Fetal autonomic malfunction as a marker of fetal distress in growth-restricted fetuses: three case reports

Igor Victorovich Lakhno,Schmidt Alexander 대한산부인과학회 2019 Obstetrics & Gynecology Science Vol.62 No.6

Fetal growth restriction (FGR) is characterized by fetal compromise and delayed neurological maturation. We report3 cases of early FGR in the 26th week of gestation, based on hemodynamic Doppler monitoring, conventionalcardiotocography, and non-invasive fetal electrocardiography (NI-FECG). Fetal heart rate variability (HRV), beat-tobeatvariations, and fetal autonomic brain age scores (fABASs) were normal despite the absence of umbilical diastolicflow in the first case and the pregnancy continued to 30 weeks. NI-FECG helped achieve better fetal maturity. FetalHRV and fABASs were low in the second and third cases. Fetal demise occurred soon in both cases. We conclude thatNI-FECG could be a prospective method for the detection of fetal distress in early FGR.

중증 자간전증에서 태아 발육 지연 유무에 따른 모체 혈장 내 TNF - α 농도의 변화

김소라(So Ra Kim),이필량(Pil Ryang Lee),박진우(Jin Woo Park),정복경(Bok Kyung Jung),정지윤(Ji Youn Chung),원혜성(Hye Sung Won),이인식(In Sik Lee),김암(Ahm Kim) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

Objectives : The purposes of this study were to evaluate the possible role of Tumor necrotic factor-α(TNF-α) in development of preeclampsia, and to define the alteration of plasma TNF-α concentration in association with fetal growth restriction in preeclamptic women. Methods : Maternal blood samples were retrieved from 10 normal pregnancies, 10 pregnancies complicated with small for gestational age neonate of unknown cause, 10 preeclampsia with fetal growth restriction, and 10 preeclampsia without fetal growth restriction. The concentrations of TNF-α were measured by ELISA. Results : The plasma concentrations of TNF-α were significantly increased in preeclamptic women (p<0.05). However, there were no major differences in relation to fetal growth restriction. In idiopathic SGA group, the cytokine levels were significantly decreased compared to normal pregnancy (p<0.05). Conclusions : The increased concentrations of maternal plasma TNF-α in preeclamptic women suggest that preeclampsia may be an immunologic disorder. Though TNF-α influences on the fetal growth, it may not play a major role in the pathophysiology of fetal growth restriction in preeclampsia.

자궁내 태아 발육지연에서 신생아 예후의 산전예측인자: 태아 생물리학적 계수, 도플러검사, 태아 심박동 모니터의 효용성

송승은 ( Seung Eun Song ),서은성 ( Eun Sung Seo ),이수호 ( Su Ho Lee ),최석주 ( Suk Joo Choi ),오수영 ( Soo Young Oh ),노정래 ( Cheong Rae Roh ),김종화 ( Jong Hwa Kim ) 대한주산의학회 2009 Perinatology Vol.20 No.2

목적: 태아 발육지연에서 신생아 예후를 예측할 수 있는 산전 인자들을 알아보고 태아 안녕검사들 (태아 생물리학적 계수, 도플러검사, 태아 심박동 모니터)간의 일치도를 조사하였다. 방법: 임신 24주에서 33주 6일 사이에 분만한 자궁내 태아 발육지연 64예의 임신 결과 및 신생아 정보에 대해 후향성 조사를 하였다. 신생아 예후가 양호한 군과 불량한 군 간의 태아 안녕검사(태아 생물리학적 계수, 도플러검사, 태아 심박동 모니터)를 비롯한 산전 인자들을 비교하고 코헨의 카파값을 이용하여 태아 안녕검사 결과의 일치도를 평가하였다. 결과: 단변량 분석에서 불량한 신생아 예후와 관계 있는 산전 인자는 분만 시 임신 주수, 양수과소증, 비정상 정맥관 도플러였으나 다변량 분석에서는 분만 시 임신 주수와 양수과소증 만이 예후와 관계된 인자로 나타났다. 각각의 태아 안녕 검사의 일치도 검사 결과 태아 생물리학적 계수와 태아 심박동 모니터 결과만이 의미 있게 나타났다(카파값=0.303, P<0.019). 결론: 본 연구 결과, 34주 이전의 자궁내 태아 발육지연에서 시행되는 태아 안녕검사 즉, 태아 생물리학적 계수, 도플러검사, 태아 심박동 모니터 결과는 서로 일치하지 않는 경우가 상당히 있다는 점을 확인하였다. 따라서 어느 한 가지 태아 안녕검사에만 근거하여 태아 발육지연의 분만시점을 결정하기 보다는 세 가지 검사를 종합하여 분만 시점을 결정하는 것이 권장되며 특히 임신 주수와 양수 과소증 유무를 최우선으로 고려한 신중한 분만시기의 결정이 중요할 것으로 판단된다. Purpose: To identify the antenatal variables predictive of neonatal outcome and to examine the relationship between biophysical score, multivessel Doppler ultrasound and fetal heart rate monitoring in fetal growth restriction (FGR). Methods: We retrospectively analyzed the pregnancy and neonatal outcomes of 64 growth restricted fetuses delivered at less than 34 weeks of gestation at Samsung Medical Center, from May 2005 to May 2008. The result of Doppler velocimetry including umbilical artery, middle cerebral artery, and ductus venosus and biophysical score (BPS) and fetal heart rate (FHR) monitoring for each subject were reviewed. Adverse neonatal outcome was defined as bronchopulmonary dysplasia, periventricular leukomalacia, grade 3~4 intraventricular hemorrhage, grade 3~4 retinopathy of prematurity, necrotizing enterocolitis, neonatal sepsis, and perinatal mortality. We performed the univariate and multivariate analysis to determine which antenatal fetal surveillance test is the best to predict the adverse neonatal outcome in preterm FGR. We also assessed the degree of agreement of each antenatal test by the Cohens kappa test. Results: By the univariate analysis, significant variables associated with adverse neonatal outcome were gestational age at delivery, oligohydramnios, and abnormal ductus venosus Doppler. However, in the multivariate analysis, gestational age at delivery and oligohydramnios remained as independent predictors of adverse neonatal outcome. Degree of agreement among the antenatal tests expressed by the Cohens kappa was only significant between BPS and FHR monitoring (kappa=0.303, P=0.019). Conclusion: Our data suggests that the timing of delivery of growth restricted fetuses less than 34 weeks of gestation should be determined by the gestational age and oligohydramnios, not by the one abnormal antenatal fetal surveillance result. We also confirmed that there are considerable amount of disagreements among BPS, mutivessel Doppler, and FHR monitoring.

