Neonatal Outcomes.

<p>Data is shown as number (%) and mean (± standard error of the mean) where appropriate. Where IUGR = intrauterine growth restriction, NEC = nectrotising enterocolitis, IVH = intraventricular haemorrhage, RDS = respiratory distress syndrome.</p

Pre-eclamptic characteristics.

<p>Data is shown as number (%) and mean (± standard error of the mean) where appropriate. Where SBP = systolic blood pressure, DBP = diastolic blood pressure, ALT = alanine transferase.</p

Baseline Characteristics of women with pre-eclampsia with or without fetal growth restriction.

<p>Data is shown as number (%) and mean (± standard error of the mean) where appropriate. Where FGR = fetal growth restriction, BMI = body mass index.</p

ADAM12 levels in sera collected from women at first presentation with a PUL, categorised according to final pregnancy outcome.

<p>Definite ectopic pregnancy (dEP: n = 17), probable ectopic pregnancy (pEP: n = 8), definite viable intrauterine pregnancy (dVIUP: n = 28), definite nonviable intrauterine pregnancy (dNVIUP: n = 26), spontaneously resolving PUL (srPUL: n = 27), treated persistent PUL (tpPUL: n = 3) and not pregnant (NP: n = 11). A ROC curve was generated (‘ROC of ADAM12’) to compare serum ADAM12 concentrations in patients with a dEP versus all other outcomes. The analysis was repeated (‘ROC of ADAM12 -PUL Data’) after ‘ambiguous’ pregnancy outcomes (srPUL, tpPUL and pEP) were excluded.</p

Patient recruitment: 120 patients with an initial diagnosis of a PUL were recruited to the study and grouped according to final pregnancy outcomes.

<p>Patient recruitment: 120 patients with an initial diagnosis of a PUL were recruited to the study and grouped according to final pregnancy outcomes.</p

MMP-15 is localised to the syncytiotrophoblast and up-regulated in preeclamptic placenta.

<p>Representative immunohistochemistry for endoglin (<b>A, B</b>) and MMP-15 (<b>D, E</b>), shows both proteins localize to the syncytiotrophoblast in pre-eclamptic (<b>A, D</b>) and pre-term control (<b>B, E</b>) placentas. Immunohistochemistry on serial sections (2 µm) of placenta revealed co-localisation of endoglin (<b>G</b>) and MMP-15 (<b>H</b>) to the syncytiotrophoblast. No staining was observed in isotype controls (<b>C, F</b>). Densitometric analysis of western blots for MMP-15 (<b>I, J</b>) revealed a significant increase in preeclamptic placentas (n = 8) compared to pre-term controls (n = 8). *p≤0.05.</p

MMP-15 inhibtion does not decrease soluble endoglin production <i>in vitro</i>.

<p>Treatment of HUVEC cells (<b>A)</b> and syncytialised BeWo cells (<b>B</b>) with MMP-14 siRNA alone or in combination with MMP-15 siRNA induced a significant decline in sEng production compared to scrambled siRNA, whilst MMP-15 siRNA alone had no effect. Data shown as mean±SEM, n = 3 experiments, *p≤0.05.</p

Clinical Characteristics of the preeclamptic cohort.

<p>Shown are clinical details of the two cohorts from whom we obtained placentas for our analyses. The preeclamptic cohort all had severe preeclampsia necessitating delivery preterm. Preterm controls where those who were delivered early for other indications but did not have preeclampsia. **p<0.001. SEM =  standard error of the mean, SBP =  systolic blood pressure, DBP =  diastolic blood pressure, BMI =  body mass index and GA =  gestational age.</p

Participant categorisation and baseline characteristics according to final pregnancy outcome (median ± SEM).

<p>Participant categorisation and baseline characteristics according to final pregnancy outcome (median ± SEM).</p

Doppler assessments performed at 36 weeks according to change in weight centile.

<p>MCA-PI according to weight centile change between the ultrasound performed at 28 weeks and 36 weeks (2a) MCA-PI according to weight centile change between the ultrasound performed at 28 weeks and birth (2b). CPR according to weight centile change between the ultrasound performed at 28 weeks and 36 weeks (2c) CPR according to weight centile change between the ultrasound performed at 28 weeks and birth (2d); UA-PI according to weight centile change between the ultrasound performed at 28 weeks and 36 weeks (2e) UA-PI according to weight centile change between the ultrasound performed at 28 weeks and birth (2f). * 5^th, 50^th and 95^th centile for Middle Cerebral Artery Pulsatility Index and Cerebroplacental Ratio at 36 weeks gestation (12); ** 5^th, 50^th and 95^th centile for Umbilical Artery Pulsatility Index at 36 weeks gestation (13).</p