1.Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring.
Jia Bi QIN ; Liu LUO ; Meng Ting SUN ; Peng HUANG ; Ting Ting WANG ; Sen Mao ZHANG ; Jin Qi LI ; Yi Huan LI ; Le Tao CHEN ; Jing Yi DIAO ; Ping ZHU
Biomedical and Environmental Sciences 2022;35(1):45-57
OBJECTIVE:
This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.
METHODS:
A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.
RESULTS:
After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.
CONCLUSIONS
In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
Adult
;
Cytochrome P-450 Enzyme System/genetics*
;
Female
;
Genotype
;
Heart Defects, Congenital/genetics*
;
Humans
;
Infant, Newborn
;
Polymorphism, Genetic
;
Pregnancy
;
Pregnancy Complications/drug therapy*
2.Changes of peripheral blood chromosomal centromere aberration in patients with cytomegalovirus infection after anti-viral treatment.
Lan GAO ; Yan-hui LIU ; Li-fen LI ; Ya-min WU ; Ming-bo WANG ; Jing SHI ; Bing YUAN ; Juan SONG ; Yong-ming HE ; Dai-kui WEI
Journal of Southern Medical University 2009;29(9):1846-1847
OBJECTIVETo study the changes of peripheral blood chromosomal centromere aberration in patents with cytomegalovirus (CMV) infection after anti-viral treatment.
METHODSSixty-two patients with early spontaneous abortion and CMV infection analyzed for their peripheral blood chromosomal centromere using simultaneous silver staining before and after anti-viral treatment.
RESULTSThe patients with CMV infection had high rate of centromere aberration, which was decreased significantly after anti-viral treatment (P<0.0001).
CONCLUSIONCMV infection is a risk factor for peripheral blood chromosomal centrimere aberration. Anti-viral treatment can decrease the rate of centrimere aberration aberration. Detection of peripheral blood chromosomal centrimere aberration allows the assessment of the severity of infection and the condition after treatment.
Abortion, Spontaneous ; blood ; genetics ; Adult ; Antiviral Agents ; therapeutic use ; Centromere ; genetics ; Chromosome Aberrations ; Cytomegalovirus Infections ; blood ; drug therapy ; genetics ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Infectious ; blood ; drug therapy ; genetics ; Young Adult
3.The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome.
Nada ARACIC ; Damir ROJE ; Ivana Alujevic JAKUS ; Marinela BAKOTIN ; Vedran STEFANOVIC
Yonsei Medical Journal 2016;57(5):1230-1235
PURPOSE: To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". MATERIALS AND METHODS: 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). RESULTS: There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ2=2.7; p=0.100) and LMWH treated pregnancies (χ2=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ2=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. CONCLUSION: The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended.
Adult
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Anticoagulants/*therapeutic use
;
Female
;
Heparin, Low-Molecular-Weight/*therapeutic use
;
Humans
;
Infant, Newborn
;
Polymorphism, Genetic
;
Pregnancy
;
Pregnancy Complications/*drug therapy/genetics
;
*Pregnancy Outcome
;
Thrombophilia/*drug therapy/genetics
;
Young Adult
4.The effect of maternal HBV DNA levels on HBV intrauterine transmission and fetal distress.
Jing WANG ; Tao Tao YAN ; Ya Li FENG ; Ying Li HE ; Yuan YANG ; Jin Feng LIU ; Nai Juan YAO ; Ya Ge ZHU ; Ying Ren ZHAO ; Tian Yan CHEN
Chinese Journal of Hepatology 2022;30(8):873-878
Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>106 IU/ml than those with HBV DNA <106 IU/ml (12.2% vs. 1.8%; χ2=11.275, P=0.006), and (24.4% vs. 16.0%, χ2=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>106 IU/ml than that of maternal HBV DNA<106 IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>106 IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral
;
Female
;
Fetal Distress/drug therapy*
;
Hepatitis B/prevention & control*
;
Hepatitis B Surface Antigens
;
Hepatitis B Vaccines/therapeutic use*
;
Hepatitis B virus/genetics*
;
Humans
;
Immunoglobulins/therapeutic use*
;
Infant
;
Infectious Disease Transmission, Vertical/prevention & control*
;
Placenta
;
Pregnancy
;
Pregnancy Complications, Infectious
5.Granulocyte Colony Stimulating Factor Attenuates Hyperoxia-Induced Lung Injury by Down-Modulating Inflammatory Responses in Neonatal Rats.
Ga Won JEON ; Dong Kyung SUNG ; Yu Jin JUNG ; Soo Hyun KOO ; Seo Heui CHOI ; Yun Sil CHANG ; Jong Beom SIN ; Won Soon PARK
Yonsei Medical Journal 2011;52(1):65-73
PURPOSE: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate hyperoxia-induced lung injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 microg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. RESULTS: This treatment significantly improved hyperoxia-induced reduction in body weight gain and lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67phox was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-beta. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 was not significant. CONCLUSION: In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.
Animals
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Animals, Newborn
;
Blotting, Western
;
Female
;
Granulocyte Colony-Stimulating Factor/*therapeutic use
;
Hyperoxia/*complications
;
In Situ Nick-End Labeling
;
Interleukin-6/genetics
;
Lung/*drug effects/*metabolism
;
Lung Injury/*drug therapy/etiology/genetics/metabolism
;
NADPH Oxidase/metabolism
;
Peroxidase/metabolism
;
Pregnancy
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Reverse Transcriptase Polymerase Chain Reaction
;
Transforming Growth Factor beta/genetics
;
Tumor Necrosis Factor-alpha/genetics
;
Weight Gain/drug effects