The relationship between maternal serum alpha-fetoprotein and maternal haemoglobin

OBJECTIVES: To test the hypothesis that both second-trimester maternal serum alpha-fetoprotein (MSAFP) levels and Down syndrome-screening test are related to maternal haemoglobin concentration. METHODS: Three hundred and seventeen women in three groups according to their haemoglobin levels: normal haemoglobin concentration (between 10.5 and 13.2 g/dL) (n = 262; 82.6%), anaemia (less than 10.5 g/dL) (n = 11; 3.5%), or high haemoglobin levels (greater than 13.2 g/dL) (n = 44; 13.9%) were studied. MSAFP and Down syndrome risk (on the bases of maternal age, MSAFP and maternal serum beta-hCG concentrations) were recorded. RESULTS: MSAFP (MoM) was lower in women with high haemoglobin levels (0.79 MoM (0.66-1.14)) (p = 0.001) than in women with normal haemoglobin concentrations (1.00 MoM (0.81-1.26)). It was also decreased in women with anaemia (0.90 MoM (0.65-0.94)), even though the difference with women with normal haemoglobin levels was of borderline statistical significance (p = 0.06). The Down syndrome risk was higher in both anaemic women (1:850 (1:380-1:1400)) (p = 0.009) and women with high haemoglobin levels (1:1425 (1:460-1:3100)) (p = 0.036) than in women with normal haemoglobin concentration (1:1950 (1:800-1:5000)). A quadratic model was the best predictive model for both MSAFP (p = 0.02) and Down syndrome risk (p = 0.001) when considering maternal haemoglobin as the independent variable. CONCLUSIONS: MSAFP is decreased and Down syndrome risk is increased in both anaemic and pregnant women with high haemoglobin concentration. Further studies are needed to establish whether adjustments for maternal haemoglobin are needed when giving Down syndrome risks based on biochemical markers. Copyright 2004 John Wiley & Sons, Ltd.     

Elevated second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal down syndrome and other chromosomal abnormalities

SUBJECTS: To evaluate second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal Down syndrome and other chromosomal abnormalities. METHODS: Inhibin A level was measured from the serum samples of 25 chromosomally abnormal pregnancies, including 15 cases of Down syndrome, 4 cases of trisomy 18, 1 case of trisomy 13, and 5 cases of sex chromosome aneuploidies (4 cases of 47,XXY and 1 case of 45,X) and in a cohort of 150 controls during the second trimester of pregnancy. RESULTS: The multiple of median levels of Down syndrome (1.74) and other chromosomally abnormal pregnancies (2.03) are significantly higher than that of normal pregnancies (p = 0.002 and p = 0.024, respectively). Only 3 of 15 (20%) Down syndrome cases had inhibin A levels at or above the 95th centile of the control values. CONCLUSIONS: Inhibin A levels are raised in Asian women affected with fetal Down syndrome and sex chromosome abnormality. In spite of the poor discrepancy of inhibin A, it might be a potential marker for Down syndrome screening in Asians.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1.8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.     

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.     

Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome

In a group of 26 524 control pregnancies and a group of 3728 pregnancies affected by one or more of the pregnancy complications of low birthweight, intra-uterine growth restriction (IUGR), preterm delivery and stillbirth, I have compared the relative risk of occurrence of these complications in pregnancies which had a raised maternal serum AFP (>2.0 MoM), raised maternal serum free beta-hCG (>2.0 MoM), low AFP (<0.5 MoM), low free beta-hCG (<0.5 MoM), combined raised AFP and free beta-hCG (>2.0 MoM), and in those with an increased Down syndrome risk (1 in 250 or greater). In the low birthweight group, only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.1. In the IUGR group, also only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.3. In the preterm delivery group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 3.8, 1.8 and 6.2. In the stillbirth group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 4.5, 2,4 and 7.2. An isolated raised free beta-hCG or an increased Down syndrome risk were not associated with an increased relative risk for any of the pregnancy complications investigated. However, apart from the six to seven-fold increased risk when both AFP and free beta-hCG are above 2.0 MoM, suggesting increased risk of preterm delivery or impending fetal death, the clinical utility of such significant differences is probably poor.     

Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes

OBJECTIVES: We sought to determine the types of congenital anomalies affecting infants of women with gestational diabetes mellitus or type 2 diabetes and to examine the relationship between those malformation types and measures of initial glycemia of women at entry into prenatal care with type 2 diabetes or at time of diagnosis in women with gestational diabetes mellitus. STUDY DESIGN: A total of 4,180 pregnancies complicated by gestational diabetes mellitus (n = 3764) or type 2 diabetes (n = 416) that were delivered after 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as being absent, minor, major, genetic syndromes, or aneuploidies. Major anomalies were further categorized by the number and type of affected organ systems. In addition to maternal clinical and historical parameters, the initial fasting serum glucose either from the diagnostic glucose tolerance test (gestational diabetes mellitus) or at entry to prenatal care (type 2 diabetes) and the initial glycosylated hemoglobin before insulin therapy were examined for a relationship to anomalies. RESULTS: The initial fasting serum glucose and glycosylated hemoglobin levels were significantly higher in pregnancies with major (n = 143) and minor (n = 112) anomalies and genetic syndromes (n = 9) compared with pregnancies with no anomalies (n = 3895). Of those pregnancies with major anomalies, the most commonly affected organ systems were the cardiac (37.6%), musculoskeletal (14.7%), and central nervous systems (9.8%) and anomalies involving multiple organ systems (16%). There was no increased predominance of any specific organ system involvement seen with increasing fasting serum glucose levels in pregnancies with major congenital anomalies. Pregnancies with major anomalies affecting multiple organ systems had significantly higher initial fasting serum glucose levels (166 +/- 64 mg/dL) compared with pregnancies in which one organ system was affected (141 +/- 55 mg/dL, P <.04) or no organ systems were affected (115 +/- 38 mg/dL, P <.0001). CONCLUSION: Congenital anomalies in offspring of women with gestational and type 2 diabetes affect the same organ systems that have been previously described in pregnancies complicated by type 1 diabetes. Increasing hyperglycemia at diagnosis or presentation for care was associated with an increasing risk of anomalies in general and with anomalies involving multiple organ systems without a preferential increase in involvement of specific organ system.     

First trimester aneuploidy screening combining biochemical and ultrasound markers

The different strategies applied for Down syndrome (DS) screening in a single center are presented and the results are analyzed taking into account the number of invasive procedures needed for the diagnosis of one affected pregnancy. The use of advanced maternal age as a single criterion, from 1980 to 1992 proved to be poorly effective since 102 amniocentesis are needed to diagnose one DS affected pregnancy (1:102) or 52 to diagnose any aneuploidy (1:52) With the use of second trimester screening with serum markers (AFP and hCG) at 14-18 weeks in 8711 women less than 38 years, from 1993 to 1999 the ratios were improved to 1:82 and 1:47 respectively. With the introduction of the combined test in 1999 using free hCG, PAPP-A (sampling at 9-10 weeks) and NT (measured at 12 weeks) in 3644 women under 38 years, and gestational weeks adjusted by US in 3644 singleton pregnancies with complete follow-up, the ratios were substantially improved to 1:16 procedures for DS or 1:8 for any aneuploidy. The detection rate achieved was 90% for a false positive rate of 3.4%. Comparing the different strategies applied in our Unit it is clear that the combined test applied in the first trimester provides a substantial improvement in detection rates and reduction of unnecessary invasive testing.     

First trimester maternal serum vitamin D and markers of preeclampsia

Abstract

Objective: There is evidence that vitamin D deficiency is associated with preeclampsia. The aim of the study was to determine if maternal levels of vitamin D at 1st trimester were related to markers of preeclampsia.

Material: Serum levels of 25-hydroxy-vitamin D (25OHD), PAPP-A, PlGF, uterine artery pulsatility index and mean arterial pressure were measured in 280 pregnant women.

Results: Preeclampsia markers were not related to 25OHD concentration.

Conclusion: First trimester maternal serum concentration of vitamin D does not seem to be connected with markers of preeclampsia.     

The relationship of maternal antibody levels to post-cesarean section endometritis

One hundred eight pneumococal polysaccharide antibody levels were determined by radioimmunoassay preoperatively in 18 patients who underwent elective repeat cesarean section. Eight patients developed post-cesarean section endometritis, and 10 did not. The endometritis group did not vary significantly from the noninfected group in preoperative hematocrit, social status, number of previous pregnancies, maternal and newborn weights, length of operation, and Apgar scores. Mean antibody levels in the endometritis group were significantly lower than those in the control group (49 versus 103 ng/ml; p < 0.05). Mean antibody levels for the six serotypes in the endometritis group were significantly lower than those in the control group (p < 0.05). This study indicated that a healthy maternal immune system may play an important role in preventing post-cesarean section morbidity. Pneumococcal polysaccharide antibody levels may be used in pregnancy to assess the risk for post-cesarean section infections.     

