Tanshinone IIA increased amniotic fluid volume through down-regulating placental AQPs expression via inhibiting the activity of GSK-3ß.

The mechanism of idiopathic oligohydramnios is still uncertain, and there is no effective and targeted treatment for it. Placental aquaporins (AQPs) were associated with idiopathic oligohydramnios. This study aimed to investigate the effect of tanshinone IIA on amniotic fluid volume (AFV) and its underlying molecular mechanisms related to placental AQPs (AQP1, AQP3, AQP8, AQP9). Results showed that compared with the women with normal AFV, placental AQP1, AQP3, AQP8, and AQP9 protein expressions were decreased in women with idiopathic oligohydramnios. Immunohistochemistry revealed localization of AQP1, AQP3, AQP8, and AQP9 mainly in trophoblast cells within labyrinth zone of mouse placenta. Also, AQP1 was located in fetal vascular endothelial cells. Pregnant mice were administered with tanshinone IIA (10 mg/kg or 50 mg/kg, n = 8, respectively) or vehicle (n = 8) from 9.5 to 18.5 gestational day (GD). Tanshinone IIA markedly increased the AFV in pregnant mice, without the effects on embryo numbers per litter, atrophic embryo rate, fetal weight, and placental weight, as well as increased the expressions of AQPs and inhibited the activity of GSK-3ß in mice placenta. In JEG-3 cells, tanshinone IIA downregulated AQP1, AQP3, AQP8, AQP9 expressions and inhibited the activity of GSK-3ß. Activating GSK-3ß with MK-2206 eliminated these alterations. Thus, tanshinone IIA could increase AFV in pregnant mice, possibly through downregulating placental AQP1, AQP3, AQP8, and AQP9 expression via inhibiting the activity of GSK-3ß. Tanshinone IIA may be optional for the treatment of idiopathic oligohydramnios.

Associations between prepregnancy body mass index, gestational weight gain, and pregnancy outcomes in women with twin pregnancies: A five-year prospective study.

BACKGROUND: The purpose of this project was to investigate the relationship between prepregnancy body mass index (ppBMI), gestational weight gain (GWG), and pregnancy outcomes in women with twin pregnancies. METHODS: A prospective cohort of 369 women with dichorionic diamniotic twin pregnancies was recruited from 2016 to 2020. According to ppBMI using Chinese BMI classifications, they were categorized into the underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-23.9 kg/m2 ), and overweight and obese (BMI ≥ 24 kg/m2 ) groups. In each ppBMI group, they were divided into two subgroups based on the presence or absence of the complications such as gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and small for gestational age (SGA). The outcomes including GDM, HDP, and SGA were compared among three ppBMI groups, and the associations of GWG with these outcomes within each ppBMI category were analyzed. RESULTS: Twin-pregnant women with overweight and obesity were at increased risks of HDP (aOR = 4.417 [95% CI = 1.826-9.415]) and SGA (2.288 [1.102-4.751]), whereas underweight women were prone to deliver SGA newborns (2.466 [1.157-5.254]). Women with GDM gained less weight during pregnancy than those without GDM within each ppBMI category. For overweight and obese women, greater GWG increased the incidence of HDP (1.235 [1.016-1.500]) and decreased the risk of SGA (0.818 [0.702-0.953]). CONCLUSIONS: Both ppBMI and GWG in twin-pregnant women were strongly associated with HDP and SGA, but not GDM.

Effect of later cord clamping on umbilical cord blood gas in term neonates of diabetic mothers: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of later cord clamping (LCC) on umbilical arterial blood gas in neonates of diabetic mothers. METHODS: This prospective study included a group of 160 diabetic mothers (DM) whose neonates were randomized to immediate cord clamping (ICC) (≤ 15 s after birth) or LCC (≥ 30 s after birth), and a group of 208 non-diabetic mothers (NDM) whose neonates were randomized to ICC or LCC as a reference. Cord arterial pH, base excess (BE), bicarbonate (HCO3-), partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), lactate, hemoglobin, hematocrit and glucose were compared among groups. RESULTS: In neonates of DM, there was no significant difference in cord arterial pH between the ICC and LCC group. LCC of ≥ 30 s decreased umbilical arterial HCO3- and BE and increased lactate (ICC versus LCC, HCO3-: 24.3 (22.7, 25.8) versus 23.7 (22.3, 24.7) mmol/L, P = 0.01; BE: -2.70 (-4.80, -1.50) versus - 3.72 (-5.66, -2.36) mmol/L, P = 0.006; lactate: 2.1 (1.6, 3.7) versus 2.7 (2.1, 4.3) mmol/L, P = 0.005), without the alterations of pCO2, pO2, hemoglobin, hematocrit and glucose. Similar results were found in neonates of NDM (ICC versus LCC, HCO3-: 24.3 (23.1, 25.7) versus 23.5 (22.3, 24.8) mmol/L, P = 0.01; BE: -2.39 (-3.73, -1.51) versus - 3.40 (-4.73, -1.91) mmol/L, P = 0.001; lactate: 2.2 (1.9, 3.3) versus 2.5 (2.0, 4.3) mmol/L, P = 0.01), except for the higher level of hemoglobin in the LCC group. The majority of diabetic mothers (ICC: 92.0%; LCC: 91.8%) had good blood glucose control. No differences were observed in acid-base status and glucose between neonates of DM and neonates of NDM in both ICC and LCC, but hemoglobin and hematocrit were elevated after ICC in neonates of DM compared to neonates of NDM. CONCLUSIONS: Later cord clamping of ≥ 30 s resulted in a tendency towards metabolic acidosis of umbilical arterial blood in neonates of DM and NDM. Umbilical arterial blood gas parameters at birth were similar in neonates of DM and NDM. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04369313 ; date of registration: 30/04/2020 (retrospectively registered).

