Comparison of neonatal outcomes from mothers with and without COVID-19 in a tertiary referral hospital in Jakarta,Indonesia,neonatal COVID-19 in Indonesia

Abstract

Background

Coronavirus disease 2019 (COVID-19) in pregnant women and neonates may adversely affect neonatal outcome, but literature remains limited.

Methods

This is a retrospective analysis of all infants born to mothers with and without COVID-19 at an Indonesian national referral hospital between March and September 2020.

Results

A total of 393 neonates were delivered by 389 mothers, of whom 204 (52.4%) had COVID-19. Symptomatic and asymptomatic mothers with COVID-19 had similar seropositivity rates (53.6% vs 69.8%, p = 0.090). Neonates born to noninfected mothers were more likely to experience asphyxia at minute 1 of life (p = 0.005), to be diagnosed with TTN (p = 0.048) and sepsis (p = 0.022) and to require resuscitation (p = 0.008) than those born to infected mothers. Nine (2.4%) out of 377 tested infants were positive for SARS-CoV-2, of whom 4 had noninfected mothers. Neonates of mothers with symptomatic COVID-19 were less likely to be seropositive (30.0% vs 52.4%, p = 0.024) and more likely to acquire COVID-19 (p = 0.026) than those born to asymptomatically infected mothers.

Conclusion

This study suggests that maternal COVID-19, particularly when occurring in late pregnancy, was not associated with an increase in acute neonatal complications.

Keywords

COVID-19 neonates pregnant women SARS-CoV-2 serology

Introduction

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents a threat to pregnant women and neonates. Respiratory viral infection poses a higher risk to neonates due to their dampened innate and adaptive immune responses and relative immunologic naivety.¹ Indeed, children under five, particularly infants, are more likely to develop severe disease, require ICU admission and die from COVID-19 than older children.^2–4 Due to these concerns, early interim guidelines considered conservative measures such as separating infants from and discouraging breastfeeding by mothers with confirmed COVID-19 to prevent vertical transmission.^5–7

While these recommendations have since been rescinded, neonatal COVID-19 remains poorly understood. The number of reported neonatal COVID-19 cases are still limited. Some studies have linked neonatal SARS-CoV-2 infection to Cesarean delivery⁸ and rooming-in Ref. 9. However, most studies^10–15 only examined incident neonatal infection among infants born to infected mothers. Studies reporting concurrent virological and serological testing for neonates are also lacking. The present study aims to determine the characteristics of infants born to mothers with and without COVID-19, particularly the incidence of neonatal COVID-19, neonatal outcomes and seropositivity against COVID-19.

Methods

Study design and population

This study was conducted at Persahabatan General Hospital, a Type A (tertiary referral) hospital located in East Jakarta. In the mid of the overwhelming pandemic situation and the unpreparedness of the facilities in surrounding hospitals for the infectious disease COVID-19, Persahabatan Hospital, as a national respiratory referral center, quickly positioned itself as one of the national referral hospitals for COVID-19 cases.

Ethical approval was obtained from the Health Research Ethics Committee, Persahabatan General Hospital with the number 64/KEPK-RSUPP/6/2020. Written informed consent was obtained from all subjects before the study.

All lives neonates born during the period from mid-March to early September 2020 were included in the inclusion criteria. These neonates were born to pregnant women referred by healthcare facilities surrounding Persahabatan Hospital, with documented positive COVID-19 results, either through antigen testing or RT-PCR. During their care at Persahabatan Hospital, they underwent repeat COVID-19 confirmation testing using the RT-PCR method both at birth and later during their care. Neonates and their mothers were included in this study.

