First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death

Spencer, Kevin; Cowans, Nicholas J.; Avgidou, K.; Nicolaides, Kypros H.

doi:10.1002/uog.3809

Cited by 103 publications

(87 citation statements)

References 33 publications

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“…The normal pregnancy group comprised of 47 770 pregnancies and the characteristics of this group have been previously described (Spencer et al, 2006a). We identified 222 cases with pre-eclampsia and the characteristics of the cases are described in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…There is a modest increase in LR with decreasing levels of PAPP-A and in the presence of a normal karyotype such low levels, in addition to being an indicator of increased risk for preeclampsia, also indicated increased risk for other adverse pregnancy outcomes (Spencer et al, 2006a(Spencer et al, , 2007a. The presentation of data in terms of LR curves at any level of PAPP-A MoM is likely to be a more useful aid to counselling than the point estimates from previous studies Smith et al, 2002;Yaron et al, 2002;Dugoff et al, 2004;Spencer et al, 2005b), which are summarised in Table 2.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have shown an association between low first-trimester maternal serum pregnancy associated plasma protein-A (PAPP-A) levels and the subsequent development of pregnancy complications, including pre-eclampsia Smith et al, 2002;Yaron et al, 2002;Tul et al, 2003;Dugoff et al, 2004;Krantz et al, 2004;Spencer et al, 2005aSpencer et al, , 2006aSpencer et al, ,b, 2007aCowans and Spencer, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

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Background Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.Methods Maternal serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47 770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ß-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. ResultsIn the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free β-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. ConclusionsThe graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

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“…A similar increase in screening performance can be achieved by examining the additional ultrasound markers in all cases, as well as by a contingency procedure in which the fi rst-stage combined screening categorises the patients into high-, intermediate-, and low-risk categories. In such a case, the new markers are only assessed in the intermediate-risk group in order to stratify the women into either low-or high-risk (1,2,37) .…”

Section: First Trimester Screening Testsmentioning

confidence: 99%

Recommendations on prenatal screening and the connections to other diseases such as thyroid dysfunction

Springer

Potluková²,

Límanová³

et al. 2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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The aim of general maternal-foetal care is to ensure an uncomplicated birth of a healthy baby to a healthy mother. There is a large range of screening tests used during pregnancy: for gestational diabetes, infection, rhesus-D status, thyroid dysfunction, as well as other tests. An important part of prenatal care is the screening of major aneuploidies, primarily for Down ' s syndrome. This screening is possible in either the fi rst or second trimester, or in both. Management of this type of screening is very similar around the world. Hypothyroidism can affect the psychomotor development of the child. Thyroidstimulating hormone (TSH), autoantibodies against thyroperoxidase (TPOAb), and free thyroxin (FT4) were determined within our group of 7530 pregnant women. Elevated concentrations of TSH were found in 5.1 % , suppression was found in 2.9 % and 11.5 % were TPOAb positive. Either a familial or personal history of thyroid or autoimmune diseases was present in 58.3 % of those women who tested positive on any thyroid test. At minimum, 40 % of women TPOAb positive during pregnancy have some kind of thyroid disorders after delivery. These results support the effi cacy of general thyroid function screening in early pregnancy, as well as the follow-up after delivery of those women who are positive.

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“…13 Low concentrations of PAPP-A have also associated with poor obstetric outcomes such as low birth weight, pre-term delivery, spontaneous foetal loss, small for gestational age and pre-eclampsia. 7,[14][15][16][17] Few studies have looked at biochemical screening markers in instances of confirmed GDM. One study, of a small number of cases, 7 showed a significant reduction in both concentrations of PAPP-A and free hCG, whilst other studies 12,18 found either no significant effect or found a significant reduction only for PAPP-A.…”

Section: Introductionmentioning

confidence: 99%

The association between gestational diabetes mellitus and first trimester aneuploidy screening markers

Spencer

Cowans

2013

Ann Clin Biochem

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Objective: To establish whether maternal serum first trimester concentrations of PAPP-A and free hCG are altered in pregnancies that subsequently are diagnosed by an oral glucose tolerance test (OGTT) with gestational diabetes mellitus (GDM). Methods: Over the period 2009 and 2011, the results for women who had first trimester screening for aneuploidy were matched with those having an oral glucose tolerance test at 22-26 weeks for suspected GDM. Free hCG, PAPP-A and NT MoMs were compared amongst the group having an OGTT with confirmed GDM and those in which GDM was not confirmed. A second comparison group consisted of all non-aneuploidy singleton pregnancies in which no OGTT was performed. Results: During the three-year period, 27,660 singleton pregnancies were screened of which 7429 cases had an OGTT of which 870 cases were classed as GDM by WHO criteria. There was a significant 7-9% reduction in both PAPP-A and free hCG MoM in the GDM group compared with either the OGTT non-GDM group or the remaining pregnancies with no known risk factors for evidence of GDM. There was no difference in the NT measurements. Conclusions: First trimester concentrations of PAPP-A and free hCG are reduced in pregnancies that subsequently are diagnosed with GDM and may be useful in further screening algorithms for this disorder although the sensitivity alone is quite poor.

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First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death

Abstract: Objectives

Cited by 103 publications

References 33 publications

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Recommendations on prenatal screening and the connections to other diseases such as thyroid dysfunction

The association between gestational diabetes mellitus and first trimester aneuploidy screening markers

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