태아발육지연 임신과 정상 성장 임신 태반에서의 BRCA1 유전자 발현 양상에 관한 연구

문종수(JS Moon),정재현(JH Jeong),박창수(CS Park),양순하(SH Yang),노정래(JR Roh),송상용(SY Song) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.6

Objective: BRCA1, the breast and ovarian cancer susceptibility gene, is regarded as not only a tumor suppressor gene but regulator of cell growth and differentiation. We hypothesized that there is a relationship between BRCA1 expression and growth and differentiation of trophoblast. Methods: Twenty placental samples were collected from 5 fetal growth-restricted term pregnancies and 15 normal growth pregnancies at different gestational ages [from 9th week of gestational age to term ; 5 samples from each trimester]. Immunohistochemistry and western blotting were performed for identifying the expression of BRCA1 protein. Results: The expression of BRCA1 were detected on all normal placentas. We could not find any remarkable difference of BRCA1 expression according to gestational age on normal placentas. In growth-restricted placenta, the staining intensity was diminished more than 30% and the number of stained cells were decreased more than 20% by immunohistochemistry, and BRCA1 protein expression was decreased about 30% on western blotting compared with normal placenta. Conclusion: These results revealed that the expression of BRCA1 gene is a constant finding irrespective of gestational ages and decreased in the placenta taken from growth restricted fetuses compared with normal fetuses. It suggests that BRCA1 may play a role in trophoblast differentiation and be related to the pathophysiologic mechanism of fetal growth restriction.

자간전증 산모에서 제대정맥 혈청Nitric oxide 농도와 태아 성장지연과의 관계

차문석(Moon Seok Cha) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

Objective: To evaluate the role of nitric oxide(NO) in fetal growth. Method: We measured umbilical vein serum NO in preeclampsia by Stuehr method and evaluated the association with the fetal birth weight and compared with normal pregnancy and twin pregnancy. Results: 1. The umbilical vein serum nitrite concentration in preeclampsia was higher than that of the normal pregnancy (p<0.005). 2. Umbilical vein serum nitrite concentration of FGR(fetal growth restriction) baby group was higher than that of the non-FGR group in preeclampsia (p<0.005). 3 Umbilical vein serum nitrite concentration of larger baby group was higher than that of the smaller baby group in twin pregnancy but statistically not significant (p>0.005). 4. There were no significant differences of umbilical vein serum nitrite concentration between twin pregnancy and normal single pregnancy group (p>0.005). Conclusion: These results suggest that the increased nitric oxide production in the umbilical vein may be a compensatory response to improve blood flow and fetal growth in preeclampsia.

The Gut Microbiota of Pregnant Rats Alleviates Fetal Growth Restriction by Inhibiting the TLR9/MyD88 Pathway

Tang Hui,Li Hanmei,Li Dan,Peng Jing,Zhang Xian,Yang Weitao 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.9

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

태아발육제한 처치의 최신지견

김종운 ( Jong Woon Kim ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.1

Fetal growth restriction (FGR) is one of the most common and complex diseases and it is associated with increased perinatal mortality and morbidity. FGR influences the long-term health of neonates and their offspring. The aim of obstetric management is to identify growth-restricted fetuses at risk of severe intrauterine hypoxia, to monitor their health and to deliver when the adverse outcome is imminent. This review aims to investigate the new aspects of FGR including the diagnosis, antenatal surveillance, and clinical management.

