Risk assessment adjusted for gestational age in maternal serum screening for Down's syndrome.

OBJECTIVE--To investigate the relation between errors in calculation of gestational age and assessment of risk of Down''s syndrome and to analyse the implications for screening programmes. DESIGN--Retrospective analysis of dating of gestational age by menstrual history v ultrasound scan. Computer program with maternal age and concentrations of alpha fetoprotein and free beta human chorionic gonadotrophin to calculate risk for a range of expected dates of delivery. Computer simulated prospective application of new screening programme. SETTING--Teaching hospitals in Nottingham. SUBJECTS--31,561 women with singleton pregnancies with gestational age based on routine ultrasound scan. Computer simulation of 20,000 women in three age ranges (up to 37; up to 40; all). MAIN OUTCOME MEASURES--Distribution of error between gestational age based on ultrasound scan v menstrual history. Proportion of women in the population who require precise dating of pregnancy; proportion of women who require amniocentesis. RESULTS--With gestational age derived from ultrasound scan as reference the 95% confidence interval for gestational age by menstrual history was -27 to +9 days. A screening programme for Down''s syndrome for women up to age 40 would yield a low risk (< 1:250) for this range of days in 86.0% of cases. The 14.0% of women remaining would have one or more high risk values in their report and would thus require an ultrasound scan for precise dating of the pregnancy; 30% of these--that is, 3.7% of the screened population--would be identified as high risk and require consideration for amniocentesis. CONCLUSIONS--Screening programmes for Down''s syndrome require the facility for precise dating of pregnancy to improve the accuracy of risk assessment. This can be achieved without introducing additional scans for early dating in the whole population but by selecting only those cases (about 14%) when an error in dates is likely to affect the risk of Down''s syndrome.     

Preterm or Not – An Evaluation of Estimates of Gestational Age in a Cohort of Women from Rural Papua New Guinea

BackgroundKnowledge of accurate gestational age is required for comprehensive pregnancy care and is an essential component of research evaluating causes of preterm birth. In industrialised countries gestational age is determined with the help of fetal biometry in early pregnancy. Lack of ultrasound and late presentation to antenatal clinic limits this practice in low-resource settings. Instead, clinical estimators of gestational age are used, but their accuracy remains a matter of debate.MethodsIn a cohort of 688 singleton pregnancies from rural Papua New Guinea, delivery gestational age was calculated from Ballard score, last menstrual period, symphysis-pubis fundal height at first visit and quickening as well as mid- and late pregnancy fetal biometry. Published models using sequential fundal height measurements and corrected last menstrual period to estimate gestational age were also tested. Novel linear models that combined clinical measurements for gestational age estimation were developed. Predictions were compared with the reference early pregnancy ultrasound (<25 gestational weeks) using correlation, regression and Bland-Altman analyses and ranked for their capability to predict preterm birth using the harmonic mean of recall and precision (F-measure).ResultsAverage bias between reference ultrasound and clinical methods ranged from 0–11 days (95% confidence levels: 14–42 days). Preterm birth was best predicted by mid-pregnancy ultrasound (F-measure: 0.72), and neuromuscular Ballard score provided the least reliable preterm birth prediction (F-measure: 0.17). The best clinical methods to predict gestational age and preterm birth were last menstrual period and fundal height (F-measures 0.35). A linear model combining both measures improved prediction of preterm birth (F-measure: 0.58).ConclusionsEstimation of gestational age without ultrasound is prone to significant error. In the absence of ultrasound facilities, last menstrual period and fundal height are among the more reliable clinical measures. This study underlines the importance of strengthening ultrasound facilities and developing novel ways to estimate gestational age.     

Screening for small for dates fetuses: a controlled trial.

In the hope of reducing perinatal risks associated with retardation of intrauterine growth a previously described two stage ultrasound screening schedule was evaluated by a controlled trial in 877 women with low risk single pregnancies. The two stages of ultrasound examination were an assessment of gestational age during early pregnancy followed by measurement of length from crown to rump and area of trunk at between 34 and 36 weeks'' gestation. The product of crown to rump length and trunk area was calculated. The sensitivity of this schedule in identifying in advance 94% of babies who were small for dates at birth, with 90% specificity, and the speed and simplicity of measurement confirmed the accuracy and feasibility of two stage ultrasonography as a screening procedure. The controlled trial did not, however, show any benefit from its routine application in these low risk pregnancies.     

