Abstract
This cohort study estimates associations between mode of delivery (vaginal vs cesarean delivery) and maternal and neonatal birth outcomes among SARS-CoV-2–infected women giving birth in Spain.
Data from China found severe complications in 8% of pregnant women with coronavirus disease 2019 (COVID-19).1 However, the high rate of cesarean deliveries (>90%) in Chinese reports is concerning,2 and whether mode of delivery is associated with maternal complications or neonatal transmission is unknown.3 We assessed births to women with COVID-19 by mode of delivery.
Methods
Women with singleton pregnancies and a positive reverse transcriptase–polymerase chain reaction (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 12 and April 6, 2020, and who delivered within the next 14 days at 96 level 2 or level 3 maternity hospitals throughout Spain were included.
The study was approved by the national ethics committee. Oral informed consent was obtained.
Pregnant women were tested if they presented with symptoms compatible with COVID-19 or a history of potential exposure; additionally, universal screening was started in some hospitals in April. Newborns had a nasopharyngeal swab obtained for RT-PCR within 6 hours of life.
Mothers were stratified by symptom severity at admission as asymptomatic, mild, or severe (need for advanced oxygen support: high-flow nasal cannula, noninvasive ventilation, or mechanical ventilation).
Maternal outcomes were defined as severe if mothers required advanced oxygen support or admission to the intensive care unit (ICU) or had signs of sepsis with hypoperfusion/organ dysfunction. Clinical deterioration was defined by an increased need for oxygen supplementation after delivery.
Neonatal outcomes considered were neonatal ICU (NICU) admission and rates of SARS-CoV-2 perinatal transmission.
Multivariable logistic regression was performed assessing the association between mode of delivery and maternal and neonatal outcomes among patients with mild symptoms, adjusting for maternal age, body mass index, comorbidities, need for oxygen supplementation at admission, abnormal chest x-ray findings at admission, nulliparity, smoking, and prematurity. Stata version 14 (StataCorp) was used. A 2-tailed P < .05 defined statistical significance.
Results
Of 82 pregnant patients included, 4 presented with severe COVID-19 symptoms, including 1 with concomitant preeclampsia; all 4 underwent cesarean delivery and required ICU admission.
Seventy-eight patients presented with no or mild COVID-19 symptoms, including 11 patients requiring oxygen supplementation. Forty-one (53%) delivered vaginally and 37 (47%) by cesarean delivery, 29 for obstetrical indications and 8 for COVID-19 symptoms without other obstetrical indications. Women with cesarean deliveries were more likely to be multiparous, be obese, require oxygen at admission, and have abnormal chest x-ray findings than those delivering vaginally (Table 1). No patients with a vaginal delivery developed severe adverse outcomes, while 5 (13.5%) with cesarean delivery required ICU admission. Two patients (4.9%) with a vaginal delivery had clinical deterioration after birth vs 8 (21.6%) with cesarean delivery. After adjustment for potential confounding factors, cesarean birth was significantly associated with clinical deterioration (adjusted odds ratio, 13.4; 95% CI, 1.5-121.9; P = .02) (Table 2).
Table 1. Maternal Characteristics, Clinical Presentation, and Obstetrical Management.
| Characteristics | Asymptomatic/mild COVID-19 symptoms | Severe COVID-19 symptoms and cesarean delivery (n = 4) | |
|---|---|---|---|
| Vaginal delivery (n = 41) | Cesarean delivery (n = 37) | ||
| Maternal characteristics | |||
| Age | |||
| Median (range), y | 35 (19-43) | 33 (19-48) | 36 (22-47) |
