Twentieth Week Of Gestation Research Articles

Anatomy and Physiology of the Breast during Pregnancy and Lactation.

The mature breast is located within the anterior thoracic wall, lying atop the pectoralis majormuscle. Pubertal changes lead to incomplete development of the breast , a process which is only completed during pregnancy . The incomplete breast consists mostly of adipose tissue but also lactiferous units called lobes. These eventually drain into the lactiferous ducts and then into the lactiferous sinus and then to the nipple-areolar complex. During pregnancy , the breast undergoes both anatomic and physiologic changes to prepare for lactation. During the first trimester, the ductal system expands and branches out into the adipose tissue in response to the increase of estrogen. Elevated levels of estrogen also cause a decrease in adipose tissue and ductal proliferation and elongation. Estrogen also stimulates the pituitary gland which leads to elevated levels of prolactin. By the twentieth week of gestation, mammary glands are sufficiently developed to produce components of milk due to prolactin stimulation. Milk production is inhibited by high estrogen and progesterone levels and colostrum is produced during this time. In the third trimester and then rapidly after birth, these levels decrease, allowing for milk production and eventual let-down to allow for breastfeeding. Most pregnancies cause the areola to darken, the breast to increase in size, and the Montgomery glands to become more prominent. Post-lactational involution occurs at the cessation of milk production caused by a decline in prolactin.

The Expression of T-Helper Associated Transcription Factors and Cytokine Genes in Pre-Eclampsia.

Pre-eclampsia (PE) is known as a main factor contributing to fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth week of gestation. The balance of T helper subsets is essential to sustain a normal pregnancy and preventing fetomaternal complications. To investigate differences in the levels of transcription factors and cytokine gene expression of Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15 PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy. Using Quantitative real-time PCR (Q-PCR), the expression of T-BET, GATA-3, ROR-ɣt, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4, IL-31, IL-17, IL-23, TGF-β1, TGF-β2, TGF-β3, and IL-35 in the placenta were compared at mRNA levels between groups. FOXP3 and GATA-3 were significantly down-regulated, while T-BET was up-regulated in PE deciduae compared to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides, most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-ɣ/IL-35, IL-6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy controls. Our results shed more light on the contribution of Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy. Moreover, regulatory T cells and IL-35 seem to play a notable role in pre-eclampsia.

Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss.

Idiopathic recurrent pregnancy loss (IRPL) is defined by three or more consecutive miscarriages occurring before the twentieth week of gestation as a result of unidentified etiological factors. The results of previous studies have indicated that prothrombotic factors play a pathogenic role in early and late pregnancy. This study aimed to identify inherited prothrombotic and hypofibrinolytic risk factors in Mexican-Mestizo patients with IRPL. Fifty-six women with IRPL and 50 control women with at least two full-term pregnancies and no history of RPL were included in this case-control study. Four prothrombotic (F5 G1691A, F2 G20210A, MTHFR C677T-A1298C) and one hypofibrinolytic (PAI1 4G/5G) restricted fragment length polymorphisms were subjected to molecular analysis. In the case of hypofibrinolytic ACE Ins/Del (I/D), identification was performed by direct PCR. The independent risk correlated with the presence of polymorphisms in IRPL patients was estimated using odds ratio (OR) with a 95% confidence interval (CI). MTHFR 677TT was the most frequent prothrombotic factor in the IRPL group (23%), followed by the compound-heterozygous C677T-A1298C (16%) and heterozygous F2 20210GA (3.6%). The heterozygous ACE I/D (62%) was the main hypofibrinolytic risk factor of IRPL, followed by the homozygote PAI1 4G/4G (18%). The ACE I/D polymorphism was the only significantly different factor among the cases and controls. The dominant genetic model D/D+I/D vs I/I showed an OR (95%CI) of 2.89 (1.22-6.89) and P = 0.019 in Mexican-Mestizo women. The results of this study support an association between the ACE I/D polymorphism and IRPL risk in a Mexican population.

