[Show abstract][Hide abstract] ABSTRACT: Recurrent spontaneous abortion (RSA) may have immunological etiology. The aim of this study was to assess the efficacy of a high dose intravenous immunoglobulin (HIVIg) therapy, in which 20 g of intact type immunoglobulin was infused daily for 5 days during early gestation, for women who had a history of four or more consecutive spontaneous abortions of unexplained etiology. A total of 60 pregnant RSA women underwent HIVIg therapy, and the pregnancy outcome was assessed. The live birth rate was 73.3% (44/60). Fifteen pregnancies ended in spontaneous abortion, and one ended in intrauterine fetal death. In 11 of the 15 spontaneous abortions, fetuses had abnormal chromosome karyotype. When the 11 pregnancies with abnormal chromosome karyotype were excluded, the live birth rate was as high as 89.8% (44/49). The HIVIg therapy may be effective for severe cases of unexplained RSA.
ISRN obstetrics and gynecology 09/2012; 2012:512732. DOI:10.5402/2012/512732
[Show abstract][Hide abstract] ABSTRACT: We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.
Journal of Obstetrics and Gynaecology Research 02/2011; 37(2):151-5. DOI:10.1111/j.1447-0756.2010.01324.x · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We encountered a woman who had a history of repeated fetal losses and positive tests for lupus anticoagulant, phosphatidylserine-dependent
antiprothrombin (aPS/PT) IgG, IgM and kininogen-dependent antiphosphatidylethanolamine (aPE) IgG, IgM. Her previous pregnancy
had ended in intrauterine fetal death at 24weeks of gestation despite a therapy of low-dose aspirin, prednisolone and danaparoid.
During the present pregnancy, she was treated with repeated intravenous infusions of immunoglobulin (IVIg) together with low-dose
aspirin, prednisolone and heparin. When thrombocytopenia developed, she delivered a female baby weighing 2,152g at 34weeks
of gestation by cesarean section. Titers of aPS/PT IgM and aPE IgM were reduced or maintained at low levels by repeated IVIg
therapies. The IVIg therapy might be effective for aspirin-heparinoid-resistant antiphospholipid syndrome.
Reproductive Medicine and Biology 12/2010; 9(4):217-221. DOI:10.1007/s12522-010-0056-3
[Show abstract][Hide abstract] ABSTRACT: A 35-year-old Japanese nulliparous woman exhibited rapid weight gain (6 kg/7 days), reduced antithrombin activity and platelet count at 37 weeks of gestation without hypertension or proteinuria, and underwent cesarean section. Postnatally, pulmonary edema developed for 7 days, with transient hypertension and proteinuria, and bodyweight loss (14.6 kg) by 14 days postpartum. Platelet count and antithrombin activity normalized promptly postpartum. Despite a life-threatening clinical condition due to enhanced vascular permeability, neither hypertension nor proteinuria appeared antenatally. Determining antithrombin activity and platelet count may be useful for distinguishing between women with pathological edema and physiological edema.
Journal of Obstetrics and Gynaecology Research 08/2010; 36(4):861-5. DOI:10.1111/j.1447-0756.2010.01191.x · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective study was performed to characterize the laboratory features and water metabolism of women with pregnancy-induced antithrombin deficiency (PIATD).
Among 1493 women who gave birth to a singleton infant at our institution, 114 women who developed PIATD and/or pregnancy-induced hypertension (PIH) were reviewed with respect to perinatal changes in laboratory variables (hematocrit value, fibrinogen, fibrinogen degradation product, D-dimer, uric acid, aspartate aminotransferase, lactate dehydrogenase) and body weight. PIATD was defined as a gradual decline in antithrombin (AT) activity to <or=65% of normal activity levels. One hundred and fourteen women with neither PIATD nor PIH and matched for the cesarean delivery rate were selected as a control group.
Of the 81 women who developed PIH, 19 (23.4%) also developed PIATD. Thirty-three women developed PIATD in the absence of PIH. Coagulation-fibrinolysis was significantly more enhanced and the postpartum reduction in the hematocrit value was significantly larger in women with PIATD, irrespective of the presence or absence of hypertension, than in women without PIATD. The postpartum decrease in body weight was significantly smaller in women with PIATD, irrespective of the presence or absence of hypertension.