Estimating Gestational Age in Late Presenters to Antenatal Care in a Resource-Limited Setting on the Thai-Myanmar Border

Estimating gestational age in resource-limited settings is prone to considerable inaccuracy because crown-rump length measured by ultrasound before 14 weeks gestation, the recommended method for estimating gestational age, is often unavailable. Judgements regarding provision of appropriate obstetric and neonatal care are dependent on accurate estimation of gestational age. We determined the accuracy of the Dubowitz Gestational Age Assessment, a population-specific symphysis-fundal height formula, and ultrasound biometry performed between 16 and 40 weeks gestation in estimating gestational age using pre-existing data from antenatal clinics of the Shoklo Malaria Research Unit on the Thai-Myanmar border, where malaria is endemic. Two cohorts of women who gave birth to live singletons were analysed: 1) 250 women who attended antenatal care between July 2001 and May 2006 and had both ultrasound crown-rump length (reference) and a Dubowitz Gestational Age Assessment; 2) 975 women attending antenatal care between April 2007 and October 2010 who had ultrasound crown-rump length, symphysis-fundal measurements, and an additional study ultrasound (biparietal diameter and head circumference) randomly scheduled between 16 and 40 weeks gestation. Mean difference in estimated newborn gestational age between methods and 95% limits of agreement (LOA) were determined from linear mixed-effects models. The Dubowitz method and the symphysis-fundal height formula performed well in term newborns, but overestimated gestational age of preterms by 2.57 weeks (95% LOA: 0.49, 4.65) and 3.94 weeks (95% LOA: 2.50, 5.38), respectively. Biparietal diameter overestimated gestational age by 0.83 weeks (95% LOA: -0.93, 2.58). Head circumference underestimated gestational age by 0.39 weeks (95% LOA: -2.60, 1.82), especially if measured after 24 weeks gestation. The results of this study can be used to quantify biases associated with alternative methods for estimating gestational age in the absence of ultrasound crown-rump length to inform critical clinical judgements in this population, and as a point of reference elsewhere.     

Alpha-fetoprotein in Abortion

The clinical value of maternal serum alpha-fetoprotein (AFP) as a guide to the outcome of threatened abortion was assessed. After the thirteenth week of gestation, abortion occurred more frequently (10/12) in women with abnormal serum AFP levels than in those (2/12) whose AFP concentrations were within the normal range. Low levels were present in women with blighted ovum and high concentrations were associated with intrauterine fetal death. In legal first and second trimester abortions, the circulating maternal AFP levels in postabortion samples were often higher than before abortion, irrespective of whether abortion was performed instrumentally or induced with prostaglandins. Maternal serum AFP levels provide a new means for prediction of the outcome of threatened abortion.     

alpha-Fetoprotein values in monkey (Macaca mulatta) pregnancy.

The pregnant rhesus monkey's (Macaca mulatta) potential as a model for understanding the dynamics of alpha-fetoprotein (AFP) metabolism in human pregnancy was evaluated. AFP levels in maternal and fetal serum and amniotic fluid were determined by radioimmunoassay. Significant correlations were found between decreasing maternal serum, fetal serum and amniotic fluid AFP concentrations and increasing gestational age. However, these data are not consistent with the AFP changes reported in human pregnancy. It appears that this animal has limited applicability as a model in this aspect of human pregnancy.     

经阴道超声联合血清AFP、PAI-1及MMIF对子宫内膜异位症的诊断价值分析

摘要 目的：探讨经阴道超声联合血清甲胎蛋白（AFP）、纤溶酶原激活物抑制物1（PAI-1）及巨噬细胞移动抑制因子（MMIF）对子宫内膜异位症的诊断价值。方法：选取我院2021年8月到2023年8月收治的150例子宫内膜异位症患者进行回顾性分析,分析其经阴道超声检查图像特征,并以病理诊断作为"金标准",分析阴道超声对宫内膜异位症的阳性检出率。依照子宫内膜异位症分期,将其分为Ⅰ~Ⅱ期组（n=77）,Ⅲ~Ⅳ期组（n=73）,另选取同期来我院体检的150例健康女性作为对照组。分析三组受检者血清AFP、PAI-1及MMIF表达水平,并采用Spearman相关分析法分析AFP、PAI-1及MMIF与子宫内膜异位症的相关性。最后建立受试者特征（ROC）工作曲线分析经阴道超声联合血清AFP、PAI-1及MMIF对子宫内膜异位症的诊断效能。结果：150例子宫内膜异位症患者均经病理诊断确诊,通过经阴道超声检查确诊为子宫内膜异位症的患者128例,85.33%。其中75例患者为卵巢型,超声显示巨大巧克力囊肿,内部可见大量细密点状回声与分隔光带。53例患者为子宫型,超声显示后壁腺肌瘤,内部回声不均匀,可见片状无回声区域;三组受检者血清AFP、PAI-1及MMIF表达水平对比差异显著,Ⅲ~Ⅳ期组明显高于Ⅰ~Ⅱ期组和对照组,差异具有统计学意义（P＜0.05）;Spearman相关分析结果显示：AFP、PAI-1及MMIF与子宫内膜异位症呈正相关（P＜0.05）;诊断灵敏度和特异度从低到高依次为MMIF（52.58%、64.32%）、PAI-1（60.03%、67.53%）、AFP（65.24%、71.27%）、经阴道超声（73.25%、86.36%）、经阴道超声联合血清AFP、PAI-1及MMIF（84.26%、98.63%）。经阴道超声联合血清AFP、PAI-1及MMIF的诊断灵敏度明显高于单一指标诊断（P＜0.05）。结论：经阴道超声联合血清AFP、PAI-1及MMIF对子宫内膜异位症的诊断价值较高,其灵敏度和特异度分别为84.26%、98.63%,通过联合诊断可进一步辅助减少子宫内膜异位症的误诊和漏诊几率,为子宫内膜异位症的诊断与治疗提供重要参考。     