Maternal and neonatal COVID-19 were defined as having at least one positive RT-PCR on nasopharyngeal swab specimen. Maternal and neonatal seropositivity were defined as detection of anti-SARS-CoV-2 immunoglobulin G (IgG) by electrochemiluminescence immunoassay (Roche Diagnostics) performed upon admission. Maternal RT-PCR and serology were conducted upon hospital admission. Neonatal RT-PCR was typically performed within the first 48 h of life, although a few were tested on day 2 or later. Neonatal serology was performed once during admission, generally within the first 24–48 h. During the study period, rooming-in was not practiced due to the limited number of rooms; after delivery, mothers were transferred to isolation rooms or non-COVID-19 wards and infants to the perinatology unit. Due to concerns of SARS-CoV-2 transmission through breastmilk at the time, all neonates received formula feeding during hospitalization.

Data were collected from medical records. Obstetric complications, if present, were recorded from the patient’s discharge form. Neonatal asphyxia was defined as an Apgar score <7. Chest X-rays were obtained for infants as indicated by respiratory distress. Adverse neonatal events (e.g., sepsis, pneumonia, respiratory distress syndrome [RDS], meconium aspiration syndrome [MAS], transient tachypnea of the newborn [TTN], and pneumothorax) were diagnosed by the attending neonatologist.

Statistical analysis

This study aims to compare neonatal outcomes between two groups: neonates born to mothers with confirmed COVID-19 and those born to mothers without COVID-19. The primary outcomes of interest are non-numeric categorical variables. To ensure adequate statistical power to detect clinically meaningful differences in these rare outcomes, a sample size calculation was performed based on a two-group comparison of proportions. Assumptions for the power analysis; proportion of neonatal infection (in COVID-negative group (P₁) is 5% and proportion of neonatal infection in COVID-positive group (P₂) is 15%. The estimated minimum sample size required is approximately 134 neonates per group, resulting in a total of 268 neonates. This sample size is sufficient to detect a 10% absolute difference in the rate of neonatal infections between the two groups with 80% power and a 5% significance level. Categorical variables were analyzed using Chi-squared or Fisher’s exact test. Continuous variables were analyzed using Mann-Whitney U test. Pairwise deletion was performed with regards to missing data to preserve more information. All statistical analyses were performed using SPSS version 26.0 (IBM, Armonk).

Result

A total of 423 pregnant women were referred to Persahabatan Hospital during the study period and 389 had live births (Figure 1). Of these, 204 (52.4%) had confirmed COVID-19 and 185 (47.6%) did not. The infection was detected either when the pregnant woman developed symptoms or during antenatal check-ups in the third trimester, close to delivery. During the acute phase of the pandemic, it is highly unlikely that COVID-19 infection occurred earlier in the pregnancy.

The median age was 31 years (interquartile range [IQR] 26–36) and the median BMI was 27.3 kg/m² (IQR 24.6–31.0) (Table 1). Of the mothers with confirmed COVID-19, 30 (14.7%) were symptomatic. The most common obstetric complications were premature rupture of the membranes (23.4%), oligohydramnios or decreased amniotic fluid (14.7%) and preeclampsia spectrum disorder (12.3%). One hundred eight mothers (27.8%) had history of Cesarean section. In total, 373 mothers had serologic testing and 183 (49.1%) were seropositive. This proportion is significantly higher among infected than noninfected mothers (67.5% vs 27.7%, p < 0.00001). Among mothers with COVID-19, symptomatic and asymptomatic mothers had similar seropositivity rates (53.6% vs 69.8%, p = 0.090).

Table 1.

Characteristics of mothers with and without COVID-19 at Persahabatan Hospital, March–September 2020.

