Maternal serum cytokines at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: The aim of this case-control study at 30-33 weeks, a few days or weeks before the clinical onset of preeclampsia (PE), was to assess whether serum concentrations of cytokines differ between patients who are destined to develop PE and those with uncomplicated pregnancies. METHODS: A panel of cytokines was measured using Luminex technology at 30-33 weeks' gestation in 39 cases that developed PE at or after 34 weeks and 117 unaffected controls. RESULTS: The serum concentrations of most analysed cytokines were no different in women who developed PE than in controls. The proportions of women with detectable concentrations of MIP-1α and IL-8 were significantly lower in those with PE than in the controls (MIP-1α: 14/39 vs 76/117, P = 0.003; IL-8:13/39 vs 83/117, P < 0.0001). The median maternal serum concentration of IL-1ß was significantly lower in the PE cases than in the controls (0.38 pg/mL, range 0.01-0.92, vs 0.60 pg/mL, range 0.02-3.54, P = 0.005). CONCLUSION: Our findings do not lend support to the hypothesis that systemic inflammation precedes the onset of PE or that cytokines are good markers for such inflammation and certainly the panel of cytokines we examined does not provide useful prediction of subsequent development of PE.

Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy.

BACKGROUND: The aim of this study is to validate the Fetal Medicine Foundation (FMF) multiple logistic regression algorithm for prediction of risk of pre-eclampsia in an Australian population. This model, which predicts risk using the population rate of pre-eclampsia, a variety of demographic factors, mean maternal arterial blood pressure (MAP), uterine artery PI (UtA PI) and pregnancy-associated plasma protein A (PAPP-A), has been shown to predict early-onset pre-eclampsia (delivery prior to 34 weeks) in 95% of women at a 10% false-positive rate. METHODS: All women who attended first trimester screening at the Royal Prince Alfred Hospital had their body mass index (BMI), MAP and UtA PI assessed in addition to factors traditionally used to assess aneuploidy (including PAPP-A MoM). After delivery, risks of early-onset (delivery prior to 34 weeks) pre-eclampsia, late pre-eclampsia and gestational hypertension were calculated using the FMF risk algorithm. RESULTS: A total of 3099 women were screened and delivered locally. 3066 (98.9%) women had all data to perform pre-eclampsia screening available. This included 3014 (98.3%) women with a live birth, where risks of early pre-eclampsia were calculated. Twelve women were delivered before 34 weeks because of early pre-eclampsia with a prevalence of early pre-eclampsia of 1 in 256 pregnancies. Risks generated through the use of maternal history, MAP, UtA PI and PAPP-A detected 41.7 and 91.7% of early pre-eclampsia at a false-positive rate of 5 and 10%, respectively. CONCLUSIONS: This study shows that the FMF early pre-eclampsia algorithm is effective in an Australian population.

Uterine artery Doppler at 30-33 weeks' gestation in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of measuring uterine artery pulsatility index (PI) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Screening study in singleton pregnancies at 30-33 weeks' gestation including 4,294 cases that were unaffected by PE, gestational hypertension (GH) or delivery of small for gestational age neonates (normal group), 145 that subsequently developed PE, with 37 cases requiring delivery at 34-37 weeks (intermediate-PE) and 108 delivering at or after 38 weeks (late-PE) and 161 that developed GH. The a priori risks for intermediate- and late-PE from maternal demographic characteristics and medical history were derived by logistic regression analysis. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for uterine artery PI, which were calculated from fitted bivariate gaussian distributions. RESULTS: In screening for PE by a combination of maternal characteristics and uterine artery PI, the estimated detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 70.3 and 54.6%, respectively. CONCLUSION: Combined testing by maternal characteristics and uterine artery PI at 30-33 weeks could effectively identify women at high risk for subsequent development of PE.

Maternal serum placental growth factor, pregnancy-associated plasma protein-a and free ß-human chorionic gonadotrophin at 30-33 weeks in the prediction of pre-eclampsia.

