Intraamniotic infection (IAI) during labor is a risk factor for postpartum endometritis. Current practice guidelines for IAI support a single dose of prophylactic antibiotics in the postpartum period following cesarean but not vaginal deliveries. This study aimed to determine whether a standardized risk-based strategy of extended antibiotic prophylaxis was associated with a reduced rate of endometritis.

BACKGROUND:Fetomaternal hemorrhage is associated with severe fetal morbidity and mortality. The recurrence risk of fetomaternal hemorrhage is unknown.OBJECTIVE:We sought to establish the recurrence rate of fetomaternal hemorrhage in a large integrated healthcare system over a 10-year period.STUDY DESIGN:In this retrospective study within the Kaiser Permanente Northern California medical system, cases of fetomaternal hemorrhage were defined by either an elevated fetal hemoglobin level as determined by flow cytometry for a concerning pregnancy outcome (preterm delivery, perinatal demise, neonatal anemia, or transfusion within the first 2 days of life) or by perinatal demise with autopsy findings suggestive of fetomaternal hemorrhage. The outcomes of subsequent pregnancies were reviewed for features of recurrence.RESULTS:Within the 2008 to 2018 birth cohort of 375,864 pregnancies, flow cytometry testing for fetal hemoglobin levels was performed in 20,582 pregnancies. We identified 340 cases of fetomaternal hemorrhage (approximately 1 in 1100 births). Within the cohort of 340 affected pregnancies, perinatal loss was recorded for 80 (23.5%) pregnancies and 50 (14.7%) pregnancies delivered neonates who required transfusion. The affected patients had 225 subsequent pregnancies of which 210 were included in the analysis. Of these, 174 (82.9%) advanced beyond the threshold of viability and were delivered within our healthcare system. There was 1 case of recurrent fetomaternal hemorrhage identified. The recurrent case involved a spontaneous preterm delivery of an infant who was noted to have an elevated reticulocyte count but was clinically well.CONCLUSION:Within our large integrated healthcare system, approximately 1 in 1100 pregnancies was affected by fetomaternal hemorrhage within a 10-year period, which is comparable with previous studies. We identified 1 case of recurrence, yielding a recurrence rate of 0.5%. This infant did not have features of clinically important fetomaternal hemorrhage. This information can inform counseling of patients with affected pregnancies.

INTRODUCTION: Fetomaternal hemorrhage (FMH) is an obstetric complication associated with adverse fetal and neonatal outcomes. Few reliable risk factors other than maternal trauma have been identified. Previous research has suggested an association between potentially obstructive umbilical cord abnormalities and FMH. METHODS: We conducted an IRB-approved case-control study within Kaiser Permanente Northern California between January 2008 and December 2017 to investigate whether cord abnormalities were associated with FMH. Cases were defined by adverse fetal or neonatal outcomes related to hypovolemia in the setting of a positive maternal flow cytometry for fetal hemoglobin. Controls were selected based on a negative flow result at time of delivery and available placental pathology report for review, matched to gestational age and year of delivery of cases. Delivery records and pathology reports were analyzed for 56 cases and 132 controls. RESULTS: There was at least one cord abnormality for 23.2% of cases and 25.8% of controls (P=.71). There were no significant differences between the two groups in placental weight percentile, cord length, or cord diameter. Marginal and velamentous cord insertion occurred slightly more frequently in controls compared to cases. Cord hypercoiling was found in 7.1% of cases vs 5.3% of controls (P=.74). CONCLUSION: We did not identify gross placental or cord characteristics associated with FMH. However, case numbers were too small for statistical significance and our study was limited to placentas sent to pathology, which may have biased our control group towards cord lesions. Further research is required to identify whether an association exists between cord abnormalities and FMH.