A decrease in AT activity may occur in the absence of hypertension. Even in the absence of hypertension, a decreased plasma volume and enhanced coagulation-fibrinolysis seem to characterize women with PIATD. The monitoring of AT activity may help in distinguishing pregnant women with these insidious risks.
Journal of Perinatal Medicine 05/2010; 38(4):379-85. DOI:10.1515/JPM.2010.049 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics and intravenous immunoglobulin may improve outcome of pregnant women suffering from flu-like symptoms, shock and strong uterine contractions suggestive of placental abruption.
The Journal of infection 03/2010; 60(6):417-24. DOI:10.1016/j.jinf.2010.03.011 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy.
By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8).
Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 +/- 21.4% versus 71.0 +/- 17.6%).
Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity.
American Journal Of Reproductive Immunology 11/2009; 62(5):301-7. DOI:10.1111/j.1600-0897.2009.00739.x · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytogenetic amniocentesis (CA) has been performed as a reliable prenatal diagnostic method for decades. The aims of the present study were to reveal the frequency of fetal chromosome abnormalities according to medical indications of CA, and to assess the risks of specific abnormal ultrasound findings. Data on chromosome karyotypes of fetuses from 5043 Japanese mothers were collected. Group I comprised 4626 fetuses whose mothers underwent CA due to a variety of parental reasons. Group II comprised 417 fetuses whose mothers underwent CA due to fetal abnormality, abnormality of amniotic fluid volume and fetal growth restriction. The frequency of chromosome abnormalities in Group II (17.7%) was significantly higher than in Group I (1.8%). The frequencies of chromosome abnormalities in Group II singleton fetuses with fetal abnormality, polyhydramnios and fetal growth restriction were 21.5, 22.9 and 19.6%, respectively. By multivariate analyses, we found that cystic hygroma (odds ratio 5.6, 95% CI 2.7-11.6), abnormal extremity (5.0, 1.7-14.4) and cardiovascular abnormality (3.3, 1.1-10.1) were significant variants associated with fetal chromosomal abnormalities. Information revealed in the present study constitutes a beneficial reference for genetic counseling.
[Show abstract][Hide abstract] ABSTRACT: Administration of high-dose intact human immunoglobulin (IH-Ig) has been applied to treat a variety of inflammatory and autoimmune diseases, and is expected to have beneficial effects on human fecundity. In the present study, we investigated whether Ig had anti-resorption effects using polyinosinic-polycytidylic acid sodium salt [poly (I:C)]-induced enhancement of fetal resorption in the mating of CBA/J x DBA/2J resorption-prone mouse model. Furthermore, we investigated the mechanism of the effect by examining the mRNA expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-10, IL-4 and TGF-beta(1) in spleens and placentas from the resorption-prone model treated with IH-Ig, by reverse transcription (RT)-polymerase chain reaction (PCR). Administration of high-dose IH-Ig significantly reduced the fetal resorption rate from 55% to 10%. This anti-resorption effect, however, was not detected in mice administered with Fab fragments of human Ig. We then performed adoptive transfer experiments to examine whether cellular components could transfer the effect. A remarkable anti-resorption effect was seen in poly (I:C)-injected pregnant recipients transferred with spleen cells from IH-Ig-treated donor mice. The RT-PCR study showed that IH-Ig reduced the expression of IFN-gamma and TNF-alpha mRNA in placentas of poly (I:C)-injected pregnant mice. The present findings demonstrate that intact Ig, particularly its Fc portion, possesses anti-resorption activity. The effect might be attributed to the suppressed production of pro-inflammatory cytokines at the maternofetal interface.
Molecular Human Reproduction 12/2007; 13(11):807-14. DOI:10.1093/molehr/gam061 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There has been no study concerning association between topological factors of placental vascularization and neonatal growth in humans. The aim of study was to assess whether any network index of placental surface arteries was associated with neonatal birth weight.
Twenty-six placentas were randomly selected between 34 and 41 weeks of gestational ages. Placental weights ranged 385 to 770 g; and neonatal weights ranged 1960 to 3680 g. After visualization of placental surface arteries by a milk injection method, network indices including the number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were determined. These network indices and placental weights were compared with neonatal birth weights.