OBJECTIVE: To investigate the potential value of maternal serum concentrations of free ß-human chorionic gonadotrophin (ß-hCG), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 30-33 weeks of gestation in the prediction of pre-eclampsia (PE) developing at or after 34 weeks. METHODS: Serum free ß-hCG, PAPP-A and PlGF were measured at 11-13 and at 30-33 weeks of gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. The measured concentration of metabolites was converted into multiples of the unaffected median (MoM) and the MoM values in the PE and control groups were compared. RESULTS: At 11-13 weeks, serum PlGF and PAPP-A, but not free ß-hCG, were significantly lower in the PE group than in the controls (0.824, 0.748 and 0.857 vs. 1.000 MoM). At 30-33 weeks in the PE group, PlGF was reduced (0.356 MoM), free ß-hCG was increased (1.750 MoM), but PAPP-A was not significantly different (0.991 MoM) from control (1.000 MoM). In screening for PE at 30-33 weeks by a combination of maternal characteristics and serum PlGF, the estimated detection rates, at a false-positive rate of 10%, of intermediate PE (requiring delivery at 34-37 weeks) and late PE (with delivery after 37 weeks) were 85.7 and 52.8%, respectively. The performance of screening was not improved by the addition of free ß-hCG or the free ß-hCG/PlGF ratio. CONCLUSION: Screening by maternal characteristics and serum PlGF at 30-33 weeks could identify most pregnancies that will subsequently develop PE.

Combined screening for preeclampsia and small for gestational age at 11-13 weeks.

OBJECTIVE: To combine a specific algorithm for small for gestational age (SGA) without preeclampsia (PE) and another algorithm for PE in the prediction of SGA and PE. METHODS: This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.3%) that subsequently developed PE, 3,168 (5.1%) that delivered SGA neonates and 57,458 that were unaffected by PE and SGA. We developed a prediction algorithm for SGA requiring delivery before 37 weeks' gestation (preterm-SGA) from maternal characteristics, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A and placental growth factor multiple of the median values. We then examined the performance of this algorithm individually and in combination with a previously reported algorithm for early-PE in the prediction of SGA and PE. RESULTS: When screen positivity was defined by risk cutoff of 1:200 using the algorithm for early-PE and the risk cutoff of 1:150 using the algorithm for preterm-SGA, the false positive rate was 10.9% and the detection rates of early-PE, late-PE, preterm-SGA and term-SGA were 95.3, 45.6, 55.5 and 44.3%, respectively. CONCLUSIONS: Effective first-trimester screening for early-PE and preterm-SGA can be provided by the combined use of the specific algorithms.

Systolic, diastolic and mean arterial pressure at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of measuring mean arterial pressure (MAP), systolic (sBP) and diastolic (dBP) blood pressure at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Screening study in singleton pregnancies at 30-33 weeks' gestation including 4,294 that were unaffected by PE, gestational hypertension (GH) or delivery of small-for-gestational-age neonates (normal group), 145 that subsequently developed PE [37 cases requiring delivery at 34-37 weeks (intermediate PE) and 108 delivering at or after 38 weeks (late PE)] and 161 that developed GH. The a priori risks for intermediate and late PE from maternal demographic characteristics and medical history were determined. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for MAP, sBP and dBP, which were calculated from fitted bivariate gaussian distributions. RESULTS: The mean multiple of median MAP, sBP and dBP were significantly higher in the intermediate and late PE groups than in the normal group. In screening by a combination of maternal characteristics and MAP, the estimated detection rates of intermediate and late PE, at a false-positive rate of 10%, were 70.3 and 62.0%, respectively. The respective detection rates for sBP were 62.2 and 59.3% and for dBP were 62.2 and 57.4%. CONCLUSION: Combined testing by maternal characteristics and blood pressure at 30-33 weeks could effectively identify women at high risk for subsequent development of PE.