Characteristic	All mothers (N = 389)	Mothers without COVID-19 (N = 185)	Mothers with COVID-19 (N = 204)	p-value
Age, years^a	31 (26–36)	31 (26–36)	31 (26–36)	0.810
Body mass index, kg/m^2b,a	27.3 (24.6–31.0)	27.4 (25.0–31.2)	27.1 (24.0–30.5)	0.432
Pneumonia	32 (8.2)	4 (2.2)	28 (13.7)	<0.001
Premature rupture of membrane	91 (23.4)	42 (22.7)	49 (24.0)	0.759
Decreased amniotic fluid	57 (14.7)	28 (15.1)	29 (14.2)	0.798
Preeclampsia spectrum	48 (12.3)	28 (15.1)	20 (9.8)	0.110
Prior history of cesarean section	108 (27.8)	47 (25.4)	61 (29.9)	0.323
Seropositivity^b	183 (49.1)	48 (27.7)	135 (67.5)	<0.001
Caesarean section	371 (95.4)	174 (94.1)	197 (96.6)	0.238
Maternal mortality	6 (1.5)	3 (1.6)	3 (1.5)	1.000^c

P-values were obtained from Chi-squared test unless otherwise indicated. The bold values in table showed that the correlations are significants with p value <0.05.

^aQuantitative variables are presented as median (interquartile range) and difference between groups was assessed by Mann-Whitney U test.

^bCases with missing values for body-mass index (n = 3) and seropositivity (n = 16) were excluded pairwise.

^cFisher’s exact test.

Nearly all mothers (95.4%) underwent Cesarean section. In total, 393 neonates were delivered by 389 mothers (four mothers had twin pregnancy) with a median gestational age of 38 weeks (IQR 37–39). Significantly more neonates born to noninfected mothers had asphyxia at minute 1 of life (8.0% vs 2.0%, p = 0.005) and required resuscitation (8.5% vs 2.4%, p = 0.008) than those born to infected mothers. Neonates born to the former group also had higher frequencies of sepsis (26.6% vs 17.1%, p = 0.022) and TTN (10.1% vs 4.9%, p = 0.048) (Table 2).

Table 2.

Characteristics of neonates born to mothers with and without COVID-19 at Persahabatan Hospital, March–September 2020.

Characteristic	All mothers (N = 393)	Mothers without COVID-19 (N = 188)	Mothers with COVID-19 (N = 205)	p-value
Gestational age
<32 weeks	14 (3.6)	5 (2.7)	9 (4.4)	0.402
32–36 weeks	67 (17.0)	36 (19.1)	31 (15.1)
≥37 weeks	312 (79.4)	147 (78.2)	165 (80.5)
Male sex	200 (50.9)	98 (52.1)	102 (49.8)	0.639
Low birth weight	73 (18.6)	30 (16.0)	43 (21.0)	0.201
Asphyxia at minute 1	19 (4.8)	15 (8.0)	4 (2.0)	0.005
Asphyxia at minute 5	7 (1.8)	5 (2.7)	2 (1.0)	0.267^a
Neonatal diagnoses
Sepsis	85 (21.6)	50 (26.6)	35 (17.1)	0.022
Transient tachypnea of newborn	29 (7.4)	19 (10.1)	10 (4.9)	0.048
Pneumonia	19 (4.8)	9 (4.8)	10 (4.9)	0.967
Respiratory distress syndrome	21 (5.3)	10 (5.3)	11 (5.4)	0.984
Meconium aspiration syndrome	3 (0.8)	3 (1.6)	0 (0.0)	0.109^a
Pneumothorax	2 (0.5)	1 (0.5)	1 (0.5)	1.000^a
Need for resuscitation	21 (5.3)	16 (8.5)	5 (2.4)	0.008
Oxygen therapy during stay
Noninvasive ventilation	88 (22.4)	42 (22.3)	46 (22.4)	0.981
HFO or invasive ventilation	14 (3.6)	8 (4.3)	6 (2.9)	0.478
Infant laboratory studies
Hemoglobin, g/dL^b,c	15.7 (14.2–17.3)	15.6 (13.9–17.3)	15.8 (14.5–17.4)	0.404^c
Abnormal leukocyte count^b	32 (8.3)	11 (6.0)	21 (10.4)	0.113
Neutrophil/lymphocyte ratio^b,c	3.11 (2.30–4.14)	3.12 (2.30–4.17)	3.06 (2.29–4.06)	0.617^c
Platelet count, 10³/µL^b,c	303 (262–346)	302 (255–341)	305 (268–359)	0.086^c
Abnormal blood smear^b	31 (9.0)	16 (9.6)	15 (8.3)	0.671
C-reactive protein >5 mg/L^b	100 (26.5)	51 (28.0)	49 (25.0)	0.506
Seropositivity^b	126 (33.9)	28 (16.3)	98 (49.0)	<0.001
Neonatal COVID-19^b	9 (2.4)	4 (2.3)	5 (2.5)	1.000^a
Neonatal mortality	7 (1.8)	4 (2.1)	3 (1.5)	0.714^a