Screening for fetal malformations using ultrasound and measurements of alpha-fetoprotein in maternal serum.

Fetal ultrasound combined with semiquantitative measurements of alpha-fetoprotein in maternal serum was used for early detection of neural tube defects and omphalocele in 10 147 pregnancies. The accurate assessment of gestational age, obtained by ultrasound, facilitated evaluation of alpha-fetoprotein concentrations in selecting cases for amniocentesis. The advantage of screening with two independent methods is suggested by the finding that eight out of 10 cases with malformations (spina bifida, encephalocele, anencephalus, omphalocele) were detected when both methods were used. Screening by routine ultrasound alone detected only four malformations and by measurement of alpha-fetoprotein alone only seven. The results suggest that, in a low risk population, ultrasound should be combined with the measurement of alpha-fetoprotein in screening for neural tube defects. Measurement of alpha-fetoprotein is indispensable in detection of the small neural tube defects, where the fetus would survive with severe sequelae. The semi-quantitative analysis of alpha-fetoprotein that may be used in combination with ultrasound examination is of negligible cost.     

Biological roles of alpha-fetoprotein during pregnancy and perinatal development

The use of alpha-fetoprotein (AFP) as a serum marker in cancer actually predates its employment in the detection of congenital defects; however, the latter use of AFP as a fetal defect marker has propelled its clinical utilization. Although the serum-marker capacity of AFP has long been exploited, less is known of the biological activities of this oncofetal protein during fetal and perinatal development. In the present review, the biological activities of AFP are discussed in light of this glycoprotein's presence in various biological fluid compartments: embryonic and fetal tissues, serum, urine, and reproductive fluids. After a review of the histochemical detection of AFP in various cells and tissues during development, AFP concentrations within various biological fluids were discussed in the context of gestational age and anatomic location. Discussion follows concerning the relationships and roles of AFP in developmental events such as erthyropoiesis, histogenesis/organogenesis, and ligand binding and in developmental disorders such as hypothyroidism, folate deficiencies, and acquired immunodeficiency disorder (AIDS). Based on its association with so many types of birth defects, malformations, and congenital anomalies, AFP can be viewed as a molecular "troubleshooter" until signal transduction pathways are established during pregnancy and prenatal development. The review concludes with a discussion of the place of AFP in the rapidly expanding field of proteomics.     

Increased circulating heat shock protein 70 (HSPA1A) levels in gestational diabetes mellitus: a pilot study

Recent data indicate that serum Hsp70 (HSPA1A) levels are increased in type 1 and 2 diabetes mellitus. However, there is no report in the literature on circulating Hsp70 levels in gestational diabetes mellitus. In this pilot study, we measured serum Hsp70 levels in 11 pregnant women with pregestational diabetes, 38 women with gestational diabetes, and 40 healthy pregnant women with ELISA. Plasma glucose levels, serum insulin concentrations, HbA1c values, and the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were also determined. According to our results, serum Hsp70 concentrations were significantly higher in women with pregestational and gestational diabetes mellitus than in healthy pregnant women. In addition, pregestational diabetic women had significantly higher Hsp70 levels than those with gestational diabetes. Furthermore, in the group of women with gestational diabetes mellitus, serum Hsp70 levels showed a significant positive correlation with HbA1c values. However, there was no other relationship between clinical features and metabolic parameters of the study subjects and their serum Hsp70 levels in either study group. In conclusion, we demonstrated for the first time in the literature that serum Hsp70 levels are increased and correlate with HbA1c values in women with gestational diabetes mellitus. Nevertheless, further studies are needed to determine whether circulating Hsp70 plays a causative role in the pathogenesis of gestational diabetes or elevated serum Hsp70 levels are only consequences of the disease.     