The number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were found to be as follows (Mean +/- SD); 84.7 +/- 29.3, 0.0262 +/- 0.0088, 15.8 +/- 2.77, 7.83 +/- 1.13, 0.0263 +/- 0.0091, respectively. We found that neonatal birth weights correlated with the number of nodes of placental surface arteries (correlation coefficient R = 0.40) and placental weights (R = 0.52) both. However, the number of nodes of placental surface arteries was not associated with the placental weights or the gestational age.
We for the first time found that a topological factor, i.e., the number of nodes of placental surface arteries correlated with neonatal growth. There was no correlation between numbers of nodes and placental weights. This suggests that the number of nodes affects fetal growth independent of placental weights. A topological factor of placental vascularization might significantly affect fetal growth in utero and determine risks of vascular diseases in their future lives.
[Hokkaido igaku zasshi] The Hokkaido journal of medical science 10/2006; 81(5):365-70.
[Show abstract][Hide abstract] ABSTRACT: The aim of this cohort study was to assess natural killer (NK) cell and natural killer T (NKT) cell populations and cytokine expressions of helper T (Th) and cytotoxic T (Tc) cells in the decidua of sporadic miscarriage (MS) and induced abortion (IA).
The deciduae were obtained from consecutive 40 women whose pregnancies ended in the first trimester MS, and the fetal chromosome karyotypes were analyzed. The cell populations were measured by flow cytometry.
No significant differences in NK cell or NKT cell percentages were found among MS with normal chromosome karyotype (MSNK, n = 14), MS with abnormal karyotype (MSAK, n = 26) and IA (n = 14). Interferon (IFN)-gamma(+) cell percentage and interleukin (IL)-4(+)/tumor necrosis factor (TNF)-alpha(+) ratio of Th cells in MS groups were increased, while IL-4(+) cell percentage, IL-4(+)/IFN-gamma(+) and IL-4(+)/TNF-alpha(+) ratios of Tc cells in MS groups were decreased as compared with those in IA. No significant difference in these parameters between MSNK and MSAK was found.
These results suggested that Tc1 predominance existed in the decidua of MS. Th1 predominance was not found in MSNK.
American journal of reproductive immunology (New York, N.Y.: 1989) 10/2006; 56(3):193-200. DOI:10.1111/j.1600-0897.2006.00417.x · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether the C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene and the Leiden mutation of coagulation factor V (FV) are associated with recurrent spontaneous abortion (RSA) of unexplained etiology in Japanese participants, the genotypes of the two polymorphisms were determined and compared between cases of unexplained RSA and normal pregnant controls. Eighty-three Japanese participants, consisting of 45 women with explained RSA and 38 women with unexplained RSA, and 174 controls were recruited in the study. The frequencies of the T677 allele/TT genotype were not significantly different among women with explained RSA (35.6%/13.3%), women with unexplained RSA (34.2%/7.9%), primigravid controls (35.1%/11.7%), and multigravid controls (39.7%/16.5%). In the cases of unexplained RSA, the frequencies of the T677 allele and TT genotype tended to increase according to the number of previous spontaneous abortions, but the increase was without statistical significance: the frequencies of the T677 allele and TT genotype in women with two abortions were 18.2% and 0%, whereas in women with three abortions the frequencies were 38.0% and 9.5%, and in women with four or more abortions the frequencies were 50.0% and 16.7%, respectively. In addition, no Leiden mutation of FV was detected in the women with RSA or the controls. Neither T677 of the MTHFR nor the Leiden mutation of FV was associated with unexplained RSA in the Japanese population.
Seminars in Thrombosis and Hemostasis 07/2005; 31(3):266-71. DOI:10.1055/s-2005-872430 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this cohort study was to investigate immunophenotypic characteristics of natural killer (NK) cells by assessing specific molecules expressed in the decidua of sporadic miscarriages and induced abortions. The deciduae were obtained from 29 consecutively seen women whose pregnancies ended in first trimester miscarriages (MS), and the fetal chromosome karyotype of these MS was analysed. Additionally, 13 deciduae were obtained from induced abortion (IA) with informed consent. The expression of perforin, CD94, CD161, CD158a, CD158b, CD244 on CD3-CD56+NK cells, and perforin on CD3+CD8+ T cells was analysed by flow cytometry. The CD158a (mean+/-SD, 26.2+/-14.7%) and CD94 (50.2+/-25.7%) expressions in MS with normal chromosome karyotype (MSNK; n=11) were significantly decreased as compared with those (41.5+/-19.5%, 71.4+/-20.4%) in MS with abnormal karyotype (MSAK; n=18) and those (44.3+/-21.9%, 80.8+/-17.5%) in IA (n=13). Conversely, the perforin expression on CD3-CD8-CD56+NK cells (76.3+/-11.0%) and CD3+CD8+T cells (30.6+/-9.2%) in MSNK was significantly increased as compared with those (66.8+/-16.6%, 23.6+/-8.7%) in MSAK and those (62.9+/-11.6%, 19.7+/-8.1%) in IA. A positive correlation between CD94 and CD158a expressions on NK cells, negative correlations between CD94 on NK cells and perforin on NK cells/T cells, and between CD158a on NK cells and perforin on T cells were found in the decidua. A divergence of NK cell repertoire in the decidua might be related to aetiology of sporadic MSNK.