Maternal serum soluble endoglin at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of maternal serum concentration of soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Serum sEng was measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. Regression analysis was used to determine which of the factors amongst the maternal characteristics were significant predictors of first- and third-trimester log10 sEng in the control group. The measured values of sEng were converted into multiples of the unaffected median (MoM) and the MoM values in the PE and controls were compared. RESULTS: The median sEng MoM at 30-33 weeks was significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls (0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference between the groups. In screening by a combination of maternal characteristics and third-trimester sEng, the detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 64.3 and 50.0%, respectively. CONCLUSION: Screening by maternal characteristics and sEng at 30-33 weeks could identify most pregnancies that will subsequently develop PE.

Second-trimester screening for trisomy-21 using prefrontal space ratio.

OBJECTIVE: To investigate the potential value of prefrontal space ratio (PFSR) in second-trimester screening for trisomy-21. METHODS: A retrospective study utilizing stored midsagittal two-dimensional images of fetal profiles in 240 euploid and 45 trisomy-21 pregnancies at 16(+0)-23(+6) weeks' gestation. The vertical distance between the leading edge of the skull and that of the skin (D1) and the distance between the skull and the mandibulo-maxillary line (D2) were measured and the D1:D2 ratio (PFSR) was calculated. In euploid pregnancies, regression analysis was used to determine the association between D1, D2 and PFSR with gestational age (GA). D1 and D2 were expressed as delta (Δ) values with gestational age. ΔD1, ΔD2 and PFSR in cases and controls were compared. RESULTS: In trisomy-21, compared to controls, ΔD1 was increased (1.417 vs. 0.000 mm, p < 0.0001), ΔD2 was decreased (-0.842 vs. 0.000 mm, p = 0.003) and PFSR was increased (0.753 vs. 0.463, p < 0.0001). At a false-positive rate of 5%, the detection rates in screening by ΔD1, ΔD2 and PSFR were 80.0% (95% CI 65.4-90.4), 46.7% (95% CI 31.7-62.1) and 100.0% (95% CI 92.1-100.0), respectively. CONCLUSION: The PFSR is an effective marker in second-trimester screening for trisomy-21.

Second-trimester uterine artery Doppler in the prediction of stillbirths.

OBJECTIVE: To examine the role of second-trimester uterine artery Doppler in the prediction of stillbirths. METHODS: Uterine artery pulsatility index (PI) was measured at 20-24 weeks' gestation in 65,819 singleton pregnancies. The PI was converted to multiples of median (MoM) and compared in live births and stillbirths. Regression analysis was used to determine the significance of association between log(10) uterine artery PI MoM and gestational age (GA) at delivery in cases of stillbirths. RESULTS: There were 306 (0.46%) stillbirths and in 159 (52.0%) of these there was pre-eclampsia (PE), placental abruption and/or birthweight below the 10th percentile (small for gestational age, SGA). In the stillbirths, the uterine artery PI MoM was significantly higher than in live births and was inversely associated with GA at delivery. The uterine artery PI MoM was above the 90th percentile in 80.6% of stillbirths with PE, abruption and/or SGA delivering at <32 weeks' gestation, in 41.9% at 33-36 weeks and in 34.3% at ≥37 weeks, and the respective percentages for stillbirths without PE, abruption or SGA were 15.8, 25.0 and 12.4%. CONCLUSION: Second-trimester uterine artery PI is effective in identifying early stillbirths in association with PE, abruption or SGA but not late deaths in the absence of PE, abruption or SGA.

First-trimester screening for spontaneous preterm delivery with maternal characteristics and cervical length.