발육제한 태아에서 placental ratio 와 신생아 이환률과의 관계

이준희(Jun Hee Lee),정인배(In Bai Chung),이영심(Young Sim Lee),최중호(Jung Ho Choi),이정렬(Jeong Yel Lee),한혁동(Hyuck Dong Han),이영진(Young Jin Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

An increased placental ratio has known to be associated with the occurrence of cardiovascular complications in adulthood among the intrauterine fetal growth restriction. A retrospective study on 202 singleton growth-restricted infants without major congenital anomalies born from Jan. 1995 to Feb. 2001 was performed to determine the relationship between placental ratio and neonatal morbidity. The cases were categorized into three groups according to the placental ratio (<1SD below the mean, within 1SD of the mean, >1SD above the mean). There were no differences in the maternal characteristics and antenatal complications except pregnancy induced hypertension between high placental ratio group and the other groups. It presented the trend that was toward the increase of placental weight and the decrease of birth weight in high placental ratio group. The infants with a high placental ratio had increasing tendencies of meconium stained amnionic fluid, hypocalcemia, phototherapy, asphyxia.

Fetal growth changes and prediction of selective fetal growth restriction following fetoscopic laser coagulation in twin-to-twin transfusion syndrome

So Yeon Kim,Hye-Sung Won,Mi-Young Lee,Jin Hoon Chung,Jin-Hee Park,You-Kyoung Kim,Hwang-Mi Lee 대한산부인과학회 2023 Obstetrics & Gynecology Science Vol.66 No.6

Objective To investigate fetal growth changes and predictive factors for selective fetal growth restriction (sFGR) in patients with twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser coagulation (FLC). Methods This retrospective study included twin-pregnant women with fetal TTTS who underwent FLC at our institution between 2011 and 2020. Twin pairs who survived at least 28 days after FLC and at least 28 days after birth were included. A paired t-test was used to compare the mean discordance between the estimated fetal weights at the FLC and the birth weights. The predictive factors for sFGR after FLC were evaluated using univariate and multivariate logistic regression analyses. Results A total of 119 eligible pairs of patients who underwent FLC were analyzed. The weight percentile at birth significantly decreased after FLC in the recipients (53.7±30.4 percentile vs. 43.7±28.0 percentile; P<0.001), but increased in the donors (11.5±17.1 percentile vs. 20.7±22.8 percentile; P<0.001). Additionally, the mean weight discordance of twin pairs significantly decreased after FLC (23.9%±12.7% vs. 17.3%±15.7%; P<0.001). After FLC, Quintero stage ≥3, pre-FLC sFGR, abnormal cord insertion, and post-FLC abnormal umbilical artery Doppler (UAD) were all significantly higher in the sFGR group than the non-sFGR group. The prediction model using these variables indicated that the area under the receiver operating characteristic curve was 0.898. Conclusion The recipient weight percentile decreased, whereas donor growth increased, resulting in reduced weight discordance after FLC. The Quintero stage, pre-FLC sFGR, and post-FLC abnormal UAD were useful predictors of sFGR after FLC in TTTS.

최신임상강좌 : 태아발육지연 처치의 최신 지견

김영한 ( Young Han Kim ),곽동욱 ( Dong Wook Kwak ) 대한산부인과학회 2008 Obstetrics & Gynecology Science Vol.51 No.10

Small-for-gestational-age (SGA) is associated with poor perinatal outcomes. The term SGA is descriptive and means that the fetal size and weight at birth are less than expected (in general, 10th percentile using standard curves for gestational age) regardless of the cause. It was estimated that about 50~70% of fetuses born weighing less than the 10th percentile for gestational age are constitutionally small, with fetal growth appropriate for parental size and ethnicity; these are usually associated with normal placental function and have a normal outcome. Fetal growth restriction (FGR) describes a decrease in the fetal growth rate that prevents an infant from obtaining the complete genetic growth potential. It is common with placental dysfunction occurring in about 3% of pregnancies despite advances in obstetric care. In human pregnancies, placental insufficiency is the leading cause of FGR and is usually due to poor utero-placental blood flow and placental infarcts. The reduction of placental supply of nutrients to the fetus has been associated with several adaptive changes taking place in both the placenta and fetus. Adaptive changes can be followed by pathology leading to fetal death, and therefore staging of the disease is fundamental to timing delivery. Thus, it is responsible for the obstetricians to distinguish SGA from intrauterine growth restriction, correct the causes if possible, and if not, accurately stage the disease progress so as to deliver at the most suitable time. In this review, the management of fetal growth restrictions is summarized based on the diagnosis, etiologic factors, antenatal surveillance, and their possible therapeutic approaches.