Why the Silent Pandemic of Stillbirths Following COVID-19?

The world is in the midst of a major health crisis as coronavirus disease 2019 (COVID-19) continues to spread at an alarming rate and claim an ever-increasing number of lives. Some countries are experiencing their fifth or sixth waves of COVID-19 transmission, with no end to this situation in the foreseeable future.¹ The COVID-19 pandemic has affected every segment of the population. The effects of COVID-19 on pregnant women and adolescents as well as geriatric, child, and even mental health have been reported.^2,3 However, there have been few studies of the impact on the health and wellbeing of the unborn fetus. While direct effects on abortion, preterm delivery, premature rupture of membranes, preeclampsia, and fetal growth restriction have been described,⁴ indirect effects on fetal health are less evident but far more disturbing and damaging.

COVID-19 has had a significant impact on maternal, fetal, and newborn health globally. Much attention has been focused on maternal and infant mortality, stillbirths are often not considered in policy framing and analysis. According to joint estimates released by United Nations International Children’s Emergency Fund, the World Health Organization, the World Bank Group, and the Population Division of the United Nations Department of Economic and Social Affairs, a stillbirth occurs every 16 seconds.⁵ The report also warns that with the disruption of antenatal care services during the COVID-19 pandemic, some regions may see a 10%–20% increase in stillbirths over the next 12 months. Indeed, an increase in stillbirths has already been reported in a few low- and middle-income countries.⁶ This may be partly attributable to stay-at-home orders and reluctance to visit the hospital for fear of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19; however, there may be multiple causes. For example, with fewer antenatal visits and fetal ultrasound scans, an aneuploid, structurally malformed, or growth-restricted fetus may not be detected, adversely affecting the early diagnosis and timely management of such high-risk pregnancies. Additionally, women—especially those in their first pregnancy—may be unaware of warning signs that should prompt them to visit their healthcare provider. Reduced fetal movements,⁷ pedal edema, and other conditions may not be noticed by the women but are potential signs of grave diseases. Finally, an important factor that may contribute to the rise in stillbirths is a decline in institutional deliveries, nonavailability of trained birth attendants, and inability of patients to access healthcare facilities because of lockdowns and lack of transportation during the pandemic. All stillborn fetuses should be subjected to a complete physical examination, autopsy, and karyotype analysis to establish the etiology to prevent potential recurrence in a subsequent pregnancy.

There have been no reports to date of COVID-19 causing congenital malformations in the fetus, but cases of increased nuchal translucency, first-trimester hydrops, and calcification of the fetal gall bladder and bowel have been reported.^8,9 Transmission of SARS-CoV-2 from the placenta to amniotic fluid and fetal membranes has also been documented, and there have been cases in Ireland of severe placentitis leading to placental damage in patients infected with SARS-CoV-2.¹⁰ A gross examination revealed white streaks and nodules occupying large portions of the placental disc that could not be attributed to other causes.¹⁰ Fetal and maternal vascular malperfusion, fibrinoid necrosis, and chronic villitis are pathologic placental findings; consequent increases in preeclampsia, fetal growth restriction, preterm delivery, and adverse neonatal outcomes are inevitable. Elevated cytokine and interferon levels have been observed in mothers with COVID-19 during pregnancy. Interferons can affect the developing lungs and brain, leading to long-term respiratory or neurologic manifestations.¹¹ High levels of tumor necrosis factor-alpha are also known to disrupt neural tube development, predisposing the fetus to neural tube defects.¹² Additionally, lung damage caused by virus infection during pregnancy places a strain on the already overburdened cardiovascular system of the mother, predisposing the fetus to hypoxemia and fetal distress.

Antenatal care has undergone many changes during the COVID-19 pandemic, with restrictions on the number of patient visits and teleconsultation and home-based care being encouraged as an alternative.^5,13 While these approaches are appealing in theory, their implementation is challenging in developing countries. With a global usage rate of just over 50%, less than one-third of the population in Africa, Middle East, and South Asia have access to the internet.¹⁴ A suboptimal or nonexistent telecommunication infrastructure and internet connectivity coupled with low literacy rates are barriers to implementing teleconsultation services in remote areas. Close monitoring of the fetus through ultrasound scans performed daily or on alternate days can improve fetal prognosis in situations such as fetal growth restriction with Doppler abnormalities, twin-twin transfusion syndrome, and Rh isoimmunised pregnancy. Telemedicine and home-based care are in no way sufficient to monitor these pregnancies, which will worsen the prognosis. Healthcare facilities in urban areas are overwhelmed with patients affected by COVID-19, and healthcare workers including maternity specialists have been reassigned to their care. This has created challenges for the provision of antepartum fetal screening and surveillance services, with the burden being borne by the mother and fetus.

Chromosomal abnormalities and structural malformations have far-reaching consequences on fetal and neonatal health. Most tests used to assess fetal wellbeing are time-sensitive and cannot be delayed.¹⁵ Improvements in ultrasound technologies and increased availability of early screening tests allow time for safe pregnancy termination of an affected fetus in the first or early second trimester. However, because of the fear of SARS-CoV-2 infection, many pregnant women are delaying their check-ups until the late second trimester or even third trimester, thus missing out on the combined preeclampsia screening and first-trimester scan for anomalies such as nuchal translucency. Invasive diagnostic procedures such as amniocentesis and chorionic villus sampling have likewise declined.⁷ Some centers have adopted cell-free fetal DNA testing to screen for aneuploidy during the pandemic. The test is more sensitive and specific than the aforementioned diagnostic methods⁷ and reduces the number of patient visits, thereby diminishing the need for invasive procedures. In developing countries like India, the cost and availability of the test have always been an issue; women elect to forego antenatal screening altogether rather than take these expensive tests. This could lead to an increase in live births with Down syndrome and other aneuploidies.

Fetal and perinatal medicine, a specialized branch of obstetrics focusing on the fetus’ health and wellbeing, has become an essential part of medical practice. The fetus as a patient is a concept that has received significant attention in recent years as advances in pre- and perinatal medicine have made the fetus visible, examinable, approachable, and treatable. However, this belief only holds if the mother undergoes routine examinations throughout her pregnancy. The COVID-19 pandemic has been a major setback to the very concept of a fetal patient. On the one hand, most pregnant women have not made regular visits to their healthcare provider for fear of SARS-CoV-2 infection, leading to delays in interventions such as intrauterine blood transfusions and radiofrequency ablation of anastomotic vessels in twin-twin transfusion syndrome and twin reversed arterial perfusion that are lifesaving for the fetus. On theother hand, getting infected with SARS-CoV-2 during a routine check-up can cause even greater harm to the fetus.

Fetal medicine services are an integral part of antenatal care. Maternity workers should not be reassigned to other services because even a slight compromise in maternal and child health facilities can have far-reaching consequences for society.¹⁶

Although vertical transmission of SARS-CoV-2 is theoretically possible, transmission rates are not higher than that of other congenital infections.¹⁷ Healthcare professionals should also be aware that most fetal interventions performed using proper personal protective equipment and infection control measures pose little additional risk to the mother, fetus, or themselves. When adequate infection control measures are enforced and clinical triage is performed, the rate of horizontal transmission to frontline healthcare workers is <6%.¹⁸ Greater awareness of the importance and time-sensitive nature of prenatal monitoring and testing can increase their acceptance by pregnant women.¹⁹