OBJECTIVE: It was the aim of this study to examine the potential value of cervical length at 11-13 weeks' gestation in the prediction of spontaneous preterm delivery. METHODS: This was a screening study for spontaneous preterm delivery in singleton pregnancies from cervical length measured by transvaginal ultrasound at 11-13 weeks' gestation. The performance of screening for preterm delivery by cervical length alone and with maternal characteristics was estimated. RESULTS: In the 9,974 pregnancies included in the study, spontaneous delivery before 34 weeks occurred in 104 (1.0%) cases. Multivariate regression analysis in the term delivery group demonstrated that for the log(10) cervical length, significant independent contributions were provided by fetal crown-rump length, maternal height, age, racial origin and parity. The median cervical length multiple of the median (MoM), corrected for maternal characteristics, was significantly lower in the preterm (0.892 MoM, 95% CI 0.829-0.945) than in the term delivery group (0.994 MoM, 95% CI 0.919-1.082; p < 0.0001). In screening by a combination of maternal characteristics and cervical length, the estimated detection rate of preterm delivery was 54.8% (95% CI 44.7-64.6), at a false-positive rate of 10%. CONCLUSIONS: Effective first-trimester screening for spontaneous early preterm delivery can be provided by a combination of maternal characteristics and cervical length.

A competing risks model in early screening for preeclampsia.

OBJECTIVE: It was the aim of this study to develop models for the prediction of preeclampsia (PE) based on maternal characteristics and biophysical markers at 11-13 weeks' gestation in which gestation at the time of delivery for PE is treated as a continuous variable. METHODS: This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.4%) cases that subsequently developed PE and 57,458 cases that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes' theorem was used to combine the prior information from maternal characteristics with the uterine artery pulsatility index (PI) and the mean arterial pressure (MAP), using multiple of the median values. RESULTS: The risk for PE increased with maternal age, weight, Afro-Caribbean and South Asian racial origin, previous pregnancy with PE, conception by in vitro fertilization and a medical history of chronic hypertension, type 2 diabetes mellitus as well as systemic lupus erythematosus or antiphospholipid syndrome. In pregnancies with PE, there was an inverse correlation between multiple of the median values of the uterine artery PI and MAP with gestational age at delivery. Screening by maternal characteristics, uterine artery PI and MAP detected 90% of PE cases requiring delivery before 34 weeks and 57% of all PE cases at a fixed false-positive rate of 10%. CONCLUSIONS: A new model has been developed for effective first-trimester screening for PE.

Birthweight with gestation and maternal characteristics in live births and stillbirths.

OBJECTIVE: To establish a normal range of birthweight with gestational age (GA) at delivery and examine the contribution of maternal characteristics in defining growth restriction in stillbirths. METHODS: In 69,895 normal singleton pregnancies, regression analysis was used to determine the association of birthweight with GA and maternal characteristics. The proportion of 290 stillbirths classified as small for GA depending on inclusion or exclusion of maternal characteristics was determined. RESULTS: In normal pregnancies, there was a polynomial association between birthweight and GA. Birthweight increased with maternal weight, height and parity and was lower in Africans and South Asians than in Caucasians. Birthweight for GA was reduced in antepartum stillbirths (n = 243; p < 0.0001) but not in intrapartum stillbirths (n = 47; p = 0.334). There was no significant difference in the proportion of antepartum stillbirths with birthweight below the 10th percentile when birthweight was corrected for GA only compared to correction for GA and maternal characteristics (53.1 vs. 54.3%). The birthweight was below the 10th percentile in 71.8% of antepartum stillbirths at <32 weeks' gestation, in 47.2% at 33-36 weeks and in 31.5% at ≥37 weeks. CONCLUSION: Correction of birthweight for maternal characteristics does not alter the proportion of stillbirths that are small for GA.

Reference range of birth weight with gestation and first-trimester prediction of small-for-gestation neonates.

