Every year, nearly 303,000 infants die within 24 hours of being born. A staggering 99% of these neonatal deaths occur in low and middle-income countries, where access to quality maternal and neonatal care is often limited. The Born Strong Initiative strives to bridge this gap by bolstering maternal immune resilience, aiming to reduce these heartbreaking statistics and give every child a fighting chance from their very first breath.

Malnutrition contributes to nearly 45% of all deaths among children under the age of five. Maternal nutrition during pregnancy plays a pivotal role in fetal development, affecting a child's health for life. The Born Strong Initiative recognizes the profound impact of maternal health on infants and is dedicated to strengthening immune systems to provide a brighter, healthier future for the youngest members of our global family.

This issue extends beyond low and middle-income countries, affecting 1 in 12 babies in the US. Shockingly, these rates double among Aboriginal populations and African American mothers. What's concerning is that these statistics have remained stagnant for decades, reflecting our limited understanding of the causes of preterm birth. Equally troubling is the absence of vaccines, diagnostics, or therapeutics to effectively prevent and manage this pressing health challenge.

Lead Pl: Dr. Christine Stabell Benn, University of Southern Denmark

Observations suggest that maternal BCG vaccination may reduce the incidence of adverse pregnancy outcomes (BMC Public Health. 2021 PMID: 34140010). Live vaccines such as BCG and measles vaccine (MV) have broad beneficial effects far beyond their target pathogens (Lancet Infect Dis. 2020 PMID: 32645296).
To assess the possibility of immune modulation in the mother prior to pregnancy via BCG or MV, we are conducting a RCT in Guinea Bissau where 3.200 healthy fertile women are randomized to receive BCG, MV vs neither prior to conception, are followed throughout their pregnancy with standardized blood sample and clinical metadata collection for the mother and her baby. The first 450 women (150 in each arm) have already been enrolled, and the first pregnancies recorded.

Lead Pl: Dr, Michelle Giles, Monash University and Peter Doherty Institute for Infection and Immunity

Observations suggest that immunization during pregnancy with the recommended vaccines, influenza and pertussis, could drastically reduce incidence of adverse pregnancy outcomes (stillbirth, preterm birth), independent of the effect on influenza or pertussis disease (Front lmmunol. 2021 PMID: 34557193).
The mechanisms responsible for this pathogen-agnostic benefit are now being investigated in the PREMITUR study. 400 women and their babies will be followed longitudinally throughout pregnancy and beyond, with biological samples
collected from both mother and baby to be analyzed in a multiomics approach via machine learning to reveal signatures of vaccination•associated protective signals.

Lead Pl: Prof Kevin Kain, University of Toronto, Canada

The AGREE study is a randomised controlled trial with the primary objective to determine if daily antenatal oral supplementation with 4g L-citrulline can reduce adverse pregnancy outcomes (defined as a composite of fetal loss, infants born small for gestational age (SGA) or with low birth weight (LBW), or preterm birth) among pregnant women at high risk of malaria and protein undernutrition in Kenya. Outcomes about neonatal infection, mortality and development will also be collected.

Lead Pl: Dr. Petra Arck, University Medical Center Hamburg

The PRINCE study (PRenatal ldeNtification of Children's HEalth) is a prospective longitudinal pregnancy cohort study which commenced in 2011 at the University Medical Center Hamburg. It is one of the most comprehensive cohorts of pregnant woman in Europe. Pregnancy complications were recorded and included approx. 7-8 % of preterm birth, among other complications such as
gestational diabetes or stillbirth. The health and early hfe environment of the children born in the PRINCE study is documented using questionnaires. sent between the age of six month to four years. Queries include the application of vaccines (time point, specific vaccine used) and the incidence of infections. At the age of five years, the children participate in an on-site visit, where a physical examination is performed and blood is taken. Also, possible adverse effects to vaccines have been documented. To date. approx. 350 children have been seen at the age of five years. Analysis of samples is in progress.  

Pl  Nima Aghaeepour

Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies.
Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring, risk for stillbirth, preterm birth. and the development of treatments to prevent or minimize complications. Our experts in this space have successfully developed the platform.
Translating these into non-invasive (e.g. urine samples assessed like the covid RAT test) point of care (PoC) tests is our next step to make easier longitudinal monitoring. even at home or in remote settings.

Pl; Nima Aghaeepour; Negar Tavasso1ian

Wearables allow continuous, non-invasive monitoring of gestational health (mother and fetus) at home and in remote settings. The benefits of this approach are numerous. The technology has long been available. Missing was the ability to reliably extract meaning from the noise. Our team has now accomplished this. We now will test their breakthrough discoveries in the field.