Alpha fetoprotein levels in newborn infants with reference to sex, gestational age and birth weight

Alpha fetoprotein (AFP) concentration was higher in the mature full term male infants than age matched females. An inverse correlation, at birth, between cord serum AFP level and duration of pregnancy was observed. In contrast no correlation between body weight and AFP levels exists in babies of either sex at identical gestational age.     

Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism.

Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate.     

Pregnancy hormone concentrations in marijuana users

The maternal serum concentrations of human chorionic gonadotropin, pregnancy-specific beta-l-glycoprotein, placental lactogen, progesterone, 17-hydroxyprogesterone, estradiol and estriol were measured in 13 women who smoked marijuana regularly throughout pregnancy. Cannabinoid use in these women was confirmed by RIA measurements of their sum Δ ⁹- tetrahydrocannabinol (THC) concentrations. These THC using women were matched within $\text{2}\text{1}\text{2}$ weeks of gestational age with 13 pregnant non-THC using controls drawn from the same population. Placental protein and steroid hormone concentrations were within established normal ranges for gestational age and there were no significant differences between the groups in the concentrations of any of the protein and steroids measured. In addition, no significant differences between THC users were found following linear regression analysis of placental hormone concentrations as a function of gestational age. Thus, this study suggests that marijuana use during pregnancy does not significantly alter the circulating maternal concentrations of trophoblastic protein hormones or major fetoplacental steroid hormones.     

Secretion and glycosylation of alpha-foetoprotein by the mouse yolk sac.

Secretion and glycosylation of alpha-foetoprotein (AFP) by mouse yolk sac were studied by using yolk-sac explants cultured in vitro. Yolk-sac explants rapidly incorporated [35S]methionine into AFP, whereas radioactively labelled AFP was not found in the medium until 30 min after incubation was initiated. Electrophoretic analysis revealed that microheterogeneity of AFP synthesized in explants increased in parallel with the gestational age of the yolk sacs. The change in microheterogeneity was noted by the formation of increasingly acidic forms. Only the most acidic forms of AFP were found to be present in the medium on each gestational day studied. Tunicamycin reduced the incorporation of glucosamine into AFP with a concomitant decrease in molecular weight and microheterogeneity. However, the relative amount of AFP released into the medium was not altered by the presence of tunicamycin. The presence of under-glycosylated AFP in the medium indicates that glycosylation of AFP is not essential for its secretion from the yolk sac. In light of these and previous findings, it is suggested that the glycosylation of AFP may be important for the turnover of this glycoprotein in serum.     

Lower interleukin-2 and higher serum tumor necrosis factor-a levels are associated with perimenstrual, recurrent, facial Herpes simplex infection in young women

The aim of this study was to look at a possible relationship between the recurrent perimenstrual dermatosis - facial Herpes simplex infection and the serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-alpha). Twenty-one volunteers (19-26 year olds) were examined at five points of the menstrual cycle. Ten volunteers were characterised by recurrent Herpes simplex infection lasting either from the 18th or the 25th day of the menstrual cycle until a few days after menstruation. Eleven young women without symptoms formed the control group. Both groups were similar as regards blood levels of 17beta-estradiol and progesterone. The group with the frequent infectious symptoms was characterised, however, by lower concentrations of IL-2 throughout the whole menstrual cycle, as compared to those without the symptoms. Levels of IL-2 in this group additionally dropped significantly on the 18th and on 25th day of the cycle. Moreover, the group with symptoms was characterised by higher level of TNF-alpha on the 18th day. These changes were found during the menstrual cycle of the women with recurrent herpes infection who however, at the time of the examination were free of the clinical symptoms. There was a similar tendency in both groups towards an increase in the levels of TNF-a around menstruation. Measurement of the other serum pro-inflammatory marker - IL-6 showed higher levels of this cytokine during the menstrual cycle in the group with the clinical symptoms. The results indicate that a decrease of IL-2 together with an increase of TNF-alpha and IL-6 in the serum seem to be related to recurrent perimenstrual Herpes simplex infection.     

Significance of the maternal levels of serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol in various congenital developmental defects in pregnancy trimester II]

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) concentrations were measured in maternal serum samples from 21 pregnancies with neural-tube defects, 4 pregnancies with ventral wall defects (VWD) and 1662 unaffected pregnancies in women. These congenital malformations were confirmed by ultrasound scanning. The mean multiplate of the median (MoM) for AFP and uE3 was significantly different from the control values in cases of open NTD (AFP median MoM = 5.95, p < 0.001, uE3 median MoM = 0.2, p < 0.001), while hCG values did not differ from those of matched controls (hCG median MoM = 0.9). The biological basis of altered levels of uE3 in pregnancies with fetal NTDs is unclear.     

