Unexplained preterm birth and related death:Does heavy metals play heavily

As per WHO 2019 data, globally, 15 million babies are born preterm every year and is the leading cause of death in children under the age of 5 years. India contributes one-fifth of global data with more than 3.5 million preterm birth per year (WHO, 2019). While less than 50% of the preterm birth is attributed to multiple maternal causes, more than 50% of cases are of unknown origin (Lawn et al., 2008; Blencowe et al., 2012). The risk of neonatal death due to complications of preterm birth is too high compared to term birth. Heavy metals such as mercury, cadmium, lead, arsenic, uranium, etc are well-known pollutants of the environment and could easily cross the placenta from maternal blood to reach the developing fetus (Gundacker and Hengstschläger, 2012). Heavy metals are well known to induce oxidative stress in the trophoblastic placental tissue (Singh et al., 2018). High levels of heavy metals were seen in maternal serum, resulting in multiple adverse birth outcomes (Kippler et al., 2012a, 2012b; Hu et al., 2016; Jiang et al., 2016; Yang et al., 2016; Sabra et al., 2017; Wai et al., 2017; Chen et al., 2018; Lin et al., 2018). High levels of heavy metals were also seen in maternal blood from the Indian population, resulting in adverse birth outcomes ( Awasthi et al., 2002). Heavy metals levels were seen in maternal and cord blood and placenta (Ong et al., 1993; Al saleh et al., 2011; Hu et al., 2015). We did not find any studies measuring the magnitude of multiple heavy metals in cord blood of babies born preterm.

The proposed study is a prospective cohort study containing two experimental groups. In the first group, 200 babies born preterm due to unexplained causes will be taken. In the second group, 400 babies born preterm due to known maternal causes will be taken. Both the groups include all the preterm babies (below 28 weeks, 28-32 weeks, and 33-37 weeks) born at various gestational ages. Cord blood (10 ml) will be collected in a vacutainer from the umbilical cord and placenta after birth, the blood will be collected from the placental side and not from the fetal side and will be collected only after clamping. Written informed consent will be obtained from all participating mothers. Blood collected will be allowed to clot and centrifuged at 3000rpm for 15 minutes for serum collection. Serum samples will be aliquoted until analysis for heavy metals. All the heavy metals will be measured at Thyrocare Technologies Ltd, which measures several heavy metals such as lead, mercury, arsenic, cadmium, uranium, etc through inductively coupled plasma mass spectrometry (ICP-MS) method. All the preterm babies from both groups will be assessed until one year of development using Bayley Scales of Infant Development III for cognitive, motor, social-emotional, and adaptive behavior