOSURES: GBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure. OUTCOMES: Difference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates. RESULTS: GBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children. CONCLUSION: GBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies.

Intrapartum Group B Streptococcal Prophylaxis and Childhood Allergic Disorders.

OBJECTIVES: To determine if maternal intrapartum group B Streptococcus (GBS) antibiotic prophylaxis is associated with increased risk of childhood asthma, eczema, food allergy, or allergic rhinitis. METHODS: Retrospective cohort study of 14 046 children. GBS prophylaxis was defined as administration of intravenous penicillin, ampicillin, cefazolin, clindamycin, or vancomycin to the mother, ≥4 hours before delivery. Composite primary outcome was asthma, eczema, or food allergy diagnosis within 5 years of age, identified by diagnosis codes and appropriate medication prescription. Allergic rhinitis was defined by using diagnostic codes only and analyzed as a separate outcome. Analysis was a priori stratified by delivery mode and conducted by using Cox proportional hazards model adjusted for multiple confounders and covariates. Secondary analyses, restricted to children retained in cohort at 5 years' age, were conducted by using multivariate logistic regression. RESULTS: GBS prophylaxis was not associated with increased incidence of composite outcome among infants delivered vaginally (hazard ratio: 1.13, 95% confidence interval [CI]: 0.95-1.33) or by cesarean delivery (hazard ratio: 1.08, 95% CI: 0.88-1.32). At 5 years of age, among 10 404 children retained in the study, GBS prophylaxis was not associated with the composite outcome in vaginal (odds ratio: 1.21, 95% CI: 0.96-1.52) or cesarean delivery (odds ratio: 1.17, 95% CI: 0.88-1.56) cohorts. Outcomes of asthma, eczema, food allergy, separately, and allergic rhinitis were also not associated with GBS prophylaxis. CONCLUSIONS: Intrapartum GBS prophylaxis was not associated with subsequent diagnosis of asthma, eczema, food allergy, or allergic rhinitis in the first 5 years of age.

Neonatal blood culture inoculant volume: feasibility and challenges.

BACKGROUND: Clinicians often express concerns about poor sensitivity of blood cultures in neonates resulting from inadequate inoculant volumes. Our objective was to determine the inoculant volume sent for neonatal sepsis evaluations and identify areas of improvement. METHODS: Single-center prospective observational study of infants undergoing sepsis evaluation. Blood volume was determined by clinician documentation over 21 months, and additionally by weighing culture bottles during 12 months. Adequate volume was defined as ≥1 mL total inoculant per evaluation. For first-time evaluations, local guidelines recommend sending an aerobic-anaerobic pair with 1 mL inoculant in each. RESULTS: There were 987 evaluations in 788 infants. Clinicians reported ≥1 mL total inoculant in 96.9% evaluations. Among 544 evaluations where bottles were weighed, 93.4% had ≥1 mL total inoculant. Very low birth weight infants undergoing evaluations >7 days after birth had the highest proportion of inadequate inoculants (14.4%). Only 3/544 evaluations and 26/1011 bottles had total inoculant <0.5 mL. Ninety evaluations had <1 mL in both aerobic and anaerobic bottles despite a total inoculant volume that allowed inoculation of ≥1 mL in one of the bottles. CONCLUSIONS: Obtaining recommended inoculant volumes is feasible in majority of neonates. Measuring inoculant volumes can focus improvement efforts and improve test reliability. IMPACT: Clinicians express concern about the unreliability of neonatal blood cultures because of inadequate inoculant volume. We investigated over 900 evaluations and found >90% of evaluations have ≥1 mL inoculant. Monitoring adequacy of blood culture technique can identify areas of improvement and may allay concerns about blood culture reliability. Current recommendations for adequate inoculant volume for blood cultures are met in a majority of neonates. Areas of improvement include preterm late-onset sepsis evaluations and distribution techniques during inoculation.

Updated Guidance: Prevention and Management of Perinatal Group B Streptococcus Infection.

Group B Streptococcus (GBS) remains the most common cause of neonatal early-onset sepsis among term infants and a major cause of late-onset sepsis among both term and preterm infants. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists published separate but aligned guidelines in 2019 and 2020 for the prevention and management of perinatal GBS disease. Together, these replace prior consensus guidelines provided by the Centers for Disease Control and Prevention. Maternal intrapartum antibiotic prophylaxis based on antenatal screening for GBS colonization remains the primary recommended approach to prevent perinatal GBS disease, though the optimal window for screening is changed to 36 0/7 to 37 6/7 weeks of gestation rather than beginning at 35 0/7 weeks' gestation. Penicillin, ampicillin, or cefazolin are recommended for prophylaxis, with clindamycin and vancomycin reserved for cases of significant maternal penicillin allergy. Pregnant women with a history of penicillin allergy are now recommended to undergo skin testing, because confirmation of or delabeling from a penicillin allergy can provide both short- and long-term health benefits. Aligned with the American Academy of Pediatrics recommendations for evaluating newborns for all causes of early-onset sepsis, separate consideration should be given to infants born at less than 35 weeks' and more than or equal to 35 weeks' gestation when performing GBS risk assessment. Empiric antibiotics are recommended for infants at high risk for GBS early-onset disease. Although intrapartum antibiotic prophylaxis is effective in preventing GBS early-onset disease, currently there is no approach for the prevention of GBS late-onset disease.

Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios.

Importance: Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies. Objective: To assess the association between maternal and neonatal SARS-CoV-2-specific antibody concentrations. Design, Setting, and Participants: This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads. Exposures: SARS-CoV-2. Main Outcomes and Measures: IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data. Results: The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery. Conclusions and Relevance: In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

Delivery-based criteria for empiric antibiotic administration among preterm infants.

OBJECTIVE: Determine impact of using delivery criteria to initiate antibiotics among very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. STUDY DESIGN: Single site cohort study from 01/01/2009 to 01/31/2020. After 04/2017, infants delivered by Cesarean section, without labor or membrane rupture were categorized as low-risk for early-onset infection and managed without empiric antibiotics. We determined effect of this guideline by pre-post, and interrupted time-series analyses. RESULTS: After 04/2017, antibiotic initiation ≤3 days decreased among low-risk VLBW (62% vs. 13%, p < 0.001) and low-risk ELBW (88% vs. 21%, p < 0.001) infants. In time series analysis, guideline was associated with decreased initiation among low-risk ELBW infants. In contrast, low-risk VLBW infants demonstrated decreased antibiotic initiation throughout study period. Incidence of confirmed infection, death, or transfer ≤7 days age was unchanged. CONCLUSION: Delivery criteria may be used to optimize early antibiotic initiation among preterm infants without short-term increase in adverse outcomes.