Maternal serum alpha-fetoprotein levels in multiple pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were higher in 10 twin pregnancies and one triplet pregnancy than in 22 control singleton pregnancies matched for maternal age, parity, and the time of gestation at which the serum sample was taken. In twin pregnancies the average AFP levels were double those found in singleton pregnancies and the level in the triplet pregnancy was even higher. Raised maternal serum AFP values due to multiple pregnancy should not cause unnecessary amniocentesis in the diagnosis of anencephaly or spina bifida if an ultrasound investigation is routinely performed first.     

Level of estradiol and progesterone in blood serum during the menstrual cycle in woman with acute hepatitis b]

The study was aimed at the determination of blood serum levels of the ovarian hormones (estradiol and progesterone) in women during the first menstrual cycle occurring in the course of hospitalization because of the acute viral hepatitis of type B, and in the same women during the first menstrual cycle occurring in the course of early convalescence after leaving the hospital. The observed group consisted of 20 women of age between 18 and 35 years treated because of acute hepatitis without coexisting diseases including gynecological ailments. All the women had a regular 28-day menstrual cycle. Twenty healthy women served as a control group. The blood serum concentrations of estradiol and progesterone were determined in all the subjects on 6-th, 12-th, 14-th, 18-th and 22-nd day of the menstrual cycle by RIA method using the ready made reagent kits. A significant decrease in the mean value of estradiol was found in the group of sick women as compared to the control group and to the same group of women in the course of early convalescence. On the other hand the value obtained during the first menstrual cycle after discharge from the hospital did not differ from that observed in healthy women. Mean value of blood serum progesterone concentration was higher in sick women than those in the control group and in the same women during convalescence all the time except on the 22-nd day of the cycle. These values did not differ significantly when comparing the group of sick women during convalescence and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of ultrasound to monitor prenatal growth and development in the common marmoset (Callithrix jacchus)

The increasing use of non-human primates to study fetal development and neonatal management has necessitated the availability of fetuses of known gestational history. In this study, prenatal development and growth were investigated in the common marmoset (Callithrix jacchus) using ultrasound. The objectives of this study were: (1) to determine the accuracy of ultrasound for monitoring prenatal growth and development in common marmosets, (2) to determine if litter size influences prenatal growth trajectories, and (3) to assess growth discordancy among litter mates. Fifty pregnancies were monitored longitudinally using real-time abdominal sonography. During each examination the number of fetuses was recorded, and crown-rump length (CRL) and biparietal diameter (BPD) were measured. The results indicate that ultrasound is a reliable method for observation of gross morphological changes during prenatal development in this species. Measures of CRL and BPD taken early in gestation using ultrasound were in agreement with those from gross specimens. Triplets were significantly (P < 0.05) smaller than twins for both BPD and CRL. No significant relationship was found between litter size and within litter variation in CRL or BPD. This study is the first longitudinal investigation of prenatal growth and development in C. jacchus. The observations from this study will be of use for determining approximate gestational age of fetuses, as well as providing guidelines for routine monitoring of pregnancy in this species. © 1995 Wiley-Liss, Inc.     

Gender influence on jejunal migrating motor complex

The role of gender and the menstrual cycle in small bowel motility has not been clearly elucidated. Jejunal motility was recorded with a nasojejunal catheter incorporating five solid-state pressure transducers in ambulatory menstruating women and men of comparable age over 24 h. All women were studied twice, in the early follicular (early-F) and midluteal (mid-L) phases of the menstrual cycle, verified by determining serum levels of gonadal steroids and gonadotropins. The propagation velocity of phase III was slow and the contraction amplitude was high in both menstrual cycle phases compared with men, and these parameters were correlated with serum estrogen levels in the mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle duration during sleep was long compared with other groups and positively correlated with estrogen concentrations, whereas in the mid-L phase MMC cycle duration during sleep was negatively correlated with serum progesterone levels. In all groups, the frequency of phase III contractions was low and the intercontractile interval measured from pressure peak to peak was long during sleep compared with the awake state. Postprandial motility did not display gender difference in any parameter examined. The results demonstrate that the majority of patterns of motility are similar in menstruating women and men, whereas certain aspects of the MMC, most conspicuously propagation velocity and phase III contraction amplitude, differ. We have also documented circadian variation of phase III contraction frequency in both women and men.