P-values were obtained from Chi-squared test unless otherwise indicated. HFO: high-flow oxygen. Abnormal leukocyte count was defined as leukocyte <5000 or >30,000 cells/µL. Abnormal blood smear was defined as grade 2 toxic granulation or grade 1 toxic granulation with hypersegmentation. The bold values in table showed that the correlations are significants with p value <0.05.

^aFisher’s exact test.

^bCases with missing values for hemoglobin (n = 8), leukocyte count (n = 8), neutrophil/lymphocyte ratio (n = 64), platelet count (n = 8), blood smear (n = 8), C-reactive protein (n = 15), seropositivity (n = 21), and neonatal COVID-19 status (n = 16) were excluded pairwise.

^cQuantitative variables are presented as median (interquartile range) and difference between groups was assessed by Mann–Whitney U test.

Of the 393 neonates, 372 underwent serologic testing, and 126 (33.9%) were seropositive. Neonates born to infected mothers were more likely to be seropositive than those born to noninfected mothers (49.0% vs 16.3%, p < 0.00001). Among the former group, neonates born to asymptomatic mothers were more likely to be seropositive than those born to mothers with symptomatic COVID-19 (52.4% vs 30.0%, p = 0.024) (Table 3).

Table 3.

Association between maternal symptomatic COVID-19 and maternal seropositivity, neonatal seropositivity, and neonatal COVID-19.

Characteristic	Mothers with COVID-19		p-value
Characteristic	Asymptomatic	Symptomatic	p-value
Maternal seropositivity	120/172 (69.8)	15/28 (53.6)	0.090
Neonatal seropositivity	89/170 (52.4)	9/30 (30.0)	0.024
Antibody transfer^a	89/119 (74.8)	9/15 (60.0)	0.229^b
Neonatal COVID-19	2/173 (1.2)	3/31 (9.7)	0.026 ^b

P-values are obtained from Chi-squared test. The bold values in table showed that the correlations are significants with p value <0.05.

^aNumber of seropositive mothers who had seropositive infant.

^bFisher’s exact test.

RT-PCR of nasopharyngeal swab specimen was performed for 377 neonates, of whom nine (2.4%) tested positive for SARS-CoV-2 (Table 4). Five of the neonates were born to mothers with COVID-19. Of the neonates born to mothers with COVID-19, those born to symptomatic mothers were more likely to be infected (9.7% vs 1.2%, p = 0.026). Serologic testing was performed for 8 of the infected infants, of whom one was seropositive. The median length of stay was 8 days for infected infants and 4 days for noninfected infants (p = 0.029). Three of the infected neonates had hyperbilirubinemia; one of them had asphyxia and was diagnosed with MAS and sepsis. The infant required mechanical ventilation for 6 days followed by noninvasive ventilation for 3 days. The remaining infected infants did not develop respiratory distress nor required any oxygen therapy during hospitalization. For 8 infants with repeat RT-PCR, all nasopharyngeal swab samples obtained 1 day following the positive test were negative for SARS-CoV-2.

Table 4.

Characteristics of confirmed neonatal COVID-19 cases at Persahabatan Hospital, March–September 2020.