Quando introduzir o tratamento farmacológico na pré-eclâmpsia

Sabe-se que cerca de 10% das gestações cursam com hipertensão arterial, o que representa a primeira causa de mortalidade materna no Brasil. A pré-eclâmpsia é condição sistêmica que se manifesta clinicamente com o aparecimento de hipertensão arterial após a 20ª semana de gestação, em mulheres previamente normotensas, associado à proteinúria. Não há consenso na literatura sobre a conduta farmacológica mais adequada e tampouco se há vantagens em usar fármacos anti-hipertensivos nos casos de pré-eclâmpsia. Sendo assim, este artigo busca reunir informações de pesquisa em bancos de dados, como Cochrane Library, Medline (por meio do Pubmed), Google acadêmico e SciELO, a fim de revisar a conduta proposta atualmente para o tratamento anti-hipertensivo de manutenção da pré-eclâmpsia. As mais usadas são aquelas que não trazem riscos ao binômio materno-fetal ou seus riscos são mínimos, como a hidralazina, nifedipina, alfa-metildopa e labetalol. Contudo, concluímos que não há conduta padrão e, sendo assim, a escolha do medicamento vai depender da experiência de cada obstetra e da rotina adotada para aquele serviço. Descritores : Pré-eclâmpsia; Anti-hipertensivos; Gravidez.

The transcription factor Forkhead Box P3 gene variants affect idiopathic recurrent pregnancy loss

IntroductionForkhead Box P3 (FOXP3) is an essential transcription factor for the induction and development of Tregs. It plays an important role in regulation and suppression of immune responses. We tested whether FOXP3 gene variants are associated with idiopathic recurrent miscarriages (IRM). MethodsWe included 200 women with at least three unexplained spontaneous abortions before twentieth week of gestation and 300 healthy parous women. The detection of genetic variants of rs2232365, and rs5902434 SNPs were carried-out by using polymerase chain reaction (PCR) with sequence-specific primers, while rs3761548 and rs2294021 SNPs were genotyped by PCR followed by RFLP analysis. The logistic odds ratios (ORs) of idiopathic RM risk were estimated with a 95% confidence interval (CI) after maternal age adjustment. Multifactor dimension reduction (MDR) analysis was used to evaluate the potential SNP ∼ SNP interactions. ResultsSingle marker analysis revealed an increased risk ranged from almost 3-fold–2-fold for rs2232365, rs3761548, rs5902434 and rs2294021 SNPs in IRM cases. The mutant haplotype carriers of rs2232365, rs3761548, rs5902434 and rs2294021 SNPs showed an increased risk of 2.5-fold for IRM cases. Linkage disequilibrium analysis revealed moderate LD between rs2232365, rs3761548, rs5902434 and rs2294021 SNPs. The MDR analysis revealed 6-fold increased risk for IRM cases in four factor models of rs2232365, rs3761548, rs5902434 and rs2294021 SNPs. The maximum testing accuracy, highest cross validation consistency and greater significance was observed in four SNP model. DiscussionThese results suggest that variants of FOXP3 SNPs namely; rs2232365, rs3761548, rs5902434 and rs2294021 may be associated with idiopathic RM.

Increased Miscarriage Rate in Female Farmers Working in Saffron Fields: A Possible Effect of Saffron Toxicity

Background: There is much debate about effects of medicinal plants such as saffron (Crocus sativus) on human health. Women are highly involved in farming and processing of this plant. This study is aimed at evaluating the saffron impacts on miscarriage rate of female farmers working in saffron fields. Methods: This was a prospective case-control study on pregnant female farmers during harvesting season of saffron in December 2005 to evaluate miscarriage rate among them. All pregnant women who were between the first and twentieth week of gestation and were participated in saffron harvesting and processing in previous years were studied. The subjects were divided into two age and gestational age-matched groups of cases and controls. The cases were prohibited from working in saffron fields and in return they were paid same as the average amount of their monthly income. They were trained not have any exposure to saffron and a team supervised them on their adherence during the study period. Nevertheless, they were free for working in other careers. On the other hand, the controls were allowed for working in the fields and processing saffron. Results: Forty-one subjects were included in case group and 38 subjects in control group. Median age of all subjects was 25 years. The groups were not significantly different from each other according to history of miscarriage and 2nd occupation. Four subjects experienced miscarriage that all of them belonged to control group having contact to saffron. None of cases had miscarriage. Using Fisher's exact test, it was found that miscarriage rate was significantly higher (10.6% vs. 0%, P = 0.03) among female farmers who had saffron exposure. Conclusion: Exposure to saffron may increase the risk of miscarriage. Hence, it is suggested that pregnant women avoid contact with considerable amounts of saffron especially for female farmers working in saffron fields.

The effect of HLA-DRB1 sharing between the couples with recurrent pregnancy loss on the pregnancy outcome after leukocyte therapy.