| >35, No. (%) | 21 (51.2) | 18 (48.7) | 2 (50.0) |
| Parity, No. (%) | |||
| Nulliparous | 16 (39.0) | 9 (24.3) | 1 (25.0) |
| Multiparous >3 | 3 (7.3) | 5 (13.5) | 0 |
| Comorbidities, No. (%) | |||
| Anya | 14 (34.1) | 11 (30.6) | 1 (25.0) |
| Gestational diabetes | 1 (2.4) | 0 | 0 |
| Preeclampsia | 1 (2.4) | 2 (5.6) | 1 (25.0) |
| Asthma | 3 (7.3) | 3 (8.3) | 0 |
| Smoking, No. (%) | 3 (7.3) | 3 (8.3) | 0 |
| BMI | |||
| Median (range) | 23 (17-35) | 26 (19-38) | 23 (22-30) |
| >30, No. (%) | 3 (8.8) | 15 (36.6) | 1 (25.0) |
| COVID-19 history and prepartum clinical presentation | |||
| Signs and symptoms at presentation, No. (%) | |||
| Asymptomatic | 13 (31.7) | 9 (25.0) | NA |
| Oxygen supplementation at admission | 4 (9.8) | 7 (18.9) | 4 (100.0)b |
| Diagnostic tests, No. (%) | |||
| Abnormal chest x-ray | 8 (19.5) | 12 (32.4) | 3 (75.0) |
| Abnormal ALT/AST | 5 (12.2) | 0 | 0 |
| Lymphopenia (<1.0 × 109/L), No. (%) | 4 (9.8) | 2 (5.6) | 1 (25.0) |
| Delivery management | |||
| Time from onset of symptoms to delivery, median (range), d | 2 (0-14) | 1 (0-10) | 4 (1-6) |
| Gestational age at delivery | |||
| Median (range) | 39 wk 1 d (27 wk 3 d–41 wk 3 d) | 38 wk 3 d (25 wk 0 d–41 wk 4 d) | 29 wk 6 d (28 wk 0 d–34 wk 0 d) |
| Preterm birth, No. (%) | |||
| 34 wk to <37 wk | 4 (9.8) | 10 (27.0) | 1 (25.0) |
| Iatrogenic preterm birth | 1 (25)c | 4 (40.0)c | 1 (100.0)d |
| <34 wk | 3 (7.3) | 4 (10.8) | 3 (75.0) |
| Iatrogenic preterm birth | 0 | 3 (75.0)e | 3 (100.0)d |
| Premature rupture of membranes, No. (%) | 9 (22.0) | 9 (24.3) | 0 |
| Preterm premature rupture of membranes, No. (%) | 3 (7.3) | 4 (10.8) | 0 |
| Obstetrical management, No. (%) | |||
| Prelabor cesarean delivery | NA | 13 (35.1) | 4 (100.0) |
| Induction of labor | 8 (19.5) | 8 (21.6) | 0 |
| Spontaneous onset of labor | 33 (80.5) | 16 (43.2) | 0 |
| In-labor cesarean delivery | NA | 24 (64.9) | 0 |
| Instrumental delivery | 12 (29.3) | NA | NA |
| Anesthesia, No. (%) | |||
| Locoregional analgesia | 32 (78.0) | 32 (86.5) | 2 (50.0) |
| General anesthesia | NA | 5 (13.5) | 2 (50.0) |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); COVID-19, coronavirus disease 2019; NA, not applicable.
In the vaginal delivery group, other maternal complications included hypothyroidism (n=3), epilepsy (n=1), Subek muscular dystrophy (n=1), myopathy (n=1), heterozygous factor V mutation (n=1), psychiatric disorders (n=3), unspecified autoimmune disease (n=1), hyperprolactinemia (n=1), gastritis (n=1), vitiligo (n=1), and chronic hepatitis C infection (n=1). In the cesarean delivery group, other maternal complications included hypothyroidism (n=2), homocysteine mutation (n=1), anti-Kell alloimmunization (n=1), concomitant pyelonephritis (n=1), myomatosis (n=1), mutation of methylenetetrahydrofolate reductase (MTHFR) (n=1), ischemic cardiomyopathy (n=1), and depressive disorders (n=1).
These patients required advanced oxygen support (eg, high-flow nasal cannula or continuous positive airway pressure).
Indications for iatrogenic preterm birth at ≥34 weeks’ gestation included maternal COVID-19 symptoms without other obstetrical reasons in 4 (1 vaginal delivery after induction of labor and 3 prelabor cesarean deliveries) and preeclampsia in 1 (cesarean delivery after failure of induction).
All iatrogenic preterm births were performed in relation to COVID-19 in the mother without other obstetrical indications.
Indication for iatrogenic preterm birth at <34 weeks’ gestation included 2 patients with COVID-19 symptoms without any other obstetrical indications for delivery (prelabor cesarean deliveries) and 1 patient with abnormal findings on fetal cardiac monitoring and suspected fetal asphyxia leading to prelabor cesarean delivery.
Table 2. Maternal and Neonatal Outcomesa.