OBJECTIVE: Firstly, to establish a reference range of birth weight with gestation at delivery; secondly, to identify maternal characteristics that are significantly associated with birth weight; and thirdly, to determine if combinations of maternal characteristics, fetal nuchal translucency thickness (NT), and serum concentrations of free beta-human chorionic gonadotrophin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are significant predictors of small-for-gestational-age (SGA) neonates in the absence of preeclampsia. METHOD: Maternal characteristics were recorded; fetal NT, maternal serum free ß-hCG and PAPP-A were measured at 11 weeks to 13 weeks 6 days in 33,602 women with singleton pregnancies. Regression analysis was used to determine the association of birth weight with gestation at delivery and to establish a reference range with gestation. Logistic regression analysis was used to determine if maternal factors, fetal NT, free ß-hCG, and PAPP-A contribute significantly in predicting SGA in the absence of preeclampsia. RESULTS: Birth weight increased with maternal weight and height; it was higher in parous than in nulliparous women and in those with a medical history of pre-pregnancy diabetes mellitus, and it was lower in cigarette smokers, in all racial groups other than in Caucasian women, and in those with a medical history of chronic hypertension and in those who previously delivered SGA neonates. In the SGA group compared with the unaffected group, there were lower median delta NT (0.10 vs 0.12 mm), free ß-hCG [0.9 vs 1.0 MoM (multiples of median)], and PAPP-A (0.8 vs 1.0 MoM). The prediction of SGA provided by maternal factors was significantly improved by the addition of fetal NT and PAPP-A (34.0 vs 37.0% at a false-positive rate of 10%). CONCLUSION: Prediction of the birth of SGA neonates in the absence of preeclampsia can be provided in the first trimester of pregnancy by a combination of maternal characteristics and measurements of parameters used in early screening for aneuploidies.

First-trimester prediction of macrosomia.

OBJECTIVE: To determine if combinations of maternal characteristics and measurements of parameters used in screening for aneuploidies at 11-13 weeks provide significant prediction of macrosomia. METHOD: Maternal characteristics, fetal nuchal translucency (NT), free ß-human chorionic gonadotrophin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were recorded at 11(+0)-13(+6) weeks in 36,743 singleton pregnancies. Regression analysis was used to determine if in predicting macrosomia significant contributions are provided by maternal factors, fetal NT, free ß-hCG and PAPP-A. RESULTS: The risk for macrosomia increased with maternal weight and height and was higher in parous women with previous delivery of a macrosomic baby and in those with diabetes mellitus; the risk was lower in women of African and South Asian racial origins, in cigarette smokers and in those with chronic hypertension. In the macrosomic group compared to the unaffected group there were higher Δ-NT (0.167 vs. 0.116 mm), free ß-hCG (1.010 vs. 0.964 MoM) and PAPP-A (1.103 vs. 1.003 MoM). Prediction of macrosomia provided by maternal factors was significantly improved by fetal NT, free ß-hCG and PAPP-A (34.4 vs. 33.1% at a false-positive rate of 10%). CONCLUSION: Prediction of macrosomia is provided in the first trimester of pregnancy by a combination of maternal characteristics and measurements of parameters used in screening for aneuploidies.

Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP-A at 11-13 weeks.

OBJECTIVE: To explore if the addition of pregnancy-associated plasma protein-A (PAPP-A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease. METHODS: Prospective screening study for early preeclampsia (PE), late PE and gestational hypertension (GH) in women attending their first hospital visit at 11(+0)-13(+6) weeks of gestation. The performance of screening for PE and GH by combinations of maternal factors, uterine artery with the lowest pulsatility index (L-PI), mean arterial pressure (MAP) and serum PAPP-A was determined. RESULTS: There were 8061 unaffected controls, 37 of whom developed early PE, 128 with late PE and 140 with GH. Compared to the controls, in early PE and late PE MAP and uterine artery L-PI were increased and PAPP-A was decreased. In GH PAPP-A was not significantly different from controls. In screening for a combination of maternal factors, uterine artery L-PI, MAP and PAPP-A the detection rate of early PE was 83.8%, at a 5% false-positive rate. In the prediction of late PE and GH there was no significant improvement from the addition of PAPP-A to the combination of maternal factors, MAP and uterine artery L-PI. CONCLUSION: Measurement of PAPP-A improves the performance of screening for early PE provided by a combination of maternal factors and biophysical tests at 11-13 weeks.