Characteristic	Infant
Characteristic	1	2	3	4	5	6	7	8	9
Gestational age (weeks)	37	38	39	40	39	38	38	39	38
APGAR score (minute 1/5)	8/9	9/10	5/7	9/10	9/10	9/10	9/10	8/9	9/10
Age at positive RT-PCR (days)	13	2	<1	1	<1	2^a	2^a	1	1
Age at negative RT-PCR (days)	13	3	1	2	1	8	NA	2	2
Maternal COVID-19	Yes	Yes	No	No	No	Yes	Yes	No	Yes
Symptomatic COVID-19	Yes	No				Yes	No		Yes
Maternal pneumonia	Yes	No	No	No	No	No	No	No	Yes
Maternal SARS-CoV-2 serology	NA	+	−	−	−	−	+	+	NA
Neonate SARS-CoV-2 serology	NA	−	−	−	−	−	+	−	−
Neonatal respiratory distress	No	No	Yes	No	No	No	No	No	No
Neonatal hyperbilirubinemia	Yes		Yes			Yes
Meconium aspiration			Yes
Neonatal sepsis			Yes
Noninvasive ventilation (days)	-	-	3	-	-	-	-	-	-
Mechanical ventilation (days)	-	-	6	-	-	-	-	-	-
Length of stay (days)	21	13	17	3	14	6	2	6	8

NA: not available; RT-PCR: reverse transcriptase polymerase chain reaction.

^aInfants 6 and 7 initially tested negative at 1 day of life.

Seven infants (1.8%) died in this study, of whom 6 were preterm and all had low birth weight. Three of the deceased neonates had COVID-19-positive mothers. All seven neonates were diagnosed with RDS and sepsis. RT-PCR was performed for all seven neonates, and none were positive for SARS-CoV-2.

Discussion

Study population

During the study period, only mothers with confirmed or suspected COVID-19 were referred to Persahabatan Hospital. However, in many cases, asymptomatic mothers were referred based only on a positive rapid antibody test, especially earlier in the pandemic when RT-PCR testing was not widely available. Very few of these patients were found to have COVID-19, in agreement with the low positive predictive value of rapid antibody tests for detecting COVID-19 in the general population.¹⁶ As a result, we were able to observe neonatal outcomes of both infected and noninfected mothers. Missing data were handled using pairwise deletion to maximize the use of available data in each analysis. This approach was chosen because the proportion of missing values was low (<5%) and the data were assumed to be missing completely at random.

Seropositivity against SARS-CoV-2

We found a slightly higher seropositivity rate among mothers with asymptomatic COVID-19 than their symptomatic counterparts. This appears contrary to literature, which suggests that anti-SARS-CoV-2 IgG is less likely to develop and persists for a shorter period in asymptomatic COVID-19 patients than symptomatic ones.^17–20 It is possible that symptomatic mothers in this study were in earlier stages of infection compared to asymptomatically infected mothers and therefore less likely to have developed anti-SARS-CoV-2 IgG.²¹

Overall, 70.0% of seropositive mothers in our study transferred antibodies to their infants. This is a lower rate than observed by Flannery et al., who reported that of 78 mothers positive for anti-SARS-CoV-2 IgG, 72 (92.3%) had seropositive infants²² Whether this disparity reflects interpopulation biological differences is unclear. Maternal chronic infection and prematurity are known to affect transplacental IgG transfer, and maternal comorbidities such as malnutrition, diabetes and hypertension are postulated to play a role.²³

Incident neonatal COVID-19

Only 9 of the 377 tested neonates in this study had COVID-19, equivalent to a 2.4% neonatal infection rate. This is consistent with existing literature which suggests a low incidence of neonatal COVID-19,^12,15,24 although rates vary between studies. One study of 42 infants born to mothers with COVID-19 in Italy in March 2020 found 3 cases of neonatal SARS-CoV-2 infection. In two of these cases, the mother had breastfed without a mask before being diagnosed with COVID-19.¹³ One study of 342 infants born in India between June 2020 and January 2021 to mothers with COVID-19 found 50 (14.3%) infants infected with SARS-CoV-2.¹⁴ In the INTERCOVID multinational cohort study, neonatal SARS-CoV-2 infection was found in 54 out of 416 neonates (13.0%) born to mothers with COVID-19 between March and October 2020.⁸

Although the timing of maternal infection was generally in the late third trimester, limiting the window for transplacental antibody transfer, our findings suggest possible differences in neonatal seropositivity and outcomes based on maternal COVID-19 status.