Effect of delayed cord clamping on jaundice and hypoglycemia in the neonates of mothers with gestational diabetes mellitus.

OBJECTIVE: To study the effect of delayed cord clamping (DCC) on the bilirubin levels and hypoglycemia in neonates with diabetic mothers (NDMs). METHODS: This is a comparison between a prospective cohort and a historical control cohort. Women with gestational diabetes mellitus who performed DCC were enrolled into the prospective cohort (n = 156), and those who performed early cord clamping (ECC) were enrolled into the historical control cohort (n = 161). RESULTS: NDMs who received DCC had higher transcutaneous bilirubin than those in the ECC group whether maternal glycemic control was good or poor. DCC increased the rate of neonatal hyperbilirubinemia and phototherapy when maternal blood glucose was well controlled but not when it was poorly controlled. No differences were found in initial blood glucose levels on days 1 to 3 of life between the two groups. CONCLUSION: Delayed cord clamping increased bilirubin levels, the risk of neonatal hyperbilirubinemia, and phototherapy in IDMs without improved initial blood glucose levels. Therefore, DCC was not recommended in NDMs.

The association of antenatal D-dimer and fibrinogen with postpartum hemorrhage and intrauterine growth restriction in preeclampsia.

BACKGROUND: D-dimer and fibrinogen were verified to be altered in preeclampsia. This study was to evaluate the associations of D-dimer and fibrinogen plasma levels with postpartum hemorrhage or intrauterine growth restriction in preeclamptic women. METHODS: This was a retrospective study that recruited 278 preeclamptic women with singleton pregnancy from January 2016 to December 2019. Patients were allocated into five groups: mild preeclampsia (mPE) (n=68), mild preeclampsia with postpartum hemorrhage (mPE+PPH) (n=13), severe preeclampsia (sPE) (n=112), severe preeclampsia with postpartum hemorrhage (sPE+PPH) (n=17) and severe preeclampsia with intrauterine growth restriction (sPE+IUGR) (n=68). The antenatal D-dimer and fibrinogen plasma levels were analyzed among the groups. Logistic regression was used to determine the correlation between serum indexes and PPH or IUGR in preeclampsia. RESULTS: The antenatal D-dimer plasma levels were significantly higher in the sPE+PPH group than that in the sPE group (2.02 µg/ml versus 1.37 µg/ml, P = 0.001), but there was no difference in fibrinogen. Elevated D-dimer was associated with PPH among severe preeclamptic women (adjusted odds ratio (aOR) [95% CI]: 3.093 [1.527-6.264], P = 0.002). No differences in D-dimer and fibrinogen were found between the mPE and mPE+PPH groups or between the sPE and sPE+IUGR groups. CONCLUSIONS: Elevated antenatal plasma D-dimer level may be associated with postpartum hemorrhage in severe preeclampsia, but not with intrauterine growth restriction. Future prospective clinical trials are needed to investigate the predictive value of D-dimer in postpartum hemorrhage in severe preeclampsia.

Effects of delayed cord clamping on neonatal jaundice, phototherapy and early hematological status in term cesarean section.