Molecular Human Reproduction 07/2005; 11(6):451-7. DOI:10.1093/molehr/gah181 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.
Molecular Human Reproduction 11/2004; 10(10):729-33. DOI:10.1093/molehr/gah096 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess pregnancy loss patterns in women with repeated miscarriage (RM), according to fetal chromosome karyotypes and aetiologies of RM.
In this cohort study, 168 fetal chromosome karyotypes of miscarriages were investigated. The pregnancy loss patterns were compared between 75 miscarriages from RM women who had a history of two or more consecutive miscarriages and 93 miscarriages from control women whose previous pregnancies ended in live births without a history of RM. By serial ultrasonography, embryo loss (EL) was defined as miscarriage before fetal heat movement was identified and fetal loss (FL) as miscarriage after fetal heat movement was identified. The EL rate was calculated as EL/(EL+FL).
The EL rate (66.7%) in miscarriages with normal karyotypes among RM women (n=42) was higher (P<0.05) than that (45.7%) in controls (n=46), while the EL rate (30.3%) in miscarriages with abnormal karyotypes among RM women (n=33) did not differ from that (25.5%) in the controls (n=47). The EL rate (71.4%) in miscarriages with normal karyotypes among unexplained RM women (n=21) was much higher (P<0.05) than that in the controls.
By evaluating fetal karyotypes, we demonstrated for the first time that EL was predominant in miscarriages with normal karyotype among RM women.
Human Reproduction 11/2004; 19(11):2644-7. DOI:10.1093/humrep/deh451 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enhanced secretion of type-2 T-helper (Th2) cytokine is a characteristic feature in normal physiological pregnancy. A study has demonstrated defective production of interleukine-4 (IL-4) and other Th2 cytokine in women with recurrent pregnancy loss (RPL). Several studies have suggested that IL-4 variable number of tandem repeat (VNTR) gene polymorphism is probably associated with different IL-4 production.
The IL-4 VNTR genotypes were assessed in 109 Japanese women with RPL and 210 ethnically matched women experiencing at least one live birth and no spontaneous abortion.
No significant differences in IL-4 VNTR genotype frequencies were found between the RPL and the control [B1B1 genotype (reference); B1/B2 and B2/B2 genotypes, odds ratio, 0.91; 95% confidence interval, 0.58-1.45].
The present study suggests that the IL-4 VNTR allele is not a major genetic regulator in RPL.
American journal of reproductive immunology (New York, N.Y.: 1989) 09/2004; 52(2):143-6. DOI:10.1111/j.1600-0897.2004.00193.x · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess whether or not serum cytokine concentrations during early pregnancy are related to the subsequent outcomes in women with recurrent spontaneous abortion (RSA).
Serum concentrations of five cytokines--tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-4, IL-6, and IL-10--were measured by ELISA methods. Sera were collected from 73 RSA women at 6-7 weeks of gestation. Of the 73 pregnancies, 10 subsequently ended in abortion with normal fetal chromosome karyotype (AbNK), 12 ended in abortion with abnormal karyotype (AbAK), and the other 51 pregnancies ended in live birth (Lb).
The serum TNF-alpha concentration in women with AbNK (mean 0 pg/ml) was lower than that in women with subsequent AbAK (0.06 pg/ml) (p < 0.05). The TNF-alpha positive percentage among women with AbNK (0%) was also lower than that among women with AbAK (50.0%) (p < 0.05).