Normal ranges of embryonic length, embryonic heart rate, gestational sac diameter and yolk sac diameter at 6-10 weeks.

OBJECTIVES: To construct normal ranges for embryonic crown-rump length (CRL), heart rate (HR), gestational sac diameter (GSD) and yolk sac diameter (YSD) at 6-10 weeks of gestation. METHODS: We examined 4,698 singleton pregnancies with ultrasound measurements of CRL, HR, GSD and YSD at 6-10 weeks and CRL at 11-13 weeks resulting in the live birth after 36 weeks of phenotypically normal neonates with birth weight above the 5th centile. Gestational age was derived from CRL at the 11- to 13-week scan using the formula of Robinson and Fleming. Regression analysis was used to establish normal ranges of CRL, fetal HR, GSD and YSD with gestation, and fetal HR, GSD and YSD with CRL. RESULTS: At 6-10 weeks there were significant quadratic associations between CRL, GSD, YSD and gestation and between HR, GSD, YSD and CRL, and a cubic association between HR and gestation. The estimated gestation from CRL was the same as that of Robinson and Fleming for a CRL of 10.2-36.5 mm, but the formula of Robinson and Fleming underestimated the gestation by 1 day for a CRL 7.4-10.2 mm and this increased to 9 days for a CRL of 1 mm. CONCLUSION: This study established normal ranges for early pregnancy biometry.

Maternal serum ADAM12 (A disintegrin and metalloprotease) in chromosomally abnormal pregnancy at 11-13 weeks.

OBJECTIVE: The objective of this study was to investigate the potential value of ADAM12 (A disintegrin and metalloprotease) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities. STUDY DESIGN: The concentration of ADAM12 was measured at 11-13 weeks in cases of trisomy 21 (n = 49), trisomy 18 (n = 28), trisomy 13 (n = 20), Turner syndrome (n = 29), triploidy (n = 10), and euploid pregnancies (n = 272). The levels of ADAM12, expressed as multiples of median (MoM), were compared in cases and controls and were assessed for association with free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A). RESULTS: The median ADAM12 value in trisomy 21 (0.961 MoM) was not significantly different from the euploid fetuses (1.013 MoM), but in trisomy 18 (0.697 MoM), trisomy 13 (0.577 MoM), triploidy (0.426 MoM), and Turner syndrome (0.747 MoM), the levels were significantly lower. In both the euploid and aneuploid pregnancies, there was a significant association between ADAM12 and free beta-hCG and PAPP-A. CONCLUSION: Maternal serum ADAM12 concentration at 11-13 weeks of gestation is unlikely to be useful in first-trimester screening for chromosomal abnormalities because in trisomy 21 the levels are not significantly different from normal, and in the other chromosomal defects, there is a significant association between ADAM12 and the traditional biochemical markers of free beta-hCG and PAPP-A.

First-trimester maternal serum matrix metalloproteinase-9 (MMP-9) and adverse pregnancy outcome.

OBJECTIVE: To investigate the potential value of maternal serum matrix metalloproteinase-9 (MMP-9) in first-trimester screening for preeclampsia and spontaneous early preterm delivery. METHODS: The concentrations of MMP-9, tumour necrosis factor soluble receptor-1 (TNF-R1), pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UA-PI) were measured at 11(+0) - 13(+6) weeks in cases of preeclampsia (n = 128), gestational hypertension (n = 88), small for gestational age (n = 296), spontaneous early preterm delivery (n = 57) and controls (n = 569). The distributions of measured metabolites and UA-PI in the control and adverse outcome groups were compared. Logistic regression analysis was used to determine the significant contributors in the prediction of adverse outcomes. RESULTS: The median MMP-9 was higher than controls in the preeclampsia (1.190 MoM) and preterm delivery (1.187 MoM) groups. In the preeclampsia group there was a significant association between serum MMP-9 and TNF-R1 (r = 0.523, P < 0.0001). Significant prediction of preeclampsia was provided by history and UA-PI, and prediction of preterm delivery was provided by history and neither was improved by the addition of MMP-9. CONCLUSION: In pregnancies developing preeclampsia, the increased level of MMP-9 and the good correlation with TNF-R1 suggest the presence of an underlying inflammatory process. In the pregnancies resulting in spontaneous preterm delivery the small increase in MMP-9 is not useful in the prediction of preterm delivery.

