Method for predicting true over-mature pregnancy

FIELD: medicine, obstetrics.

SUBSTANCE: in pregnant women at pregnancy terms being after 39 wk in average portion of morning urine one should detect due to a solid-phase immunoenzymatic assay the concentration of pregnancy-associated protein-A (PAPP-A). At the level of PAPP-A being 768.2 ng/ml and more it is possible to conclude upon physiological mature pregnancy. The innovation is noninvasive and enables to increase accuracy in predicting true over-mature pregnancy.

EFFECT: higher efficiency and accuracy of diagnostics.

2 ex, 1 tbl

 

The invention relates to medicine, in particular to obstetrics.

Pregnancy complicated true perenashivanie, is still a serious problem in modern obstetrics. The frequency of advanced pregnancy ranges from 3.5 to 16%, averaging in the population of 9.9%, and has no tendency to decrease (Summary A.N., Ihnatko IV, Timokhina E.V. Comprehensive assessment of arterial and venous blood flow of the fetus and the choice of obstetric tactics during advanced pregnancy. Questions of gynecology, obstetrics and Perinatology,2003, Vol.2, No. 1, page 11-18. Rand L., Robinson K., Economy K.E. et al. Post-term induction of labor revisited. Obstet Gynecol 2000; 96 (I 5Pt): 779-783).

The urgency of the problem of a late pregnancy due to the presence of a variety of complications, the frequency of which is much higher than with timely delivery. So, at 2.3% of women delayed childbirth is accompanied by the development of discoordination generic activities in 24.4% of the observations noted primary and 10% of secondary weakness of the labour forces (Chernukha E.A. Overdue pregnancy. M.: Medicine, 1982). The frequency of oxytocin labor activation during late pregnancy increased 17 times, the total duration of childbirth increases 1.6 times and 2 times the frequency of secondary weakness of labor activity (Alexander J.M., D. Mclntire, Forty weeks and beyond: preg-nancy outcomes by week of gestation. Obstet Gynecol 2000; 96(2): 291-294.). The frequency of the shelter the currents in childbirth and the early postpartum period in late pregnancy is almost 2 times higher than timely delivery, and maternal morbidity, due to ancestral injuries, approaching 25% (Chernukha E.A. Overdue pregnancy. M.: Medicine, 1982; 250).

During advanced pregnancy increases perinatal morbidity and mortality. So, mestorozhdenii increases 6 times (Hilder L., Costeloe K., Thilaganaman Century Prolonged pregnancy: evaluating gestation - specific risks of fetal and infant mortalite. Br.J.Obstet Gynaecol 1998; 105 (2): 169-173.). 2 times increases early neonatal and postnatal mortality, diseases of newborn babies grow up to 290% (Mahjoub, S., Ben Hmid R., Dakhli R., et al. Prolonged pregnancy: apropos of a series of 102 cases. Tunis Med 2000;78 (2):125-131). The syndrome of delayed fetal growth during late pregnancy occurs in 1.7 times more likely than full-term pregnancy. Increasing incidence of chronic and acute hypoxia, aspiration syndrome meconium plug waters, in which the mortality reaches 14.5-60%, perinatal CNS damage - 60-80% of all diseases of the nervous system in children (arias F. Pregnancy and delivery high risk: TRANS. from English. - M.: Medicine, 1989, 309-321). Increased frequency odoratissima operations (Bolshakova E.E. Prediction of perinatal outcomes and obstetric tactics when postmaturity. Abstract. Diss.... Kida. the honey. Sciences. M 1996; 3-4).

A high degree of maternal and perinatal morbidity, mortality, and a variety of the complications among other things, is connected with the imperfection of the diagnosis of true perenashivanie pregnancy. (Chernukha E.A. Overdue pregnancy. M.: Medicine, 1982; 250. Arias F. Pregnancy and delivery high risk: TRANS. from English. - M.: Medicine, 1989, 309-321).

Thus, timely and objective diagnosis of the true perenashivanie pregnancy is very important and will lead to a decrease in the frequency of adverse outcomes for mother and fetus during pregnancy and childbirth.

A known method for the diagnosis of true perenashivanie pregnancy using ultrasound (ultrasound) of the amount of amniotic fluid to detect signs of low by determining the index of the amount of amniotic fluid (AFI) (Phelan JP, Ahn O., Smith C.V.et al. Amniotic fluid index measurements during pregnanse. J. Reprod. Med.,1987, 32,601). When the value of the AFI less than 5-6 cm is the diagnosis of advanced pregnancy, it is considered as a risk factor and is used as indications for labor activation (O'reilly - Green S.R., Divon M.Y. Predective value of amniotic fluid index for oligohydramnios in patients with prolonged pregnancies. J Matern Fetal Med 1996; 5(4): 218-226).