Risk of fetal chromosomal anomalies in patients with elevated maternal serum alpha-fetoprotein.

When elevated maternal serum alpha-fetoprotein (MSAFP) results lead to diagnostic amniocentesis, a decision of whether to karyotype fetal cells must be made. We examined our experience with MSAFP screening in 71,563 unselected pregnancies in which karyotyping was performed when amniocentesis was done because of MSAFP elevations. A total of 727 women (1.0%) underwent amniocentesis because of elevated MSAFP values and among this group, seven chromosomal anomalies (incidence one in 104) were detected. Of the 727 women, 658 (91%) had normal amniotic fluid AFP. In this group, there were six (one in 109) chromosomally abnormal fetuses: three with triploidy, two with 47,XXX, and one with 46,XX,1q-. Among the 69 pregnancies with elevated amniotic fluid AFP, one fetal chromosomal anomaly (trisomy 13) was diagnosed. The incidence of all chromosomal anomalies observed in women undergoing amniocentesis because of elevated MSAFP is comparable to that reported in women 36 years of age undergoing testing because of advanced maternal age. We believe that chromosome analysis should be performed on amniotic fluid samples obtained because of elevated MSAFP unless there are compelling financial circumstances that preclude this. Even in such cases, cell cultures should be established until the amniotic fluid AFP result is available. Chromosome analysis is essential when the amniotic fluid AFP is elevated because of the known association between open fetal defects (spina bifida, omphalocele, and scalp defects) and trisomies 13 and 18.     

Association between second-trimester isolated high maternal serum maternal serum human chorionic gonadotropin levels and obstetric complications in singleton and twin pregnancies

OBJECTIVE: The purpose of this study was to examine the clinical significance of high maternal serum human chorionic gonadotropin levels in the second trimester in singleton and twin pregnancies within the Ontario maternal serum screening program. STUDY DESIGN: The study group comprised 564 women with singleton pregnancies with total maternal serum human chorionic gonadotropin levels of > or =4.0 multiples of the median (MoM) and serum marker alpha-fetoprotein levels of <2.0 MoM. The cases were matched with 1692 control subjects who had both serum marker alpha-fetoprotein levels and maternal serum human chorionic gonadotropin levels of <2.0 MoM. The second part of the study comprised 93 twin pregnancies with maternal serum human chorionic gonadotropin levels of > or =5.0 MoM and serum marker alpha-fetoprotein levels of <4.0 MoM; the control group (n = 1496) had serum marker alpha-fetoprotein levels of <4.0 MoM and maternal serum human chorionic gonadotropin levels of <5.0 MoM. The final part of the study included 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM). RESULTS: Of the singleton pregnancies with maternal serum human chorionic gonadotropin levels of > or = 14;4.0 MoM, 22.5% had severe adverse obstetric outcomes, compared with only 10.9% of the matched control population (P =.001). Women with markedly elevated maternal serum human chorionic gonadotropin levels had significantly increased risks of having spontaneous miscarriage, small-for-gestational-age infants, pregnancy-associated hypertensive disorder, and preterm delivery. Of the women with twin pregnancies with high maternal serum human chorionic gonadotropin levels (> or =5.0 MoM), 71% had at least one complication (such as miscarriage and preterm delivery) compared with 55.3% in the control group. Finally, 23 of 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM) had serious adverse outcomes (such as fetal abnormalities, pregnancy-associated hypertensive disorder, premature separation of placenta, intrauterine growth restriction, neonatal respiratory distress syndrome, and neonatal jaundice). CONCLUSION: Pregnancies with an elevated maternal serum human chorionic gonadotropin level are associated with adverse obstetric outcomes. Increased maternal and fetal surveillance is warranted in these pregnancies.     