Intrauterine transmission of COVID-19 has been described^25–27 but are decidedly rare. More likely, neonates acquire SARS-CoV-2 infection from their mothers during delivery or from other sources such as healthcare workers. In a review of 176 neonatal COVID-19 cases, 70.5% were linked to environmental exposure and another 17.3% to intrapartum transmission.⁹

Neonatal SARS-CoV-2 infection appeared to be more likely among infants born to symptomatically infected mothers than those born to asymptomatically infected mothers. The reason for this association is unclear. It is possible that these neonates are more susceptible to SARS-CoV-2 infection because they are less likely to have specific IgG compared to those born to mothers with asymptomatic infection. Indeed, only one of the infected infants were seropositive. Symptomatic patients are also more likely to transmit COVID-19,²⁸ and the risk of intrapartum transmission may be greater in cases with symptomatically infected mothers. Nonetheless, further studies are clearly warranted to confirm our findings.

Due to hospital policy and concerns of vertical transmission at the time, Cesarean section was widely favored while rooming-in and breastfeeding were invariably avoided. Therefore, association between these practices and neonatal COVID-19 was not examined. Nevertheless, these policies have since been reversed. There is currently a lack of evidence to support the role of Cesarean section in preventing possible vertical transmission²⁹ or the association between breastfeeding and incident neonatal COVID-19^8,9 if mask wearing is observed.¹³

Neonatal outcomes

There was a higher frequency of asphyxia and need for resuscitation among neonates born to COVID-19-negative mothers. This is likely incidental and related to the higher frequency of sepsis and TTN. While our data did not show maternal peripartum COVID-19 to adversely affect neonatal outcome, it is important to note that this retrospective study sampled liveborn infants admitted to the perinatology unit. The seemingly higher burden of neonatal complications in COVID-negative mothers likely reflects selection bias, referral patterns, and overlooked or misclassified infections. Many COVID-negative mothers were initially referred based on rapid antibody tests or clinical suspicion, not confirmed RT-PCR. Some may have had undiagnosed or early-stage infections, misclassifying them as negative. COVID-positive mothers were managed more aggressively and monitored closely, potentially improving neonatal outcomes via earlier interventions or elective Cesarean delivery. The hospital served as a COVID-19 referral center. Thus, noninfected mothers included in the cohort were a select group, often referred with complications, leading to overrepresentation of high-risk deliveries in the COVID-negative group. Uniform policies such as Cesarean section (95.4%) and formula feeding were applied, but the urgency or timing of delivery could differ between groups. Higher TTN and sepsis rates might stem from delayed elective procedures or compromised perinatal management in the non-COVID group due to triage limitations. False-negative RT-PCR tests are also possible, especially if testing was performed too early or under suboptimal conditions. Infections in COVID-negative mothers might have been missed, especially if only a single PCR test was done without follow-up. COVID-19 during pregnancy has been linked to a higher risk of preeclampsia spectrum disorder, medically indicated preterm birth, low birth weight, and severe neonatal morbidities.⁸

Of the nine COVID-19-positive infants, three had hyperbilirubinemia; one of them had respiratory distress and was diagnosed with MAS and sepsis. Hyperbilirubinemia and sepsis have been reported in neonates and young infants with COVID-19.^30–32 Reports of neonatal COVID-19 severity and outcome vary due to the limited case number and varying settings. One center in India reported respiratory distress and feeding intolerance in 4 out of 50 neonates (8%) with COVID-19,¹⁴ while another center reported 9 neonatal COVID-19 cases of whom 7 were symptomatic, including 4 cases with sepsis,³² In a United Kingdom prospective national surveillance that identified 66 neonates with COVID-19, one third required some form of respiratory support.²⁴