First-trimester maternal serum a disintegrin and metalloprotease 12 (ADAM12) and adverse pregnancy outcome.

OBJECTIVE: To examine the possible association of maternal serum a disintegrin and metalloprotease (ADAM12) in the first trimester of pregnancy and subsequent development of preeclampsia, delivery of small for gestational age (SGA) neonates, and spontaneous preterm delivery. METHODS: The maternal serum concentration of ADAM12 at 11 0/7 to 13 6/7 weeks was measured in 128 cases of preeclampsia, 88 cases of gestational hypertension, 296 cases with SGA neonates, 58 cases of spontaneous preterm delivery, and 570 controls. Regression analysis was used to determine which of the maternal factors and fetal crown rump length were significant predictors of ADAM12 in the control group, and from the regression model the value in each case and control was expressed as a multiple of median (MoM). The levels of ADAM12 MoM were compared in cases and controls. RESULTS: In the control group the concentration of ADAM12 increased with fetal crown rump length, decreased with maternal weight and was higher in African-American than in white women. There was a significant association between ADAM12 and pregnancy-associated plasma protein A (r=0.417, P<.001) and between each metabolite and birth weight percentile (r=0.176, P<.001 and r=0.109, P=.009). In the SGA group, the median ADAM12 concentration (0.848 MoM) was lower (P<.001), but in pregnancies complicated by preeclampsia (0.954 MoM), gestational hypertension (1.013 MoM), and spontaneous preterm delivery (1.048 MoM) the levels were not significantly different from controls (1.011 MoM). CONCLUSION: There is a good correlation between the maternal serum ADAM12 and pregnancy-associated plasma protein A concentration. Measurement of ADAM12 does not provide useful prediction of SGA, preeclampsia, or spontaneous preterm delivery. LEVEL OF EVIDENCE: II.

Management of hypertriglyceridaemia-induced acute pancreatitis in pregnancy.

INTRODUCTION: Acute pancreatitis is a recognised rare complication in pregnancy. The reported incidence varies between 3 and 7 in 10 000 pregnancies and is higher in the third trimester. The commonest causes in pregnancy include gallstones, alcohol and hypertriglyceridaemia. Non-gallstone pancreatitis is associated with more complications and poorer outcome with hypertriglyceridaemia-induced acute pancreatitis having mortality rates ranging from 7.5 to 9.0% and 10.0 to 17.5% for mother and foetus, respectively. CASE HISTORY: A 40-year-old para 4 woman, who presented at 15(+4) weeks' gestation, was diagnosed with acute pancreatitis. Past medical history included Graves' disease and hypertriglyceridaemia. Fenofibrate was discontinued immediately after discovery of the pregnancy. Initial investigations showed elevated amylase (475.0 µ/L) and triglycerides (46.6 mmol/L). Imaging revealed an inflamed pancreas without evidence of biliary obstruction/gallstones hence confirming the diagnosis of hypertriglyceridaemia-induced acute pancreatitis. Laboratory tests gradually improved (triglyceride 5.2 mmol/L on day 17). On day 18, ultrasound confirmed foetal demise (18(+1) weeks) and a hysterotomy was performed as she had had four previous caesarean sections. CONCLUSION: Management of acute pancreatitis in pregnancy requires a multi-disciplinary approach. Hypertriglyceridaemia-induced acute pancreatitis has poor outcomes when diagnosed in early pregnancy. Identifying those at risk pre-pregnancy and antenatally can allow close monitoring through pregnancy to optimise care.