Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia

Abstract

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills.Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content.Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training.Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.

The effects of COVID-19 on placental morphology

“…These changes mainly include thrombosis, malperfusion and vasculopathy in both maternal and foetal circulations as summarized in Table 1 . Vascular changes may adversely affect the health of pregnant women and their unborn babies and cause severe health consequences [ 43 , 44 ].…”

“…Placental vascular changes due to COVID-19 infections during the third trimester have been extensively studied. Studies documented signs of maternal vascular malperfusion which included the presence of infarcts, thrombosis, increased syncytial knots, increased fibrin deposition, villous agglutination and accelerated villous maturation [ 44 , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [56] , [57] , [58] , [59] , [60] , [62] , [63] , [64] , [65] , 68 , 71 , 73 , 74 ]. Furthermore, subsequent studies that reported multi case investigations of placentae from COVID-19 positive mothers which presented different features of foetal vascular malperfusion including avascular villi, karyorrhexis, mural fibrin deposition, villous hypoplasia and chorangiosis [ 44 , 46 , 48 , 49 , 51 , 54 , 56 , 59 , 62 , 63 , 65 , 66 , 69 , 73 ].…”

“…Furthermore, this virus often results in severe hypoxemia in pregnancy therefore altering the oxygen distribution to the placenta, as it is dependent on the uterine blood flow, fetoplacental system and maternal oxygen saturation [ 79 ]. Hypoxia and ischemia can be identified in the placenta through the increase in syncytial knots, whilst foetal hypoxia can be identified in the circulation through the increase in erythroblasts and nuclear debris [ 52 , 58 , 63 , 64 , 67 , 73 ]. Hypoxia induced by COVID-19 can result in altering the development of blood vessels, the blood supply as well as the development of the placenta which can have a devastating impact on the growing foetus [ 80 ].…”

Potential molecular and cellular mechanisms for adverse placental outcomes in pregnancies complicated by SARS-CoV-2 infection—A scoping review

“…Respiratory chain subunit genes NADH:Ubiquinone oxidoreductase subunit A9 (NDUFA9), succinate dehydrogenase complex flavoprotein subunit A (SDHA) and cyctochrome C oxidase subunit 4I1 (COX4I1) were also decreased in symptomatic infected cases [ 30 ]. Mitochondrial DNA (mtDNA) was also decreased in infected placentae, potentially due to increased DNA oxidative damage [ 30 ], though another study found elevated mtDNA in infected placentae [ 29 ], indicating that further research is necessary to tease out the effect of SARS-CoV-2 infection on mtDNA levels. SARS-CoV-2 infection was also associated with aberrant mitochondrial reticulum and an increase in mitochondrial fission over fusion, accompanied by a decrease in genes involved in mitochondrial dynamics dynamin-1-like protein (DNM1L) and mitochondrial fission 1 protein (FIS1) [ 30 ] resulting in highly fragmented mitochondria [ 25 ].…”

Infeksi Covid-19 pada Ibu Hamil dan Kejadian Anomali Kongenital: Scoping Review

“…Namun, hubungan antara luaran perkembangan pada bayi dengan disfungsi mitokondria plasenta ibu yang terinfeksi covid-19 masih belum jelas. 13 Beberapa laporan kasus menemukan adanya MVM dan intervilositis histiositik kronis dengan nekrosis tropoblas pada plasenta ibu yang terinfeksi covid-19. 12,14,15,16 MVM plasenta ini dapat secara langsung mempengaruhi perkembangan janin dalam Rahim.…”