Birth weight serves as an important determinant of infant health in the future. Low birth weight is associated with a higher mortality rate, as well as can make an infant more susceptible to cardiovascular and metabolic disorders later in life.
Recently, a growing pool of evidence suggests that both maternal and fetal genetic factors can influence the birth weight of an infant.
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How can genetic factors influence birth weight?
According to scientific studies, shared genetic effects in the intrauterine environment can significantly influence the birth weight and future cardio-metabolic consequences of an infant.
Upon segregation of the direct effects of fetal genetic makeup and indirect effects of maternal genetic makeup on birth weight, it has been found that there are 190 independent association signals associated with low birth weight.
Maternal genetic analysis can be used to predict whether the birth will be preterm and whether key nutrients, such as glucose, are available at appropriate levels. Maternal glucose crosses the placenta and stimulates the secretion of fetal insulin, which subsequently triggers fetal growth.
It has been found that a high maternal glucose level is associated with higher infant birth weight. Moreover, genes that increase maternal insulin secretion and subsequently reduce maternal glucose levels are responsible for a reduction in insulin-induced fetal growth.
Using Mendelian randomization analysis, the study has shown that a higher infant birth weight is influenced by both direct fetal and indirect maternal effects of height-rising alleles.
Moreover, the findings indicate that the inverse correlation between birth weight and future development of type 2 diabetes is influenced by fetal genetic effects only. In contrast, the negative association between birth weight and adult systemic blood pressure is influenced by indirect effects of maternal blood pressure-rising alleles (which reduces infant birth weight) and the direct effects of the fetal genetic makeup associated with higher adult blood pressure.
Other maternal factors that influence infant birth weight include a number of pregnancies, gestational length, and mother’s birth weight. For example, babies born from first pregnancy are usually thinner and with reduced adiposity as compared to following pregnancies.
This may result from poor placental status due to hypertension and preeclampsia of the mother. Other reasons include a maternal smoking status and low birth weight of the mother.
The effect of maternal birth weight on infant birth weight may be associated with variations in the mitochondrial genome. A low infant birth weight is known to be related to a mitochondrial DNA variant at position 16189.
A common variant of H19 (H19+2992), which is a maternally expressed gene regulating the imprinting and expression of paternally expressed growth inducer namely insulin-like growth factor 2 (IGF2), is known to cause a higher level of IGF2 in the cord blood, increased maternal glucose level, and higher birth weight.
Also, it has been found in mice that knockout of placental-specific IGF2 promotor results in a temporary increase in placental nutrient transfer to favor fetal growth; however, this transient effect subsequently subsides, leading to low birth weight.