The disadvantage of this method is the subjectivity of the visual evaluation of the amount of amniotic fluid ultrasound, AFI equal to 5 cm or less, has a positive predictive value only in 50% of cases (O'reilly - Green S.R., Divon M.Y. Predective value of amniotic fluid index for oligohydramnios in patients with prolonged pregnancies. J Matern Fetl Med 1996; 5(4): 218-226), water scarcity is not a specific sign of perenashivanie and occurs as early and unwanted pregnancy, regardless of pregnancy in inflammatory lesions of the fetal membranes, chronic endometritis, endocrine abnormalities, preeclampsia (Milovanov A.P. Pathology system mother-placenta-fetus: guidelines for physicians. Medicine, 1999; 326-338).

A known method for the diagnosis of true perenashivanie pregnancy by functional assessment of the fetal condition using antenatal machine (CTG) using actresslove test (nst), allowing detection of a decrease in the heart rate variability of the fetus and the emergence of decelerate, and oxytocin contractile test (OCT), which measures the degree of biological readiness of the uterus for childbirth (arias F. Pregnancy and delivery high risk: TRANS. from English. - M.: Medicine, 1989, 316-317).

The disadvantage of this method is ineffective PCT when postmaturity (PB) (Li T., G.G. Rhoads, Demissie, K. et al. The efficacy of non-stress test in preventing fetal death in post-term pregnancy. Paediatr Perinat Epidemiol 2001; 15(3): 265-270), the lack of specificity CTG criteria for delayed delivery (Cibils L.A., Votta R. Clinical significance of fetal heart rate patterns during labor. IX: Prolonged pregnancy.J Perinatal Med 1993; 23(2): 107-116), a high risk of fetal death before the birth and at the time these women with the IB, in which a few on the up, it's with the PCT and OCT confirmed the satisfactory condition of the fetus (CIT. by arias F. Pregnancy and delivery high risk: TRANS. from English. - M.: Medicine, 1989, 317).

Closest to the claimed is true diagnosis of perenashivanie pregnancy by determining the level of placental lactogenic (PL) in the serum of pregnant, when to reduce its level reveal the degree of dysfunction of the placenta, on the basis of what is judged on the length of perenashivanie pregnancy in each case (Serov V.N., The summary A.I., Markin, S.A. Manual of practical obstetrics: M: OOO Medical information Agency, 1997. - P. 203).

The disadvantage of this method is its invasiveness and lack of specificity for advanced pregnancy decrease the level of DPS, because the lower level DPS is often observed with the threat of spontaneous termination of pregnancy, chronic placental insufficiency, fetal malnutrition, preeclampsia, regardless of the duration of pregnancy (Anastasia VG Morphofunctional disorders Feto-placental complex with placental insufficiency. - Novosibirsk, 1997. P.98-102).

The objective of the invention is to improve the accuracy of diagnosis and prognosis true perenashivanie pregnancy by determination of enzyme-linked immunosorbent method concentration associated with pregnancy protein-A (Papp-a) in the urine of pregnant W is nmin.

This object is achieved in that in pregnant women in midstream morning urine enzyme-linked immunosorbent method determines the concentration associated with pregnancy protein - A (Papp-a) after 39 weeks of pregnancy and when it is over 768,2 ng/ml judged true advanced pregnancy.

The novelty of the method:

- pregnant women are examined in the urine concentration of Papp-a in pregnancy after 39 weeks;

for Papp-a more 768,2 ng/ml judged true advanced pregnancy.

This indicator was chosen due to the fact that associated with pregnancy protein-A (pregnancy-associated plasma protein A) Papp-a, representative collection macroglobulin, has a unique structure and properties. During pregnancy the main producer of Papp-a is trophoblast, which explains the strong correlation between its concentration and the mass of the placenta. Papp-a determines in the later stages of pregnancy, the possibility of delivery, as deficiency, spontaneous miscarriages and premature birth (Coddington S., et al. Papp-a does not improve the predictability of pregnancy success or failure over human chronic gonadotrophin levels in early normal and abnormal pregnancy. Fertil steril. - 1989. - Vol.52. - P.854-857). When increasing the concentration of Papp-a in plasma and urine may reverse the phenomenon of inhibition delivery Use as a substrate for determining the concentration of biochemistry And urine has significant advantages due to the non-invasive approach. This allows you without any risk to pregnant repeatedly perform the refinement results of the analysis, greatly increasing the accuracy of diagnosis of advanced pregnancy.

However, in the obstetric literature works on the prediction and diagnosis of true perenashivanie pregnancy by examining the concentration of Papp-a in the urine we have not met.