INTRODUCTION: Fetomaternal hemorrhage (FMH) and placental abruption may both result in adverse fetal and neonatal outcomes but have differing pathophysiology. Abruption reportedly can lead to small volume FMH, but a positive test for FMH does not indicate a diagnosis of abruption. METHODS: We performed a case-control study within Kaiser Northern California (2008–2017), first identifying all cases of FMH within this time period (defined as a positive flow cytometry for fetal hemoglobin and adverse fetal or neonatal outcomes related to hypovolemia). Cases of FMH were compared to matched controls from the same delivery cohort. We reviewed delivery records and placental pathology reports to identify whether placental abruption was clinically suspected. RESULTS: Our study included 56 women in the FMH group and 132 in the control group. Concern for placental abruption was noted in 10.6% of those without FMH and in 12.5% of those with FMH, with no significant difference between the two groups (P=.71). The adjusted odds ratio was 1.33 (95% CI .49–3.62) after adjusting for maternal age and maternal race/ethnicity. CONCLUSION: Placental abruption is not more likely to occur in clinically significant FMH compared to other deliveries for which placental pathology is obtained. Obstetric providers should consider FMH and abruption as separate clinical entities. Flow cytometry for fetal hemoglobin should be ordered in the setting of clinical suspicion for FMH, unexplained intrauterine fetal death, or adverse outcomes related to fetal or neonatal hypovolemia. The Kleihauer-Betke and flow cytometry tests for fetal hemoglobin do not confirm or refute the possibility of abruption.

INTRODUCTION: Clinically significant fetomaternal hemorrhage (CS-FMH) occurs in 1/1000-1/5000 pregnancies and has an unknown risk of recurrence. We sought to establish recurrence rate by analyzing reproductive histories of patients with CS-FMH confirmed by flow cytometry in a large integrated health care system over a 10-year period (375,864 total births). METHODS: We conducted an IRB-approved retrospective case series of patients with a positive flow result (>0.1% fetal red cells in maternal circulation) from January 2008 through May 2018 within Kaiser Permanente Northern California (KPNC). For cases of CS-FMH we collected indication for testing, adverse outcomes, reproductive history and demographics. RESULTS: Of over 19,000 patients tested, 1105 had a positive flow result. Of these, 7.4% had a result > 1.0%, with 85.4% of these identified as CS-FMH. Of CS-FMH cases, 28.6% had a fetal demise, 71.4% had a symptomatic neonate, and 4.3% had a neonatal demise. 58.6% presented with decreased fetal movement. Excluding cases of fetal demise, 90.0% had an abnormal fetal heart rate tracing (14.0% sinusoidal). Autopsy supported CS-FMH in all but one case of demise. There were no predictive demographic characteristics for CS-FMH. There were no cases of recurrent CS-FMH. Collectively, affected patients had 126 additional pregnancies with 75 liveborns. At term, a flow result ≥4.0% had a positive predictive value (PPV) of 100% for CS-FMH. For preterm deliveries, a result ≥ 1.0% had a PPV of 100%. CONCLUSION: The incidence of CS-FMH in our diverse KPNC population is 0.19/1000. We did not find an increased risk of recurrence in future pregnancies.

OBJECTIVES:Neonatal adiposity is associated with chronic metabolic sequelae such as diabetes and obesity. Identifying fetuses at risk for excess neonatal body fat may lead to research aimed at limiting nutritional excess in the prenatal period. We sought to determine whether fetal arm and leg soft tissue measurements at 28 weeks' gestation were predictive of neonatal percent body fat METHODS : In this prospective observational cohort study of singleton term pregnancies, we performed sonography at 28 and 36 weeks' gestation, including soft tissue measurements of the fetal arm and thigh (fractional limb volume and cross-sectional area). We estimated the neonatal body composition (percent body fat) using anthropometric measurements and air displacement plethysmography. We estimated Spearman correlations between sonographic findings and percent body fat and performed modeling to predict neonatal percent body fat using maternal characteristics and sonographic findings. RESULTS:Our analysis of 44 women yielded a mean maternal age of 30 years, body mass index of 26 kg/m(2), and birth weight of 3382 g. Mean neonatal percent body fat was 8.1% by skin folds at birth and 12.2% by air displacement plethysmography 2 weeks after birth. Fractional thigh volume measurements at 28 weeks yielded the most accurate model for predicting neonatal percent body fat (R(2) = 0.697; P = .001), outperforming models that used abdominal circumference (R(2)= 0.516) and estimated fetal weight (R(2)= 0.489). CONCLUSIONS:Soft tissue measurements of the fetal thigh at 28 weeks correlated better with neonatal percent body fat than currently used sonographic measurements. After validation in a larger cohort, our models may be useful for prenatal intervention strategies aimed at the prevention of excess fetal fat accretion and, potentially, optimization of long-term metabolic health.