Miscarriage is a common phenomenon complicating more than half of pregnancies. Recurrent Pregnancy Loss (RPL) is defined as three or more pregnancies lost before the twentieth week of gestation. It is believed that abnormality in maternal immune reaction to fetus and sharing of HLA antigens might be associated with RPL. To investigate the effect of HLA-DRB1 sharing between the couples with recurrent pregnancy loss on the pregnancy outcome after leukocyte therapy. Sixty primary RPL women who were immunized and followed after therapy (30 successful and 30 unsuccessful) and their husbands formed the cases of this study. In addition, one hundred healthy women were considered as the controls. HLA-DRB1 genotypes of all the cases and controls were checked by PCR-SSP method. HLA typing indicated that the prevalence of HLA-DRB1 sharing (defined as at least one allele sharing) between the couples with unsuccessful outcomes was significantly higher compared to those with successful outcomes (63.3% vs. 23.3%, p<0.004). Moreover, HLA DRB1*07:01 allelic group was significantly more frequent in the patients with unsuccessful outcome compared to the controls (18.3% vs. 8%, p<0.04). Our results confirmed the role of HLA sharing in RPL and revealed that HLA-DRB1 typing may be a valuable prognostic factor for the leukocyte therapy outcome.

Eclampsia at 17 Weeks and 3 Days Gestation: A Diagnostic Dilemma

Eclampsia is generally preceded by preeclampsia or proteinuric hypertension after the twentieth week of gestation. Only ten cases of eclampsia were reported in the presence of a foetus before 20 weeks of gestation over a 120 year epoch. It is usually believed that preeclampsia occurring before the twentieth week of gestation tends to occur in the presence of a molar pregnancy or the presence of lupus anticoagulant in the pregnant patient. The occurrence of eclampsia in a multiparous patient all of whose previous pregnancies were by the same consort and who presented at 17 weeks and 3 days gestation was an obvious diagnostic dilemma. Not only was it difficult to make the initial clinical diagnosis, it also proved quite a challenge to the histologists. After much consultation, the histologist agreed that the histology of the placenta was suggestive of a condition called placental mesenchymal dysplasia.

Matrix metalloproteinases: control of vascular function and their potential role in preeclampsia

Preeclampsia is a pregnancy specific disorder characterised by hypertension and proteinuria occurring after the twentieth week of gestation. Preeclampsia induced hypertension is the result of increased vascular reactivity and endothelial dysfunction, however, the mechanisms underlying this state remain elusive. One possible mediator may be the matrix metalloproteinases (MMPs), a family of proteinases typically recognized for long term tissue remodelling. This review examines the evidence suggesting a role for MMPs in acutely regulating vascular function. Studies have shown that MMPs can activate vasoconstrictors (e.g. endothelin), inactivate vasodilators (e.g. calcitonin gene related peptide) and transactivate cell surface receptors responsible for vasoconstriction (e.g. epidermal growth factor receptor). The potential role of these proteinases in preeclampsia will then be discussed.

Pheochromocytoma in a pregnant woman with multiple endocrine neoplasia type 2a

Pheochromocytoma is a rare cause of hypertension. Its coexistence with pregnancy is exceptional and laparoscopic removal has rarely been reported. We describe the case of a 34-year-old woman with multipleendocrine neoplasia type 2a (MEN 2a) with adrenal pheochromocytoma diagnosed in the 6th week of pregnancy. After pretreatment with phenoxybenzamine ,a successful transperitoneal laparoscopic adrenalectomywas performed in the twentieth week of gestation. The management of pheochromocytoma in pregnancy and the indications for laparoscopic surgery in pregnant patients are discussed.

Unstable angina during pregnancy in two patients with premature coronary atherosclerosis and aortic stenosis in association with familial hypercholesterolemia

Obstructive atherosclerotic coronary artery disease is uncommon in women during childbearing age, and the occurrence of myocardial ischemia during pregnancy has therefore been anecdotal. Two young patients with premature coronary arterary disease in association with familial hypercholestrolemia had unstable angina in the second trimester of pregnancy. Workup revealed coronary artery disease and aortic stenosis. One patient opted for abortion at the twentieth week of gestation, and the other decided to continue pregnancy and was delivered by cesarean at 28 weeks’ gestation. Coronary artery bypass grafting was performed after pregnancy in both patients. In addition, one of the patients underwent aortic valve replacement, and other had replacement of the narrowed ascending aorta with uneventful recovery. Our report describes an uncommon presentation of unstable angina during pregnancy in 2 young women with premature coronary artery disease and aortic valvular and supravalvular stenosis as a result of familial hypercholesterolemia. The management of these conditions during pregnancy is influenced by the effects of available therapeutic modalities on both maternal and fetal outcome. (Am J Obstet Gynecol 2000;182:1152-5.)