| Outcomes | Asymptomatic/mild COVID-19 symptoms | Severe COVID-19 symptoms and cesarean delivery, No. (%) (n = 4) | |||
|---|---|---|---|---|---|
| Vaginal delivery, No. (%) (n = 41) | Cesarean delivery, No. (%) (n = 37) | Odds ratio (95% CI) | Adjusted odds ratio (95% CI) | ||
| Maternal outcomes | |||||
| Severe adverse outcomes | 0 | 5 (13.5) | NA | NA | 4 (100.0) |
| Severe pneumonia | 0 | 3 (8.1) | 2 (50.0) | ||
| Sepsis | 0 | 0 | 1 (25.0) | ||
| Postnatal intensive care unit admission | 0 | 5 (13.5) | 4 (100.0) | ||
| Length of stay, median (range), d | NA | 10 (2-18) | 4 (1-13) | ||
| Mechanical ventilation | 0 | 4 (10.8) | 2 (50.0) | ||
| Clinical deterioration | 2 (4.9) | 8 (21.6) | 5.4 (1.0-54.6) | 13.4 (1.5-121.9) | 2 (50.0) |
| Neonatal outcomes | |||||
| Neonatal intensive care unit admission | 8 (19.5) | 11 (29.7) | 1.7 (0.5-5.8) | 1.2 (0.3-4.5) | 3 (75.0) |
| SARS-CoV-2 perinatal transmission rates | |||||
| Total with tests at birth | 41 (100) | 30 (81.1) | 1 (25.0) | ||
| Suspectedb | 2 (4.9) | 1 (3.3) | 0.7 (0.0-13.6) | NA | 0 |
| Confirmedc | 0 | 2 (5.4) | NA | NA | 0 |
| Secondary outcomes | |||||
| Apgar score <5 at 5 min | 0 | 3 (8.1) | 0 | ||
| Arterial umbilical pH <7.10 | 3 (7.3) | 3 (8.1) | 0 | ||
| Birth weight, median (range), g | 3060 (940-4750) | 3210 (910-4510) | 1450 (1110-1580) | ||
| <10th percentile | 1 (2.4) | 0 | 0 | ||
| Breastfeeding | 23 (56.1) | 19 (51.4) | 0 | ||
Abbreviations: COVID-19, coronavirus disease 2019; NA, not applicable; RT-PCR, reverse transcriptase–polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Odds ratios and 95% CIs are based on multivariate logistic regression analysis assessing risk of severe maternal outcomes, clinical deterioration, neonatal intensive care unit admission, and perinatal transmission associated with mode of delivery among patients with mild symptoms. Estimates were adjusted for confounding factors and heterogeneity between the 2 groups (maternal age >35 years, body mass index >30, maternal comorbidities, need for oxygen supplementation at admission, abnormal chest x-ray findings at admission, nulliparity, smoking, and prematurity).
Positive RT-PCR result at birth. Two were preterm births in which testing was performed after initial resuscitation; the other newborn had contact with his mother immediately after birth.
Repeat positive RT-PCR result and compatible symptoms.
Eight newborns (19.5%) delivered vaginally and 11 (29.7%) born by cesarean delivery were admitted to the NICU. After adjustment for confounding factors, cesarean birth was not significantly associated with an increased risk of NICU admission (adjusted odds ratio, 1.2; 95% CI, 0.3-4.5; P = .76).
Three (4.2%) of 72 newborns tested within 6 hours after birth had a positive SARS-CoV-2 RT-PCR result. Repeat testing at 48 hours was negative. None developed COVID-19 symptoms within 10 days.
Two other newborns, both cesarean deliveries at term, developed COVID-19 symptoms within 10 days. Though initial testing at birth was negative, repeat testing was positive. Both newborns were in contact with their parents immediately after birth. Symptoms resolved within 48 hours.
Discussion
In this cohort of pregnant women in Spain, severe adverse maternal outcomes occurred in 11% (9/82), 4 of whom presented with severe and 5 with mild COVID-19 symptoms.
Among patients with mild symptoms at presentation, all patients with a vaginal birth had excellent outcomes. In contrast, 13.5% of women undergoing cesarean delivery had severe maternal outcomes and 21.6% had clinical deterioration. Women undergoing cesarean delivery may have been at higher risk of adverse outcomes, but after adjusting for confounding factors, cesarean birth remained independently associated with an increased risk of clinical deterioration. The physiological stress induced by surgery is known to increase postpartum maternal complications.4,5
Limitations include a lack of sufficient information on newborns to determine vertical transmission. The lack of association between cesarean delivery and risk of NICU admission may have been related to the lack of statistical power. Also, the 95% CIs around the odds ratios for cesarean birth and clinical deterioration were wide and the estimates fragile.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
References
- 1.Chen L, Li Q, Zheng D, et al. Clinical characteristics of pregnant women with Covid-19 in Wuhan, China. N Engl J Med. Published online April 17, 2020. doi: 10.1056/NEJMc2009226 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Della Gatta AN, Rizzo R, Pilu G, Simonazzi G. Coronavirus disease 2019 during pregnancy: a systematic review of reported cases. Am J Obstet Gynecol. Published online April 18, 2020. doi: 10.1016/j.ajog.2020.04.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kimberlin DW, Stagno S. Can SARS-CoV-2 infection be acquired in utero? more definitive evidence is needed. JAMA. Published online March 26, 2020. doi: 10.1001/jama.2020.4868 [DOI] [PubMed] [Google Scholar]
- 4.Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ Task Force statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2):1901208. doi: 10.1183/13993003.01208-2019 [DOI] [PubMed] [Google Scholar]
- 5.Sandall J, Tribe RM, Avery L, et al. Short-term and long-term effects of caesarean section on the health of women and children. Lancet. 2018;392(10155):1349-1357. doi: 10.1016/S0140-6736(18)31930-5 [DOI] [PubMed] [Google Scholar]