The claimed method applied to dynamic continuous bezvyhodnom examination 616 pregnant. After retrospective analysis of the course they have pregnancy and childbirth, were allocated to 2 groups: the 1st group consisted of 46 pregnant women with physiological full-term pregnancy, childbirth which was uneventful with gestational age 39-41 weeks., the 2nd group consisted of 16 pregnant with true perenashivanie, childbirth which operates at a gestational age greater than 42 weeks. The diagnosis of true perenashivanie was confirmed before delivery when calculating the duration of pregnancy, higher than normal for 10-14 days (i.e. 290-294 days)after birth - with-finding signs of perezrevaniya in the fetus and histological examination of the placentae.

The results of the study are presented in table 1.

Table 1

The concentration of Papp-a (ng/ml) in urine and 95% confidence intervals values (95% CI) at physiological to Osenniy pregnancy and the true perenashivanie.
IndicatorsThe group surveyed
Full term pregnancyOverdue pregnancy
n4616
X+m184,7±11,0933,0±43,0*
95% CIowed 161.1-of 208.3768,2-1124,7
Note. * - differences statistically significant compared with the level at term pregnancy.

The method consists in the following: a pregnant woman at term pregnancy after 39 weeks take the middle portion of morning urine and enzyme-linked immunosorbent method using the test system of own production (Zorin N.A. et al., Plasma proteins and serum of blood donors. Clinical and laboratory diagnosis. 1992, No. 9-10, C-15) define it as the concentration of PAPP-A. the Obtained results were evaluated as follows: the concentration of Papp-a less than 300 ng/ml corresponds to physiological full-term pregnancy, the 768,2 ng/ml corresponds to a true advanced pregnancy.

Example 1.

Pregnant So, 23 years old, no history of pregnancy and childbirth 759/576. This fourth pregnancy: the first one ended term births without complications, the second and third copper is Ty abortion without complications. First day of last menstruation - 21.06.2002, about this pregnancy was observed in the antenatal clinic with 11 weeks of pregnancy, before delivery, only 10 times. During the regulated dynamic observation and examination of a pregnant detected physiological course of pregnancy. The concentration of Papp-a in the urine during pregnancy is 40 weeks (1 day before delivery) - 170 ng/ml Childbirth, according to the date of the last menstrual period and ultrasound, occurred during the period of pregnancy is 40 weeks (24.03.2003 g) the Duration of labour 6 h 25 min, without complications. Born Mature boy weighing 3200 g, a growth of 5 cm, 8/9 points on the Apgar scale, with no signs of perezrevaniya. Discharged from the hospital on the 5th day with the child in a satisfactory condition home.

Example 2.

Pregnant D., 26 years old, no history of pregnancy and childbirth 87. This fifth pregnancy, previous ended urgent delivery without complications. About this pregnancy was observed in female consultations't regularly with 34 weeks of gestation, only 4 times. Date of first day of last menstrual period - 05.05.02, was Admitted into the hospital 27.02.03, with the diagnosis of pregnancy of 42 weeks, suspected the true overcarrying, chronic fetoplacental insufficiency, chronic hypoxia. The examination found no PR the characters anatomical and biological readiness of the pregnant woman's body for childbirth, on CTG is an indicator of fetal status is 1.9, ultrasound signs of aging of the placenta, placental insufficiency, low. The concentration of Papp-a in the urine - 1200 ng/ml In connection with diagnosis of true perenashivanie pregnancy, lack of conditions for conservative genera and tolerance of the fetus to a conservative genera 28.02.03, made a delivery by caesarean section, during which the detected intense meconium plug staining of amniotic fluid and oligohydramnios. Retrieved boy, weighing 3850,0, height - 50 cm, with estimation on Apgar scale - 3/6 points, with signs of perezrevaniya (the skin and the umbilical cord painted meconium, maceration of the skin, no Carovigno lubrication, long nails, weak development of subcutaneous fat). Histological examination of the placenta is found signs of "aging" of the placenta and placental insufficiency (calcifications, fibrous degeneration of the villi, microinfarct). On the 3rd day after birth the child was transferred to the neonatal care unit, children's hospital, where he was discharged on the 17th day after birth. The postoperative period is correct, the woman was discharged on the 10th day in a satisfactory condition.

Thus, the proposed method for the diagnosis of true advanced pregnancy pregnant by research in the middle of porci the morning urine concentrations of Papp-a using enzyme-linked immunosorbent method is a noninvasive method, an objective criterion for evaluation of pregnancy, prognostic and diagnostically significant indicator when the true postmaturity. The accuracy of the diagnosis was confirmed clinically and sensitivity - at physiological full-term pregnancy, 97%, with advanced pregnancy 100%, and specificity 98,0%.

The way to diagnose the true perenashivanie pregnancy by examining the biological fluid, wherein in pregnant women at term pregnancy after 39 weeks determine enzyme-linked immunosorbent method in midstream morning urine concentration associated with pregnancy protein - A (Papp-a) and at the level 768,2 ng/ml or more is judged true advanced pregnancy, when levels less than 300 ng/ml judged physiological full-term pregnancy.



 

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