The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities

In a first trimester study of 5422 Caucasian women, 752 Afro-Caribbean women and 170 Asian women we have shown that the median maternal serum marker MoMs for free beta-hCG and PAPP-A were 19% and 48% higher in Afro-Caribbean women and 19% higher and 35% higher in Asian women, compared to Caucasian women. Correcting for maternal weight made very little difference to the effect in Afro-Caribbeans (21% and 57% higher after weight correction) but reduced the effect in Asians (4% and 17% higher after weight correction ). It is estimated that correcting for maternal weight and ethnicity overall would increase the detection rate by a modest 1.4%. However, the effect on an individual's risk could result in as much as a two-fold increase in the patient specific risk for trisomy 21. The impact of ethnic origin seems to be greater than that observed with second trimester biochemical markers and larger studies are required in order to develop robust algorithms for correcting for ethnic origin in the first trimester.     

Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations

OBJECTIVES: To assess whether there is a need to correct first-trimester biochemical markers (free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A)) or first-trimester fetal nuchal translucency thickness (NT) in different ethnic groups, when screening for Downs syndrome at 11-14 weeks of gestation. METHODS: Free beta-hCG, PAPP-A and fetal NT were measured at 11-14 weeks of gestation in a group of women presenting for first-trimester screening in two OSCAR centres. The group comprised 61 219 sets of data from Caucasian women (the reference group); 4835 sets of data from South Asian women; 3450 sets of data from Oriental women and 2727 sets of data from Afro-Caribbean women. The Oriental data set was supplemented with a further 480 cases collected in Hong Kong and the Afro-Caribbean data set was supplemented with 216 cases collected from Kings College. The difference in marker values between the reference group and the other ethnic groups was compared before and after weight correction for the biochemical markers using standard statistical techniques. A correction factor for ethnic origin was applied for all three markers and the screen-positive rate before and after correction was assessed for the various groups. RESULTS: After maternal weight correction, in Afro-Caribbean women, the median PAPP-A was increased by 55% and the free beta-hCG increased by 11%. In south Asian women, the PAPP-A was increased by 8% and the free beta-hCG decreased by 7.5%. In Oriental women, the PAPP-A was increased by 9% and the free beta-hCG by 6%. For delta NT in Afro-Caribbean women, the values were 0.064 mm lower on average than in Caucasian women and for south Asian women 0.045 mm lower. The difference of -0.012 for Oriental women was not significant. Before correcting for ethnic origin, these changes resulted in the screen-positive rates being lower in the Afro-Caribbean group (3.7% vs 5.6%), the south Asian group (4.3% vs 5.6%) and Oriental group (4.9% vs 5.6%). After correction, the screen-positive rates were largely similar in the four groups. CONCLUSION: Differences in median PAPP-A, free beta-hCG and, to a lesser extent, in NT exist in Afro-Caribbean, South Asian and Oriental women. In populations where the medians and delta NT reference ranges are established in predominantly Caucasian populations, some correction for ethnicity is appropriate and can redress differences in screen-positive rates between these different groups.     

妊娠中期母血清生化标志物筛查唐氏综合征的临床价值

目的评价妊娠中期母血清生化标志物筛查唐氏综合征(21-三体综合征)的临床价值。方法1996年7月至2003年6月,南京市妇幼保健院用时间分辨荧光分析法对13175例妊娠14~20周的孕妇进行血清甲胎蛋白(AFP)、游离绒毛膜促性腺激素(free-β-HCG)检测,切割值1∶300,对高风险者行羊水检查。结果21-三体综合征及18-三体综合征的检出率为5.3/万,假阳性率为10.69%。唐氏综合征高风险组胎儿异常的发生率高于唐氏综合征低风险组(P<0.01)。≥35岁孕妇组胎儿异常的发生率高于<35岁孕妇组(P<0.05)。结论AFP、free-β-HCG可用于筛查唐氏综合征及胎儿异常。     

Cerebral palsy due to chromosomal anomalies and continuous gene syndromes

When cerebral palsy is defined as a disorder of movement and posture that is due to nonprogressive disturbances that occur in the developing fetal and infant brain, a significant proportion-up to 10%--is the consequence of chromosomal anomalies and continuous gene syndromes. Abnormalities of chromosomes are constitutional or acquired. Acquired chromosomal abnormalities develop postnatally, affect only one clone of cells, and are implicated in the evolution of neoplasia. Constitutional abnormalities develop during gametogenesis or early embryogenesis and affect a significant portion of the subject's cells.