To determine the effectiveness of 17 Alpha-Hydroxyprogesterone (17 OHP) in prevention of preterm birth in overweight and obese women with twin pregnancies. 17 OHP is known to decrease the frequency of preterm birth in singleton pregnancies with a history of preterm birth, but has not been shown to alter outcomes in twin pregnancies. We hypothesized that 17 OHP may be effective for a subset of twin pregnancies when stratified by weight and body mass index (BMI). This is a secondary analysis of the NICHD MFMU Network's "Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Multifetal Gestation" (STTARS twins). Women with fetal anomalies were excluded. Women were stratified by weight and by BMI. Rates of preterm birth less than 35 weeks were compared in each stratum for those receiving 17 OHP versus those receiving placebo. We identified 1286 women with twin pregnancies who met inclusion criteria; 670 (52%) had BMI ≥ 25, 362 (28%) BMI ≥30, 173 (13%) BMI ≥ 35, and 61 (4.7%) BMI ≥ 40. Overall, the mean gestational age of delivery was earlier for obese women (BMI≥30) compared to non-obese women (34.3 vs 34.9 weeks, p=0.005) on 17 OHP or placebo. For women with BMI > 30, 47% (84/176) of women receiving 17 OHP delivered before 35 weeks compared to 58% (68/184) of women receiving placebo (p=0.039). Non-obese women did not have a significant difference in preterm birth on 17 OHP compared to placebo (38% vs. 37%, p=0.81). While the overall rate of preterm birth was higher in obese patients with twins, treatment with 17 OHP appears to decrease the rate of preterm delivery in the setting of obese patients with a twin pregnancy. These findings may support a new indication for 17 OHP.

Treatment with 17 Alpha-Hydroxyprogesterone (17 OHP) has been shown to reduce the risk of preterm birth in women with a previous preterm delivery, however it is not known whether 17 OHP remains effective for women with higher body mass indices (BMI). The purpose of this study was to assess the effect of 17 OHP in women of varying BMIs. This is a secondary analysis of a multicenter, randomized, placebo-controlled trial of 17 OHP for the prevention of preterm birth among women with a prior spontaneous preterm birth. For this analysis, women randomized to receive 17 OHP were identified, and stratified into dichotomous BMI categories at varying cut-offs (25, 30, 35, 40). The primary outcome was spontaneous preterm birth prior to 37 weeks. The rate of spontaneous preterm birth was compared at each of these cut-offs. A similar analysis was performed using an outcome of preterm birth prior to 37 weeks, including indicated deliveries. There were 291 women meeting inclusion criteria: 133 (46%) had BMI > 25, 75 (26%) had BMI >30, 34 (12%) had BMI > 35, 12 (4%) had BMI > 40. Among these women receiving 17 OHP, there was no significant difference in the rate of spontaneous preterm birth when stratified by BMI. The preterm birth rate was 30% for BMI ≤ 25 versus 29% for BMI > 25 (p = 0.74), 30% versus 28% for BMI ≤30 versus > 30 (p=0.73), 31% versus 18% for BMI ≤35 versus > 35 (p=0.11), and 30% versus 17% for BMI ≤40 versus > 40 (p=0.32). Lower rates of spontaneous preterm birth were observed for obese and morbidly obese women, although the difference was not significant. When preterm birth from all causes was included, there remained no significant difference in the rate of preterm birth when analyzed by BMI. In this cohort of women with a prior spontaneous preterm birth receiving 17 OHP, increasing body mass index did not attenuate the effect of 17 OHP. This data supports the current practice of universal dosing of 17 OHP regardless of weight.

OBJECTIVE: To determine if residency training in the use of forceps and vacuums in vaginal deliveries is associated with their use in postgraduate practice.STUDY DESIGN: We surveyed all Ob/Gyn residency graduates of 4 academic programs from 2004-2012. The average number of vacuums and forceps performed per graduating resident was linked to respondents, who were then grouped by self report as using forceps alone, vacuums alone, or both in practice. Multivariable logistic regression determined predictors of use of forceps and vacuums in practice.RESULTS: The response rate was 61.2% (n=200). Those practicing obstetrics (n=171) were classified as forceps only (24%), vacuums only (22%), or both (54%). Use of forceps in practice was greater for those who graduated within the last 5 years (OR 7.55, 95% CI 2.37-24.07), felt inadequately trained in vacuums (OR 4.58, 95% CI 1.23-17.00), cared for a patient population <50% privately insured (OR 4.08, 95% CI 1.58-10.52), and performed more forceps in residency (OR 1.69, 95% CI 1.31-2.18 per 5 forceps performed on average). The only significant predictor of vacuum use was the number of vacuum deliveries performed in residency (OR 3.71, 95% CI 2.28-6.01 per 5 vacuums performed on average).CONCLUSION: Independent practice pattern for operative vaginal delivery reflects residency training for both vacuums and forceps.

