Nitric oxide synthase dysfunctionality in the umbilical cord vascular system during twin birth correlates with maturity and birth weight of the neonates

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The maternal physiological state during pregnancy have an excess demand for oxygen supply which can easily disrupt the redox homeostasis balance. There is a change in the maternal haemodynamic profile with an increased cardiac output, reduced systemic vascular resistance and blood pressure (de Haas et al., 2017). In response to this high oxygen demand red blood cell (RBC) mass level steadily increases by 20-30% from 8 to 10 weeks of the gestational period till the end of pregnancy (Foley, 2018). In connection to that, there are increasing evidences of enhanced oxidative insults during intrauterine development leading to severe abnormalities or pathological states like spontaneous miscarriage, preterm delivery, preeclampsia, ectopic pregnancy, intrauterine growth restriction (IUGR), placental abruption, perinatal death etc. Moreover, in cases of multiple/twin pregnancy there is an additional stress with the greater risks of miscarriage, anaemia, preterm delivery, gestational hypertensive disorders, IUGR, diabetes operative delivery and related postnatal and neonatal illnesses. Modern usage of in-vitro fertilization (IVF) therapies led to higher incidence of multiple pregnancies. There have been relevant data on the increasing foetal, neonatal and perinatal mortality rate of 3-6 times in twin and 5-15 times in other multiple pregnancies with comparison to the singleton pregnancies. During pregnancy, the connection between the mother and the foetus is provided by the placenta and the umbilical cord. The umbilical cord vascular system is the sole pathway of oxygen and nutrient transport to the foetus from the placenta. Therefore, the major obstetric complications are directly or indirectly connected to the placental or umbilical cord disorders causing intrauterine hypoxia and/or impaired blood flow to the developing foetus. The major part of umbilical cord lacks innervations and hence the vascular tone is mainly regulated by nitric oxide (NO), i.e. derived from the endothelial nitric oxide synthase (NOS3). The NO being a potent vasoactive agent causes vasodilation and increases the rate of perfusion, nutrient and oxygen supply. Usually intensive prenatal care and surveillances are done in high risk cases like multiple/twin pregnancy by the advanced non-invasive biomedical devices. The usage of high performance equipment like Blood oxygen level-dependent–magnetic resonance imaging was utilized to study changes in the placental oxygenation status in human pregnancies. It can also assess the placental perfusion and oxygen transport. Similarly, ultrasound and Doppler flow measuring techniques not only can visualize the umbilical cord but simultaneously can assess the foetal blood flow parameters through the umbilical cord vessels. These approaches can easily detect any abnormalities in the umbilical cord circulation, but lacks to highlight the underlying molecular mechanisms behind any kind of impaired functionality in the foetal vascular system that can highly influence the in-utero development. Further on this topic we elaborated in details.

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