Beyond COVID‐19: Equitable epidemiology for studying the impact of maternal infections on neonatal mortality and morbidity

1South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 2Department of Science and Technology/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

There is a special hope and joy surrounding a birth and, therefore, it is especially poignant that neonatal mortality (deaths in the first 28 days of life) and long-term complications from diseases that occur during the neonatal period remain high throughout the world. 1 The first month of life is undoubtedly the most vulnerable period during childhood-almost one-third of all deaths happen on the day of birth and about three-quarters of neonatal deaths occur during the first week of life. 2 During the 21st century, we have witnessed incredible development in global health initiatives leading to substantial improvements in health outcomes, especially in child survival.
Although the number of overall child deaths is rapidly declining, from 1990 to 2020 the global annual reduction of deaths in children aged 1-59 months was 3.1%, while during the neonatal period, the reduction was 2.6%. As a result, the relative proportion of neonatal deaths among all under-5 deaths has actually increased from 40% in 1990 to 47% in 2020. 1 Globally in 2020, approximately 2.4 million newborns died at an estimated average rate of 17 deaths per 1000 live births; in comparison, the estimated probability of dying from 1 to 11 months of age was 11 deaths per 1000 live births, and from 1 year to 4 years of age was 9 deaths per 1000 live births. 1 To further decrease the burden of neonatal mortality, we will need to address the main causes of these deaths, which are different from the causes in older children.
Neonates primarily die because of preterm birth and intrapartumassociated complications and infections, including sepsis, meningitis, and pneumonia. 2 Of the more than half a million annual newborn deaths due to infections, the large majority occur in low-and middle- bias-corrected gestational age estimate, they found that women living with HIV compared with those without HIV had similar risks of overall pregnancy loss and of preterm delivery; the risk of delivering small for gestational age births was, however, higher among women living with HIV. Furthermore, among women living with HIV, outcomes were similar by ART initiation timing. The results from this study are reassuring that the increasingly safe and efficacious ART regimens not only lead to improved immunologic status, but also have a less negative impact on pregnancy outcomes compared with earlier treatments. 7 Nonetheless, the number of infants born HIV-exposed uninfected is growing worldwide, and these infants have been shown to be at increased risk of mortality, hospitalisation, severe respiratory infections, and potentially longer-term health outcomes. The rising incidence of childhood obesity is a challenge globally. Maternal obesity is known to influence infant weight gain; however, this association is less clear in children born to women living with HIV, where factors such as in utero exposure to the HIV viral particles and ART may play a role in weight gain. 8 In this special issue, Bengtson and colleagues 5 reported that 20% of infants were overweight or obese by 12 months of age in their study in South Africa, and identified maternal body mass index as being positively associated with higher infant weight regardless of maternal HIV status. Therefore, it will be important to include nutritional advice and weight management in routine antenatal and infant care services.

Among neonates and young infants, group B Streptococcus (GBS)
is a leading cause of invasive bacterial disease, with a global incidence of 0.49 cases per 1000 live births and an associated case fatality rate of 8.4%; GBS infection may also result in stillbirth and major longer-term neurodevelopmental sequelae. 9 Although maternal GBS carriage rates vary substantially by world region, approximately 18% of pregnant women are colonised with GBS in their genitourinary tract that can be vertically transmitted to the newborn. In highincome countries, pregnant subjects are screened for GBS carriage in the weeks prior to delivery to identify those who could benefit from intrapartum antibiotic prophylaxis. In the absence of such preventive strategies, approximately 1-2% of newborns from mothers colonised with GBS will develop invasive disease. 9 Despite global advocacy to highlight the GBS burden, research gaps remain and implementation of preventive strategies in LMICs is urgently needed.
In another article in this special issue, by evaluating whether diagnosis of maternal GBS colonisation could be done by real-time polymerase chain reaction (PCR) at the time of delivery, Kugelman and colleagues 6 concluded that PCR had good sensitivity and specificity compared to culture to detect GBS. They suggested that the need for maternal prophylactic antibiotics could be substantially reduced by using this strategy compared with antepartum universal culture screening or intrapartum risk-factor assessment. While PCR testing is still expensive and unavailable in many LMIC settings, the costeffectiveness of this approach and its future potential use as pointof-care should be considered.
To improve maternal health and neonatal survival, it is crucial to ensure that every pregnant woman has access to antenatal care and lifesaving interventions during the intrapartum, delivery, and postnatal periods. These can only be introduced if high-quality evidence is available to support their implementation and will thus require ob-  11 The applicability and success of these are dependent, however, on the quality of record keeping, which needs to be strengthened in LMICs.
Given the well-known impact of infections in pregnancy, much focus and urgency has been given to studying and mitigating the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy in the last 2 years. Hopefully, this renewed focus on the impact of infectious diseases on pregnancy, birth outcomes, and neonatal growth and development will also extend to other infections that are the cause of many potentially preventable diseases, not just in the neonatal period, but beyond.

A B O UT TH E AUTH O R S
Stephanie Jones is a medical doctor and is currently a PhD fellow