The original author of this article: Qi Lei, published in: Linyao.com
What is fetal growth restriction ?
Fetal growth restriction (FGR) means that the fetus is affected by various factors and fails to reach its expected growth potential. The main manifestation is that the birth weight is below the 10th percentile of the weight of the same gestational age or two standard deviations below the average birth weight [1].
Fetal growth restriction (FGR) is a common complication in clinical obstetrics. The incidence in the United States and Europe is 5%-15%, and the incidence in developing countries is 10%～ 55%. Reports on the incidence of FGR in my country are different, ranging from 6.39% to 9.4%, which is very unfavorable to the normal growth and development of the fetus. In severe cases, it can lead to perinatal death. At present, the clinical treatment of fetal growth restriction mainly uses conventional drugs, such as injections of glucose, amino acids, Ringers, vitamins, and Danshen injections. Although they can achieve certain effects, they are not effective in improving the biophysical score of the fetus. Therefore, what kind of drugs to take to treat fetal birth limitation has become a hot spot in the clinical research of obstetrics . According to reports, the key to treatment of fetal growth restriction is to improve the hypercoagulable state of blood during pregnancy and promote placental blood circulation, so as to ensure the normal growth and development of the fetus. The low-molecular-weight heparin belongs to the widely used anticoagulant , which has strong anticoagulant and blood viscosity reduction effects, and can effectively inhibit Xa activity. It is very effective in fetal growth restriction[2] .
FGR not only affects the growth and development of the fetus, but also extends the risk to the fetus after birth, resulting in impaired physical and intellectual development in adolescence, and some may even develop cerebral palsy after adulthood. The prevalence of compensatory diseases is increasing. Therefore, preventing and reducing the occurrence of FGR is for improving neonatal prevention,Improving the quality of the birth population is extremely important [3].
Factors related to the occurrence of fetal growth restriction
Pregnant women's poor living habits, harmful environmental factors, umbilical cord factors, pregnancy complications, genetic factors, etc. are all related factors of FGR. See Table 1 [3] for details.
Table 1
Bad lifestyle habits include smoking, alcohol and drug abuse and other bad lifestyle habits that can lead to the occurrence of FGR. Harmful environmental factors such as teratogenic chemicals, toxic, radioactive substances, high-decibel noise, electromagnetic radiation and severe air and environmental pollution will have an adverse effect on the development of the fetus and greatly increase the probability of birth of a deformed child. Obstacles to the blood circulation of the umbilical cord due to various reasons before birth can lead to hypoxia and affect the growth and development of the fetus. Pregnant women with pregnancy-induced hypertension , cardiopulmonary disease, anemia, chronic nephritis, amniotic fluid, etc. are also prone to FGR. The whole process of fetal growth and development is controlled by genes. 40% of the difference in fetal birth weight comes from genetic factors, especially maternal genetic and environmental factors. About 17% of FGR fetuses have chromosomal abnormality . Such as sex chromosome abnormalities, chromosomal imbalances, etc., especially in people with trisomy 13, 18, 21, FGR often appears earlier.
Low molecular weight heparin for fetal growth restriction Research object. They were randomly divided into observation group (n=30) and control group (n=30) by lottery. The control group was treated with conventional methods (symptomatic treatments such as amino acids, vitamins, Ringer's rehydration), and the observation group was treated with low-molecular-weight heparin on the basis of the control group. To observe and compare the weekly uterine height growth of the two groups of pregnant women and the weekly development of the fetus, and compare the occurrence of adverse perinatal outcomes between the two groups. turn out,The observation group's fetal head circumference, abdominal circumference, double parietal diameter, femoral diameter, and pregnant women’s weekly uterine growth value were significantly higher than those of the control group (P＜0.05); and the observation group’s incidence of premature infants, neonatal asphyxia rate, and acute fetus The distress rate and the incidence of term low birth weight infants were significantly lower than those of the control group (P<0.05).> published in J Perinatol in 2020 entitled "Pregnant low molecular weight heparin and sildenafil citrate in the treatment of fetal growth restriction: a randomized, parallel grouping, open-label clinical trial" [4] compared citrate The effects of sildenafil and low-molecular-weight heparin on neonatal birth weight and fetal placental blood flow in FGR pregnant women.
From June 2017 to September 2018, a parallel grouping, randomized clinical trial was conducted, involving 100 pregnant women with placental-mediated FGR between 28 and 35 weeks of gestation. They were randomly assigned to receive SC or LMWH from the diagnosis of FGR until delivery.
108 women were assessed as qualified, 6 were unqualified, and 2 refused to participate in the study. 100 pregnant women were randomly divided into sildenafil group (n=50) and low molecular weight heparin group (n=50). All patients were hospitalized and showed adherence to treatment. All 100 pregnant women completed the study (Figure 1):
Figure 1
There was no statistical difference in baseline characteristics between the two groups (Table 2):
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Table 2 There is a significant difference between the average EFW of the two components of
during delivery (1635.7±192.8g in the low molecular weight heparin group and 1430.2±239.1g in the sildenafil group); similarly, the average increase in fetal weight during the treatment period between the two groups was also significant difference. The average interval from randomization to delivery in the LMWH group was 4.2±2.1 weeks, and in the SC group was 2.0±2.0 weeks. Through the weekly AC growth measurement, the average growth rate of the LMWH group and the sildenafil group were 0.93±0.50cm and 0.67±0.37cm, respectively.p=0.003. The GA, EFW, AC and AFI of the LMWH treatment group at delivery were significantly higher than those of the control group.
