Hi, my name is Yul, and along with my group member, Geraldine, who will be presenting to you today, the risk of placental dysfunction disorders after prior miscarriages: a population-based study. Our presentation is based on this paper published in July 2014 in the American Journal of Obstetrics and Gynecology. This is the outline. So the objective of this paper was to study the association between prior miscarriages and risks of placental dysfunction disorders, including small for gestational age, spontaneous preterm labor, placental abruption, preeclampsia, and stillbirths. This was a retrospective population-based cohort study. And the population was obtained from the Swedish medical birth register containing 98% of all births in Sweden. This is comprised of primiparous women from 1995 to 2009 with over 600,000 records divided into four groups– no prior miscarriages as a reference group, the second group being one miscarriage, the third group being two miscarriages, and the fourth group being three or more miscarriages. Preeclampsia, stillbirth, and small for gestational age, as well as placental abruption were further categorized into preterm or births before 37 weeks of gestation and term births at 37 weeks of gestation or later. Preterm labor was further categorized into very preterm births, or births before 32 weeks of gestation, and moderately preterm births, which are births between 32 and 36 weeks of gestation. The risk was subsequently calculated at odds ratios and 95% confidence intervals. The following for covariables were controlled for by the study. And these included maternal age, height in BMI in early pregnancy, country at birth, smoking, education, IVF, chronic hypertension, pregestational diabetes, hypothyroidism, SLE, fetal sex, and the year of childbirth. On to the results, for preeclampsia, the authors found that women with one or two prior miscarriages had no significant increase in the risk of preeclampsia. However, women with three or more prior miscarriages had significantly higher risk of preeclampsia in preterm babies, as seen in the table above. For still births, women with one or two prior miscarriages had no significant increase in the risk of still births. Women with three or more prior miscarriages had significantly higher risk of stillbirth in preterm babies. With regards to placental abruption, women with one prior miscarriage had no significant increase in risk of placental abruption. However, women with two and three or more prior miscarriages had significantly higher risk of placental abruption in preterm babies. With regards to small for gestational age, women with one prior miscarriage had no significant increase in risk of SGA. However, women with two and three or more prior miscarriages had significantly higher risk of SGA in preterm babies. Preterm labor was a different story. In preterm labor, women with 1, 2, and 3 or more prior miscarriages all showed significantly higher risk of spontaneous preterm labor, especially in very preterm births. Interestingly, the risk also showed a dose response pattern with increasing numbers of prior miscarriages correlating to increased risks. In summary, there is an increased risk of placental dysfunction in women with previous miscarriages. This is especially true for women with three or more prior miscarriages. Also women with any history of miscarriage had increased risk for preterm labor. And these risks were significantly increased only in preterm births. My name is Geraldine and I will be continuing with the discussion of the strengths and limitations of this paper, looking at other literature to see if the support of findings discussed in this paper earlier and the implications of this paper. Some of the strengths of this paper include the use of a very large study population. As mentioned earlier, the total number of subjects numbered more than 600,000, which gave the authors of the study the ability to study rare events in detail. Another strength is a population-based design. This is a nationwide study, which means that the results may be applicable to other settings. Also, important confounders will controlled for. Some of the limitations of these paper include the presence of other confounders which cannot be controlled for, such as the existence of trombofilia and polycystic ovarian syndrome in the subjects. Also, after statistical analysis, some of the sample sizes of interest were actually quite small. The documentation of miscarriages in this people was also a problem. As it was self-reported and therefore there is no information of underlying etiology or the gestational length at the miscarriage. There was also a lack of data on previous abortions in the subject. This is significant because recent studies have linked increased risk of placental abruption and low birth weight to previous abortions. This study shows an association between previous miscarriages and a risk of placental dysfunction, especially with the regards for small for gestational age and preterm labor. Now, we will review some of the recent literature regarding these two conditions. In an earlier study done in 2008 by Bhattacharya, which was a population-based retrospective cohort study done in Scotland comparing women with 1 previous miscarriage and women with no previous miscarriage. And it showed that in women with one previous miscarriage, there were higher rates of preterm labor and low birth weight in this current pregnancy. In a study done in 2011 by Weintraub, also a population-based retrospective cohort study, but in Israel, comparing women with one previous miscarriage and women with no previous miscarriages, also showed a higher rate of IUGR and preterm labor in women with a previous miscarriage. A study done by Basso in 1998, a population-based retrospective cohort study done in Denmark comparing women with one or more previous miscarriage and women with no previous miscarriages also showed a higher rate of preterm labor and low birth weight in mothers with a previous miscarriage. This paper also demonstrate that there was an increased rate of preterm labor in women with previous miscarriages. In other words, women with one or more previous miscarriages actually had higher risk for preterm labor. In a study done by Jivraj in 2001, a retrospective cohort study with data taken from a single tertiary institution in the United Kingdom compared women with recurrent miscarriages, defined as 3 or more consecutive miscarriages, and women without previous miscarriages, also showed a higher rate of SGA preterm labor in patients with recurring miscarriages. Theorists also have shown consistent results that previous miscarriages carry with them increased risk of preterm labor, small for gestational age, and low birth weight in a current pregnancy. The results for preterm labor in mothers with previous miscarriages was especially significant. Also, there’s a dose-response relationship observed between a number of previous miscarriages and a development of subsequent preterm labor. Some studies carried out support the hypothesis that miscarriage and placental dysfunction have a common pathogenesis of early placentation failure. An increase in VEGF or vascular endothelial growth factor is associated with miscarriage and placental dysfunction disorders. There’s an increase in angiogenesis and a premature onset of maternal circulation as a result of VEGF, and this increases the oxidative stress. Also, placental dysfunction disorders have risk of recurrence and may predispose to each other. Fetal genotype may also affect the viability of pregnancy in a mother prone to placentation failure. In a fetal genotype susceptible to implantation failure, it is likely that a pregnancy will result in complete failure of early placentation and miscarriage. In a fetal genotype that is not prone to implantation failure, it is likely that a pregnancy will be viable. However, with the possible risk of late placentation dysfunction disorder later in the pregnancy. The results from this paper suggest that there should be greater emphasis on accurate documentation of previous miscarriages. Women with a history of two or more miscarriages may be considered a high risk pregnancy. Which means that they should be seen more frequently by [INAUDIBLE] specialized multi-disciplinary team. Also, there should be further research on possible prophylactic treatment in women with previous and recurring miscarriages so as to better increase their chances of carrying the common pregnancy to term. These are some of the references. Thank you.