Objectives-The gestation-adjusted projection method extrapolates birth weight using third-trimester sonography. This technique is shown to be more accurate for sonographic examinations from 34 weeks to 36 weeks 6 days than 37 weeks to 38 weeks 6 days. Our objective was to determine whether even earlier sonographic examinations (31 weeks-33 weeks 6 days) further improves birth weight prediction in patients with diabetes.Methods-We conducted a retrospective cohort analysis of 388 pregnant women with pregestational or gestational diabetes who delivered at 37 weeks or later and had a sonographic examination performed between 31 weeks and 36 weeks 6 days. Sonographic examinations were categorized as "early" if performed at 31 weeks to 33 weeks 6 days or "late" if performed at 34 weeks to 36 weeks 6 days. We estimated birth weight using the gestation-adjusted projection method, compared errors in prediction of birth weight using the t test and Mann-Whitney U test, and performed a 2-sample test of proportions to compare prediction of macrosomia (birth weight >4000 g).Results-The early and late groups had similar mean gestational ages at birth (38 weeks 4 days versus 38 weeks 5 days; P = .13) and rates of macrosomia (10.7% versus 12.4%; P = .63). The early group had a greater mean absolute error (336 versus 297 g; P = .03) and percent error (9.9% versus 7.9%; P = .01) in birth weight prediction but a lower mean birth weight (3303 versus 3426 g; P = .02). Sensitivity for prediction of macrosomia was 19% in the early group versus 45% in the late group (P = .07), whereas specificity was similar (98% versus 96%; P = .27).Conclusions-Using the gestation-adjusted projection method in our patients with diabetes, we found that sonographic examinations performed at 34 weeks to 36 weeks 6 days better predicted birth weight than those performed at 31 weeks to 33 weeks 6 days.

Objective: Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PIGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin.Study design: Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60 mg/d (n = 102) or placebo (n = 72), with PlGF collected at 13w 0 d-16 w 6 d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders.Results: ROC analysis indicated 87.71 pg/ml as the threshold between high and low PIGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p = 0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p = 0.445).Conclusions: Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PIGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated.Condensation: High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. (C) 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

OBJECTIVE: We aimed to determine whether a threshold number of forceps deliveries in residency predicts use of forceps in independent practice.STUDY DESIGN: We surveyed obstetrics and gynecology residency graduates of 2 academic programs from 2008 through 2012 regarding the use of operative vaginal delivery in practice. At these programs, residents are trained in both forceps and vacuums. Individual case log data were obtained with the number of forceps deliveries performed by each respondent during residency. Respondents were grouped as currently using any forceps or vacuums alone. A logistic regression model estimated the probability of forceps use, predicted by the number of residency forceps deliveries. From the resulting receiver-operating characteristic curve, we assessed sensitivity, specificity, positive predictive value, and area under the curve.RESULTS: The response rate was 85% ( n = 58) and 90% ( n = 52) practice obstetrics. Seventy-nine percent ( n = 41) use forceps in practice. The mean number of forceps performed during residency was 22.3 +/- 1.3 ( mean +/- SE) in the any-forceps group and 18.5 +/- 2.1 in the vacuums-only group (P = .14). Although the model performed only moderately (area under the curve, 0.61, 95% confidence interval [CI], 0.42-0.81), more than 13 residency forceps deliveries corresponded to a 95% sensitivity (95% CI, 84-99) and a positive predictive value of 83% (95% CI, 69-92) for using forceps in practice. The specificity of this threshold is 27% (95% CI, 6-61).CONCLUSION: Although exceeding 13 forceps deliveries made it highly likely that obstetricians would use them in practice, further study is necessary to set goals for a number of resident forceps deliveries that translate into use in practice.