BACKGROUND: Delayed cord clamping in full-term neonates is widely recommended, while in practice, it is rarely implemented in cesarean section due to the fear of neonatal jaundice and excessive maternal blood loss. The optimal timing of cord clamping remains uncertain. This study was to fully evaluate the effects of delayed cord clamping on short-term hematological status and jaundice in term neonates delivered by cesarean section. METHODS: This retrospective study enrolled 796 women, who were allocated into the early cord clamping group (n = 377) and the delayed cord clamping group (n = 419). The latter group was further divided into two subgroups (30-60 s, 61-120 s). The outcomes were neonatal transcutaneous bilirubin levels on 0 to 5 days of life and the rate of phototherapy. For neonates who had blood tests on the first three days of life, their hemoglobin and hematocrit were compared among groups. RESULTS: Compared with the early cord clamping group, delayed cord clamping merely increased the transcutaneous bilirubin level of neonates on the day of birth rather than that on the following five days. The heel peripheral blood sample size of 1-3 days in the early cord clamping group was 61, 25 and 33, and in the delayed cord clamping group was 53, 46 and 32, respectively. Delayed cord clamping at 30-60 s resulted in the higher neonatal hemoglobin level on day 3 and an increased rate of neonatal polycythemia, without a higher rate of phototherapy. Delayed cord clamping beyond 60 s did not further improve hematological status in term neonates born by cesarean section. CONCLUSION: In cesarean section, delayed cord clamping for 30-60 s improved the early hematological status of term neonates without the enhanced requirement of phototherapy for neonatal jaundice.

Expression and Regulation of Aquaporins in Pregnancy Complications and Reproductive Dysfunctions.

Aquaporins (AQPs), small hydrophobic integral membrane proteins, mediate rapid transport of water and small solutes. The abnormal expressions of AQPs are associated with pregnancy complications and reproductive dysfunctions, including preeclampsia, gestational diabetes mellitus, tubal ectopic pregnancy, intrahepatic cholestasis of pregnancy, preterm birth, chorioamnionitis, polyhydramnios, and oligohydramnios, thus resulting in adverse pregnancy outcomes. This review explains the alterations of AQPs in pregnancy complications and reproductive dysfunctions and summarizes the molecular mechanisms involved in the regulations of AQPs by drugs such as oxytocin, polychlorinated biphenyls, all-trans-retinoic acid, salvia miltiorrhiza, and insulin, or other factors such as oxygen and osmotic pressure. All the research provides evidence that AQPs could be the new therapeutic targets of pregnancy-related diseases.

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring.

Phthalates are a group of ubiquitous synthetic endocrine-disrupting chemicals. Fetal and neonatal periods are particularly susceptible to endocrine disorders, which prenatal exposure to phthalates causes. There is increasing evidence concerning the potential endocrine disrupting for phthalate exposure during pregnancy. This article aims to review the endocrine impairment and potential outcomes of prenatal phthalate exposure. Prenatal exposure phthalates would disrupt the levels of thyroid, sex hormone, and 25-hydroxyvitamin D in pregnant women or offspring, which results in preterm birth, preeclampsia, maternal glucose disorders, infant cryptorchidism, infant hypospadias, and shorter anogenital distance in newborns, as well as growth restriction not only in infants but also in early adolescence and childhood. The relationship of prenatal phthalate exposure with maternal and neonatal outcomes in human beings was often sex-specific associations. Because of the potentially harmful influence of prenatal phthalate exposure, steps should be taken to prevent or reduce phthalate exposure during pregnancy.

Timing of umbilical cord clamping and neonatal jaundice in singleton term pregnancy.

BACKGROUND: Delayed cord clamping was not adopted widely in China because of the potential effect of neonatal hyperbilirubinemia, jaundice and polycythemia, and the optimal cord clamping time remained controversial. AIM: To assess the effect of delayed cord clamping versus early cord clamping on neonatal jaundice for term infants. STUDY DESIGN: This retrospective study included 1981 mother-infant pairs, who were assigned to early cord clamping groups (n = 1005) and delayed cord clamping group (n = 949). The delayed cord clamping included three subgroups (30-60 s, 61-90 s, 91-120 s). The main outcomes were transcutaneous bilirubin levels at 0 to 4 days of age, the rate of jaundice requiring phototherapy, the neonatal hematological status at 1 to 3 days after birth. RESULTS: Compared with the early cord clamping group, the neonatal transcutaneous bilirubin level did not differ and the neonatal hematological status (hemoglobin and hematocrit levels) were improved in combined and three subgroups of delayed cord clamping group. Increasing the duration of cord clamping from 90 s to 120 s did not result in further increases in hemoglobin and hematocrit levels but led to a trend towards a higher risk of neonatal jaundice requiring phototherapy and neonatal polycythemia. CONCLUSIONS: Delayed cord clamping for <90 s in healthy term infants may not only improve the early hematological status of newborns but also avoid excessive neonatal jaundice requiring phototherapy.