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Effect of a membrane depolarization on the human chorionic gonadotropin (hCG) and placental lactogen (hPL) release by placental explants

Serum human placental lactogen (HPL) was measured by a radioimmunoassay technique in 7,443 samples obtained from 1,814 pregnant women beyond their twentieth week of gestation. The pattern demonstrated by the 3,014 samples from 804 normal women confirmed the fact that abnormally low HPL values can be defined by the F-D zone (<4 μg per milliliter after 30 weeks of gestation) and these rarely occur (1.4 per cent) in normal pregnancies. The patterns in pregnancies complicated by Rh sensitization (38 women; 156 samples), diabetes mellitus (23 women; 248 samples), and hypertensive toxemia (949 women; 4,025 samples) were also studied. The major factor which appears to lower HPL values is vascular disease. In the toxemia group HPL values were more frequently depressed with multiparity and severe hypertension (BP>160/110). There was no relation noted between the presence of albuminuria in primiparous toxemia and the level of HPL in maternal serum. It would appear that the measurement of HPL in women with potential vascular disease will help to identify those with concurrent abnormal placental function.

Rudimentary horn pregnancy associated with pre-eclampsia

The unusual association of pre-eclampsia with a pregnancy in the rudimentary horn of the uterus in a multigravid patient is reported. The infrequent development of rudimentary horn pregnancy beyond the twentieth week of gestation may explain the rarity of this complication. The possible effect of rapid distension of the rudimentary horn with exposure of the myometrial surface to overwhelming fetal antigenic proteins may be of relevance in the development of pre-eclampsia in this case.

Pregnancy surveillance with Doppler velocimetry of uterine and umbilical arteries

Previous studies with Doppler velocimetry have demonstrated a strong correlation between abnormal waveforms and fetal-maternal disease. This study was designed to evaluate the potential role of Doppler velocimetry as a screening test in routine prenatal care. Two hundred fifty-five pregnant women had routine monthly Doppler (systolic/end-diastolic ratio) studies on the uterine and umbilical arteries starting in the twentieth week of gestation. When a cutoff value of 3 was used at 30 weeks for the umbilical arteries, there were 35 (13%) positive tests. In 20 of these values fell to less than 3 in the ensuing weeks and were considered false positive. The remaining 15 babies demonstrated positive clinical pathologic correlates. When a value of 2.6 was used at 26 weeks for uterine arteries, there were nine positive results, seven of which had clinical pathologic correlates. This study suggested an overall positivity rate of 7%; therefore it provides encouragement for a larger venture in which screening and impact on decision making are evaluated.

Hematologic values and lymphocyte subsets in fetal blood.

Hematologic values and lymphocyte subpopulations were determined in normal fetal blood during the second trimester of gestation. In these samples the platelet, erythrocyte, and leukocyte counts were significantly lower than in adults. Large red blood cells with a high hemoglobin content were present. Before the twentieth week of gestation, erythroblasts made up about half of the nucleated elements. Lymphocytes formed most of the leukocytes, and their absolute numbers were comparable to those in adults. Most of the fetal blood lymphocytes expressed T- or B-cell surface differentiation antigens. The percentage of T-cells was lower and that of B-cells was higher than in the adult. A high OKT4/OKT8 ratio was present. It was due to a low percentage of OKT8-positive cells. Lymphocytes with a natural killer cell phenotype were rare. Most lymphocytes were OKT10 positive, but almost none reacted with the antithymocyte antibody OKT6. These results give additional information about the development of blood cells in early human life. They can be used as reference values for the prenatal diagnosis of hereditary or acquired anomalies of the hematologic and immunologic systems.

Uterine artery Doppler velocimetry: The significance of divergent systolic/diastolic ratios

Continuous wave Doppler studies were carried out on both uterine arteries in 71 pregnant women from the twentieth week of gestation onward. Analysis of the waveform included the systolic/diastolic ratio and the presence or absence of a diastolic notch. In the current study, these ratios from 31 women with left/right systolic/diastolic difference, (between left and right uterine arteries) were compared with those of women having normal ratios. A normal left/right systolic/diastolic ratio difference of 0.3 with SD of 0.3 was found. When the left/right difference was plotted against the left/right averaged systolic/diastolic ratio, a correlation coefficient of 0.7 was noted (p less than 0.001). Significant outcome differences were noted between normal and abnormal left/right difference systolic/diastolic ratios in the perinatal parameters of gestational age at delivery, fetal weight, pregnancy-induced hypertension, proteinuria, and intrauterine growth retardation. Divergent uterine artery ratio findings are a result of one artery being the dominant supplier to the placenta. The majority of women with an elevated systolic/diastolic ratio seem to have divergent uterine blood supply to the uterus and placenta. These data suggest that errors in placentation site contribute to the development of preeclampsia and growth retardation in the fetus.