Decreased serum TNF-alpha concentration during early pregnancy might be associated with subsequent abortion in RSA women.
[Hokkaido igaku zasshi] The Hokkaido journal of medical science 05/2004; 79(3):237-41.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the natural killer (NK) cell and natural killer T (NKT) cell populations and cytokine expression of T-helper (Th) cells in the endometrium of women who suffered from unexplained repeated miscarriage (RM).
The percentages of NK cells, NKT cells and CD4(+) cells expressing intracellular interferon (IFN)-gamma, interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha were measured by flow cytometry in the endometrium of 20 RM women and 17 fertile control women in the mid-luteal phase of the menstrual cycle.
No significant differences in CD56(+) NK cell or CD3(+)CD4(-)CD8(-)Valpha24(+)Vbeta11(+) NKT cell percentages were found between RM and control women. However, in RM women compared with control women, the percentages of CD3(+) cells (mean 40.3 versus 56.5%), CD4(+)IFN-gamma(+) cells (28.4 versus 39.5%) and CD4(+)TNF-alpha(+) cells (32.9 versus 45.8%) were significantly lower. The Th1/Th2 cell balance in RM women did not differ from that of controls.
Immunodystrophism detected as diminution of the Th cell population rather than Th1 predominance, NK cell or NKT cell accentuation in the endometrium might underlie the pathophysiology of unexplained RM. This finding provokes an additional controversy on the Th1/Th2 balance concerning RM aetiology.
Human Reproduction 05/2004; 19(4):1018-24. DOI:10.1093/humrep/deh159 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate immunophenotypic characteristics of natural killer (NK) cells by assessing specific molecules expressed in women with recurrent spontaneous abortion (RSA) of unexplained etiology.
Peripheral blood cells were obtained from 20 RSA women and 15 fertile controls. The expression of perforin, CD94, CD161, CD158a, CD158b, and CD244 on CD3- CD56+ NK cells was analyzed by flow cytometry.
A significant decrease in CD158a expression was demonstrated in RSA women (mean +/- SD, 22.9 +/- 8.7%) as compared with that in controls (33.6 +/- 15.7%) (P < 0.05). The percentage of NK cells showing dual expression of CD94 and CD161 was relatively higher in RSA women (55.1 +/- 10.2%) than in the controls (47.1 +/- 19.0%), but without statistically significant (P = 0.096). The expression of perforin, CD158b, or CD244 in RSA women did not differ from that in the controls.
A divergence of the specific NK cell repertoire might be related to the etiology of RSA.
American journal of reproductive immunology (New York, N.Y.: 1989) 03/2004; 51(3):241-7. DOI:10.1111/j.1600-0897.2004.00139.x · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intrauterine fetal growth restriction is a multifactorial disorder, and its aetiology includes both environmental and genetic components. We aimed to investigate whether maternal genetic polymorphisms of metabolic enzymes affects fetal growth and pregnancy duration. Genomic DNA was obtained from 134 women who experienced singleton deliveries beyond 24 weeks of gestation. Maternal age, birth weight, gestational age at birth and frequencies of fetal growth restriction, prematurity and pregnancy-induced hypertension were compared among genotypic subgroups of cytochrome p450 (CYP) and glutathione S-transferase (GST) genes. The polymorphisms of CYP1A1 (MspI), CYP17 (MspAI) and GSTP1 (BsmAI) genotypes, and the presence or absence of GSTM1 and GSTT1 genes were analysed by PCR-based methods. The frequency of fetal growth restriction (<10th percentile/<-1.5 SD; 22.7%/11.4%) in 44 women who were homozygous for the A1 allele (A1A1) of CYP17 was significantly higher than that (7.8%/2.2%) in 90 women who carried the A2 allele (A1A2/A2A2) of CYP17 (P < 0.05), with an odds ratio =3.41 (95% confidence interval = 1.18-9.84). The gestational age at birth (mean +/- SD, 37.5 +/- 3.1 weeks) in 67 women with GSTM1 null genotype was significantly lower than that (38.5 +/- 2.4 weeks) in 67 women who carried GSTM1 (P < 0.05). The polymorphism of CYP17 that encodes the cytochrome p450c17alpha enzyme might be associated with the pathophysiology underlying fetal growth restriction.
Molecular Human Reproduction 02/2004; 10(1):49-53. · 3.48 Impact Factor