Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy ; Female ; Humans ; Placenta ; Fetal Growth Retardation/etiology* ; Pre-Eclampsia/pathology* ; Reactive Oxygen Species ; Hypoxia/pathology* ; Pregnancy Complications/pathology* ; Endoplasmic Reticulum Stress

OBJECTIVES: To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. METHODS: A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value. CONCLUSIONS Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.
Asphyxia/complications* ; Child ; Enterocolitis, Necrotizing/etiology* ; Female ; Fetal Growth Retardation ; Humans ; Hypoalbuminemia ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases/etiology* ; Nomograms ; Sepsis/complications*

Objective: To explore the risk factors for different types of hypospadias. METHODS: According to the 1∶1 ratio, we included hypospadias children in the case group and those without urinary abnormality as controls, all from the Third Affiliated Hospital of Zhengzhou University between October 2015 to October 2016. Using univariate and multivariate logistic regression analyses, we investigated the risk factors for hypospadias as well as for four different types of the disease. RESULTS: Among the 440 subjects, the risk factors for hypospadias included preterm birth, fetal growth restriction, rural residence of the mother, pregnancy age <20 or >35 years, primipara, maternal smoking (including passive smoking), oral progesterone, cold or fever during pregnancy, and exposure to high temperature in early pregnancy, while the protective factors included protein supplement in early pregnancy. The pregnancy age <20 or >35 years was the main risk factor for type I hypospadias; preterm birth, fetal growth restriction, rural residence of the mother, primipara, and maternal smoking (including passive smoking) during pregnancy were the risk factors for type Ⅱ; preterm birth, fetal growth restriction, rural residence of the mother, and exposure to high temperature in early pregnancy were those for type Ⅲ; and exposure to high temperature in early pregnancy and oral progesterone during pregnancy were those for type Ⅳ. CONCLUSIONS The risk factors for hypospadias vary for different types, and therefore hypospadias-related clinical studies should be conducted and preventive measures should be taken accordingly. However, a larger sample size is needed to get more scientific and reliable results concerning the risk factors for different types of hypospadias.
Adult ; Female ; Fetal Growth Retardation ; Humans ; Hypospadias ; classification ; etiology ; Infant, Newborn ; Male ; Maternal Age ; Pregnancy ; Premature Birth ; Regression Analysis ; Risk Factors ; Rural Population ; Smoking ; Young Adult

OBJECTIVETo study the incidence and risk factors for extrauterine growth retardation (EUGR) at discharge in premature infants.

METHODSA retrospective analysis was performed on 596 premature infants who were admitted to the neonatal intensive care unit between 2006 and 2010. These subjects were classified into EUGR (n=217) and non-EUGR groups (n=379) based on the body weight at discharge. The risk factors for the occurrence of EUGR were studied by multivariate logistic regression analysis.

RESULTSBased on the body weight, length, and head circumference, the incidence of EUGR at discharge was 36.4% (217 cases), 42.0% (250 cases), and 22.8% (136 cases), respectively. Low gestational age, low birth weight, intrauterine growth retardation (IUGR), delayed enteral feeding and complications of the respiratory system were identified as risk factors for EUGR (OR=6.508, 14.522, 5.101, 1.366, and 1.501, respectively).

CONCLUSIONSThe incidence of EUGR might be greatly decreased by strengthening the perinatal care, reducing the incidence of premature delivery and IUGR, undertaking early enteral feeding, and actively preventing postnatal complications.

Female ; Fetal Growth Retardation ; epidemiology ; etiology ; Humans ; Infant, Newborn ; Infant, Premature ; Logistic Models ; Male ; Retrospective Studies ; Risk Factors

Embryonic diapauses mean that early embryos stop developing for some reasons in early pregnant stage. The embryo has dead in uterine cavity, but has not yet discharged. The early clinical manifestation in the areas of traditional Chinese medicine (TCM) can be classified as "pregnant vaginal bleeding", "fetal irritability" and other diseases. Embryonic diapause is a common and difficult gynecologic clinical disease. The prevalence rate which is increasing has become a major reproductive health problem. So the prevention research of embryonic diapauses is very significant. In this paper, through the induction and the summary of Chinese and Western medicine dynamic researches and control methods of embryonic diapauses, detailing a list of pathogenesis and treatment progress in embryonic diapauses. Besides, it can lay the foundation for further study and reducing embryonic diapauses incidence, which can promote reproductive health development.
Fetal Growth Retardation ; etiology ; metabolism ; prevention & control ; psychology ; Humans ; Medicine ; methods ; Medicine, Chinese Traditional ; methods ; Western World