3 Chromosome analysis on chorionic villi

Chromosome abnormalities are a major health problem. About 25% of mentally retarded individuals have a chromosome aberration. Very little is known about the causes of non-disjunction giving rise to trisomies, the largest group of chromosomally abnormal individuals. As primary prevention is not possible methods have been developed to study fetal chromosomes with the aim of aborting affected fetuses. Most of the studies have involved screening of women 35 years and older--they have also allowed couples with translocations and other aberrations, who would otherwise fear to reproduce, to achieve a normal family. Hitherto, one of the greatest problems of fetal diagnosis has been the timing of the test in the second trimester of pregnancy with the risk of having to terminate a wanted pregnancy around the twentieth week of gestation. The first trimester approach would overcome this problem. PREVALENCE OF CHROMOSOME ABERRATIONS Chromosome aberrations can be diagnosed by cytogenetic analysis of metaphases from lymphocyte cultures or fibroblast cultures from skin or other tissues, amniotic fluid cell cultures or recently by a direct method or cultures from chorionic villi. Chromosome abnormalities are found with an average incidence of 6 per 1000 live births. The majority of chromosome aberrations at birth are aneuploidies due to a non-disjunctional event. The birth prevalence of viable trisomies rises with advanced maternal age. About 0.3% are chromosomal rearrangements, most of them balanced without phenotypical effect. Only a minority have unbalanced rearrangements with more or less severe developmental abnormalities. Inherited translocations have a high risk of unbalanced offspring depending on the type of rearrangement and in certain cases on the sex of the carrier parent. In sporadic aberrations the recurrence risk is about 1% (Stene and Mikkelsen, 1984). A much higher prevalence of chromosome aberrations was observed in spontaneous abortions (Hassold et al, 1980). Also, studies of perinatal deaths show a higher prevalence of chromosome aberrations compared to live birth figures (Kuleshov, 1976).

Human fetal borreliosis, toxemia of pregnancy, and fetal death

Case 1: A 24 year old woman (G 1, P 0, Ab 0) delivered a 2500 gram stillborn male fetus at term. Her prenatal care record was negative for factors associated with high risk pregnancy. No infections were diagnosed during the prenatal period. Case 2: A 22 year old woman (G 1, PO, Ab 0) delivered a 514 gram stillborn macerated female fetus at nineteen weeks gestation. Her antepartum course was complicated by toxemia of pregnancy which had its onset during the seventeenth week of pregnancy and was manifest by hypertension, albuminuria, facial edema, and peripheral edema. No infections wer diagnosed during the prenatal period. Case 3: A 37 year old woman (G 3, P 0, Ab 2) delivered a 490 gram stillborn male fetus showing mild maceration at twenty three weeks gestation. She had a chronic collagen disease in clinical remission during the pregnancy. The collagen disease was marked by episodes of fever, thrombocytopenia, anemia, arthritis, and lymphadenopathy and had been controlled with low dose oral prednisone. The patient was not receiving prednisone during the antepartum period. Amniocentesis was performed at the twentieth week of gestation and revealed a normal fetal karyotype. Toxemia of pregnancy had its onset during the twenty second week of gestation and was manifest as hypertension, and proteinuria. No infections were diagnosed during the prenatal period. Case 4: A 32 year old woman (G 2, P 0, Ab 1) delivered an 85 gram female fetus showing mild maceration at 15 weeks gestation. Her antepartum clinical record revealed no factors for a high risk pregnancy. No infections were diagnosed during the antepartum period.

Complete heart block in a fetus associated with maternal Sjögren's syndrome

This report illustrates the case of a fetus who was diagnosed by M-mode echocardiography, at the twentieth week of gestation, as having a complete heart block. The mother had a positive antinuclear antibody test result with antibodies directed against the Ro (SSA) and La (SSB) antigen system consistent with the diagnosis of Sjögren's syndrome. Management and outcome of the pregnancy are discussed.