The use of LMWH in FGR pregnancy is associated with a significant increase in neonatal weight, time from randomization to delivery, and improvement in fetal placental blood flow. Compared with SC, there are fewer maternal and neonatal complications.
The final results of the study showed that the weight of newborns in the LMWH group was higher than that in the SC group (p<0.000),>
finally concluded that compared with SC, the weight of newborns using LMWH, the time from randomization to delivery, and the fetal placental blood flow index were significantly improved.
When to use low molecular weight heparin
For pregnant women with FGR confirmed during pregnancy examination, attention should be paid to choosing the appropriate treatment time and early intervention. Generally, after 28 weeks of pregnancy, medication can be started according to the specific conditions of the pregnant woman. Before treatment, you should pay attention to a comprehensive assessment of the pregnant woman's condition. The treatment can be started when the pregnant woman's vital signs are stable and there are no obvious complications. The pregnant women with obvious complications should be treated first, and the pregnant woman should be in good physical condition before starting the medication. ; At the same time, the condition of the fetus should be monitored before treatment to ensure that the life of the fetus is stable, and the changes of the pregnant woman and the fetus should be closely observed at any time during the treatment.
is generally believed to receive treatment at 28-32 weeks of gestation, and the effect is relatively better. At this stage, because the fetus is generally not fully developed and mature, the growth condition is often improved after medication; after 32 weeks of gestation, the development of the fetus The maturity is relatively high, and the effect of drug treatment is often relatively poor [5]. Xiang Luojun, Xiao Yanling and others also found that low-molecular-weight heparin can effectively promote fetal growth, improve placental blood flow, and treat fetal growth restriction safely and effectively, and the earlier the treatment before 32 weeks, the better [6].
The advantages and disadvantages of using low molecular weight heparin
Fetal growth restriction is related to placenta local infarction and the patient's blood hypercoagulability. Therefore, improving placental blood perfusion and maternal blood hypercoagulability is the key to improving the therapeutic effect of fetal growth restriction. Low-molecular-weight heparin is isolated from ordinary heparin . It has the functions of reducing blood viscosity, improving blood hypercoagulability, and reducing vascular resistance. It can effectively improve placental blood supply to promote fetal growth and development.
LMWH has small side effects, does not prolong the clotting time, rarely causes coagulation abnormalities, thrombocytopenia and osteoporosis, etc., and does not pass the placental barrier . It is drug safe and has no teratogenic effect on the fetus. Foreign studies have also found that low molecular weight heparin also has a good clinical effect in improving pregnancy outcomes such as abnormal placenta and recurrent miscarriage [6]. Although low-molecular-weight heparin is superior to unfractionated heparin, its induced thrombocytopenia may still occur, bleeding adverse reactions are not uncommon, and intravenous medication is inconvenient. In order to overcome adverse reactions and make administration more convenient, in recent years, many scholars have begun to study other administration routes of low molecular weight heparin, such as oral preparations, aerosol inhalation preparations, rectal suppositories, nasal drops, etc., among which oral preparations are the main ones , Satisfactory results have been obtained in a number of experiments, and an intestinal absorption enhancer has been developed to increase the absorption and utilization of low molecular weight heparin, but all experiments are animal experiments and further research is needed. I believe that with the joint efforts of relevant scholars and experts, low molecular weight heparin will play a greater and more role [7].
In summary:
Low molecular weight heparin is more effective in treating fetal growth restriction, which is beneficial to improve the placental microcirculation, promote the normal growth and development of the fetus, and reduce the adverse perinatal outcome, and the appropriate one should be selected. The timing of treatment is early, and it is generally believed that treatment is performed at 28-32 weeks of gestation, and the effect is relatively better. It is worthy of further clinical research and promotion.
References:
1. Miao Zhijing, Huai Yingying, etc., Research advances in fetal growth restriction prediction methods, Advances in Modern Obstetrics and Gynecology, Volume 24, Issue 4, April 2015.
2. Li Haijing, Chen Yuanhong, et al., Analysis of the effect of low molecular weight heparin therapy on fetal growth restriction and perinatal outcome, Beifang Pharmacy, Volume 16, Issue 12, 2019.
3. Zhang Qingzhen, Ma Chunyi, etc., factors related to fetal growth restriction And Prevention, Journal of Clinical and Experimental Medicine, July 2010, Volume 9, Issue 14.
4. Rasheedy R, El Bishry G, Tarek R, Maternal low molecular weight heparin versus sildenafil citrate for fetal growth restriction: a randomized, parallel groups, open-label clinical trial.[J] .J Perinatol, 2020, 40: 715-723.
5. Zhou Linglin. Observation on the timing and curative effect of fetal intrauterine growth restriction[J]. Everyone's Health Edition), 2014(11):479-479,480. DOI:10.3969/j.issn.1009-6019.2014.11.628.
6. Xiang Luojun, Xiao Yanling, Zhou Wenyong, etc. Low molecular weight heparin is used to treat different gestational weeks Research on Fetal Growth Restriction[J]. Medical Theory and Practice,2016,29(6):783-784,785.
7. Pei Wen.Clinical application of low molecular weight heparin[J].Desk Reference,2009,No.7 Volume, Issue 4.
The author of this article: Qi Lei,Weiyuan County People's Hospital, Sichuan Province, general clinical pharmacist, pharmacist.
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