Recent advances in dialysis and a multidisciplinary approach to pregnant patients with advanced chronic kidney disease provide a better outcome. A 38-yr-old female with autosomal dominant polycystic kidney disease (ADPKD) became pregnant. She was undergoing hemodialysis (HD) and her kidneys were massively enlarged, posing a risk of intrauterine fetal growth restriction. By means of intensive HD and optimal management of anemia, pregnancy was successfully maintained until vaginal delivery at 34.5 weeks of gestation. We discuss the special considerations involved in managing our patient with regard to the underlying ADPKD and its influence on pregnancy.
Adult ; Female ; Fetal Growth Retardation/etiology ; Humans ; Kidney Failure, Chronic/therapy ; Polycystic Kidney, Autosomal Dominant/*diagnosis ; Pregnancy ; Renal Dialysis ; Risk Factors ; Tomography, X-Ray Computed

Interactions of vascular endothelial growth factor (VEGF) with receptors VEGFR1/Flt1 and VEGFR2/Flk1, and those of angiopoietins (Ang-1, Ang-2) with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation (D15, D18 and D21). The rats were randomly assigned into 3 groups: normal group, model group [fetal growth restriction (FGR) model], and Bushen Yiqi Huoxue (BYHR) recipe treatment group (BYHR group, the pregnant rats with FGR were treated with BYHR recipe). Morphological analysis indicated that during initial villous formation, fetal nucleated erythrocytes (FNEs) appeared in maternal blood sinus (MBS). Subsequently, FNEs were surrounded by endothelial cells to form fetal capillary (FC) and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining (EIS) in normal and BYHR groups. Whereas, villous formation was suppressed, normal increase in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flk1 mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while decreased on D21 in model group as compared with normal group and BYHR group. Immunohistochemically, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fetal Growth Retardation ; etiology ; physiopathology ; therapy ; Male ; Neovascularization, Physiologic ; drug effects ; physiology ; Placenta ; blood supply ; drug effects ; physiopathology ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Tobacco Smoke Pollution ; adverse effects

Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values: 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These results suggest that the offspring of AT1-Ab-positive pregnant rats are more susceptible to vascular functional abnormality while being fed high-salt diet.
Animals ; Antibodies ; blood ; Cardiovascular Diseases ; etiology ; physiopathology ; Disease Susceptibility ; Female ; Fetal Growth Retardation ; physiopathology ; Immunization ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; immunology ; Sodium Chloride, Dietary ; administration & dosage ; adverse effects

OBJECTIVETo study the role of promoter methylation of insulin-like growth factor binding protein 3 (IGFBP3) in intrauterine growth restriction (IUGR).

METHODSFifty neonates with IUGR and 30 healthy neonates were enrolled. The promoter methylation status of IGFBP3 in peripheral blood was evaluated by methylation-specific PCR (MSP) and high resolution melting (HRM) techniques.

RESULTSThe complete methylation rate, partial methylation rate and non-methylation rate of IGFBP3 promoter in the IUGR group was 4% (2/50), 40% (20/50) and 56% (28/50), respectively. The partial methylation rate and non-methylation rate of IGFBP3 promoter in the control group were 13% (4/30) and 87% (26/30), respectively. There were significant differences in the promoter methylation rate of IGFBP3 between the two groups (P<0.01).

CONCLUSIONSThe promoter methylation of IGFBP3 gene is associated with the pathogenesis of IUGR.

DNA Methylation ; Female ; Fetal Growth Retardation ; etiology ; genetics ; Humans ; Infant, Newborn ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; Male ; Promoter Regions, Genetic

AIMTo inspect the effects of cold-stress on filial growth and development of pregnant mice.

METHODSPregnant mice were divided into pregnant control group(PN) and pregnant cold-stress group (PC). The PC were kept in (4 +/- 2) C from 8:00 to 12:00 every day and the PN were kept in 25 degrees C. After 18 days, the blood pressure of pregnant mice were measured, and the weight of fetus, placenta and amniotic fluid were recorded. The natal mice visceral organs weight, visceral organs weight and body weight ratio were also measured. Growth curve and increment ratio curve of body weight were protracted every day from 1 st day to 44th day. Blood pressure of all filiality were measured in 8 weeks after they were born.

RESULTSThe blood pressure in PC was increased than that in PN (P < 0.05), the weight of fetus, placenta and amniotic fluid of PC decreased significantly compared with PN (P < 0.01). The filial visceral organ weight of PC reduced obviously compared with PN (P < 0.05), while the visceral organs weight and body weight ratio had no statistical meanings between the offspring of PC and PN (P > 0.05). Obvious difference of growth curve of the two filial groups was also existed until sexual maturity, but increment ratio curve of body weight of the two filial groups was basically fitted close. Filial blood pressure of PC was evidently higher than that in PN.

CONCLUSIONCold-stress stimulations seriously affect filial growth and development of pregnant mice.

Animals ; Cold Temperature ; adverse effects ; Female ; Fetal Growth Retardation ; etiology ; Hypertension, Pregnancy-Induced ; etiology ; Male ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; Stress, Physiological ; physiology