Comparison with large international studies

Our findings are largely consistent with data from large international studies, including the INTERCOVID and UKOSS cohorts. The INTERCOVID study, a multinational cohort involving over 2100 pregnant women across 18 countries, reported that maternal COVID-19 was associated with an increased risk of preeclampsia, medically indicated preterm birth, and neonatal complications including low birth weight and NICU admission.⁸ However, they also found that severe neonatal outcomes were uncommon when maternal infection occurred in late pregnancy, aligning with our observation that maternal COVID-19 was not associated with a higher incidence of acute neonatal complications. Similarly, the UKOSS study, which analyzed 66 neonates with confirmed SARS-CoV-2 infection in the United Kingdom, found that the majority had mild disease and that vertical transmission was rare.²⁴ These findings corroborate our data showing low neonatal infection rates (2.4%) and no increase in severe outcomes among neonates born to infected mothers. Importantly, both studies highlight that symptomatic maternal infection may carry higher risk of neonatal infection or complications, a trend also observed in our cohort.

Conclusion

This study found that maternal COVID-19 infection, particularly when occurring in late pregnancy, was not associated with an increase in acute neonatal complications. Higher rates of asphyxia, transient tachypnea of the newborn (TTN), sepsis, and the need for resuscitation were more frequently observed among neonates born to mothers without COVID-19 infection. Neonates born to symptomatic mothers had a higher risk of acquiring SARS-CoV-2 compared to those born to asymptomatically infected mothers. These findings suggest that the severity of maternal infection may affect the efficiency of antibody transfer and the risk of neonatal infection, highlighting the complex relationship between maternal infection status and neonatal health outcomes.

Strengths and limitations

To the best of our knowledge, this is the largest study to report maternal and neonatal COVID-19 status concurrently with paired maternal–neonatal serostatus against SARS-CoV-2. This study provides data for neonates of mothers with COVID-19 as well as noninfected mothers. This is also one of the only studies⁸ to report neonatal COVID-19 cases from Indonesia and the Southeast Asia region. There are, however, several limitations to our study.

Due to variations in gestational age and delivery mode, which may act as confounders, these factors should be considered in the interpretation of results. Further research with more detailed data on the timing of infection and adjusted analyses is needed to strengthen the understanding of maternal–neonatal COVID-19 transmission and its clinical implications.

The limited number of infected infants precludes meaningful identification of risk factors for neonatal COVID-19. While RT-PCR testing was routinely performed for neonates in this study, the timing of nasopharyngeal swab varies, making it difficult to discern the timing of infection. Moreover, RT-PCR on cord blood or placental tissue was not performed. Finally, this is a single-center study in a national referral hospital and findings, particularly neonatal COVID-19 incidence, is not generalizable to other maternity care settings. Nevertheless, this study provides a novel cohort of infants with infected and noninfected mothers, with novel cases of neonatal SARS-CoV-2 infection.

Footnotes

Acknowledgment

Our graditute to all staff of the obstetrics and gynecology department and Pediatrics department at Persahabatan Hospital for their invaluable contributions.

ORCID iDs

Agnes Yuni Purwita Sari

Jully Neily Kasie

Yuyun Lisnawati

Ethical considerations

Ethical approval for this study was obtained from the Health Research Ethics Committee, Persahabatan General Hospital with number 64/KEPK-RSUPP/6/2020.

Consent to participate

Written informed consent was obtained from all subjects before the study.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The costs of all diagnostic tests and treatments were covered by the Ministry of Health under national COVID-19 management program.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Trial registration

This research does not consist of any intervention.

Guarantor

Dr. Agnes Yunie Purwita Sari, SpA(K).

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