Neonatal adiposity is associated with obesity later in life. Identifying fetuses with early signs of increased adiposity may allow for future research aimed at reducing excess fat accretion in utero, with the goal of limiting long-term metabolic sequelae associated with prenatal nutritional excess. Our objective was to determine whether soft tissue measurements of the fetal arm and leg by ultrasound (U/S) at 28 weeks (w) are predictive of neonatal body fat. In this prospective observational cohort study of healthy singleton pregnancies, we performed U/S at 28w with standard biometry and soft tissue measurements of the fetal upper arm and thigh (fractional limb volume, mid-limb cross-sectional area). We assessed neonatal body composition using skin folds and air displacement plethysmography (PEAPOD), and adjusted neonatal % body fat (%BF) to 40w0d by ±0.1%/day. We determined Spearman correlations between U/S findings and %BF, and performed modeling to predict neonatal adiposity using maternal characteristics and U/S findings. Our analysis included 32 women with mean maternal age of 30y and neonatal birth weight 3382g. Mean neonatal %BF was 8.1% by skin folds (2d of life) and 12.2% by PEA POD (15d). Correlations between U/S and %BF were generally stronger with PEA POD than with skin fold measurements. Fractional leg volume (FLV) provided the highest correlation with neonatal body fat (r=0.71; 95% confidence interval 0.37, 0.88), better than all other ultrasound measurements including the abdominal circumference (r=0.5; 0.13, 0.74) and estimated fetal weight (r=0.49; 0.14, 0.74). Our best model to predict neonatal body fat included only the FLV (R2=0.697, p<0.001). Soft tissue measurements of the fetal thigh at 28w correlated well with neonatal body fat. After validation in a larger cohort, fractional limb volume may be explored as a marker of abnormal fetal adiposity that could be targeted in prenatal interventional strategies for the prevention of excess fat at birth.

To determine whether the rate of preterm birth is affected by obesity in women with twin pregnancies exposed to 17 Alpha-Hydroxyprogesterone (17 OHP). This is a secondary analysis of the NICHD MFMU Network's "Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Multifetal Gestation", twin stratum (STTARS twins). All twin pregnancies assigned to 17 OHP were identified for this analysis; fetal anomalies were excluded. Rates of preterm birth before 35 weeks were compared for weight and BMI strata. We identified 634 women with twin pregnancies who met inclusion criteria; 226 (35%) had pre-pregnancy weight = 75, 324 (51%) had BMI = 25, 176 (28%) BMI =30, 70 (11%) BMI = 35, and 26 (4.1%) BMI = 40. Among women receiving 17 OHP, those with pre-pregnancy weight < 75kg were significantly less likely to have a preterm delivery compared to women with pre-pregnancy weight = 75kg (37% vs 48%, p=0.007). When stratified by BMI, there was a lower rate of preterm birth before 35 weeks for non-obese women (BMI<30 vs =30; 38% vs 48%, p=0.025) and non-morbidly obese women (BMI<40 vs =40; 40% vs 62%, p=0.027). Obesity increases the risk of preterm delivery for twin pregnancies in women exposed to 17 OHP.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a neuroautoimmune disease commonly associated with ovarian teratomas. It is characterized by neuropsychiatric symptoms, seizures, and autonomic instability. Few cases are described in pregnancy, and little is known about potential fetal effects.CASE: Anti-NMDA receptor encephalitis was diagnosed at 24 weeks of gestation. No improvement occurred with intravenous immunoglobulin, methylprednisolone, and plasmapheresis. Imaging was unremarkable. Cesarean delivery with concurrent bilateral oophorectomy resulted in prompt maternal improvement. Antibody titers were positive in cord blood.CONCLUSION: Anti-N-methyl-D-aspartate receptor encephalitis in pregnancy can lead to NMDA receptor antibodies in the fetal circulation. Pregnancy interruption through early delivery with or without oophorectomy may accelerate maternal recovery.

Objective: Early initiation of low-dose aspirin (LDA) may reduce preeclampsia risk. We sought to determine whether LDA was beneficial when initiated <17w0d, within a trial of high-risk women enrolled <26w0d. Study Design: Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin study, including women enrolled <17w0d, randomized to LDA (60 mg day −1 ) or placebo with chronic hypertension (CHTN, n =186), diabetes ( n =191) or prior preeclampsia ( n =146). The primary outcome was preeclampsia at any time in pregnancy, secondary outcomes were early preeclampsia (<34w0d), late preeclampsia (⩾34w), small for gestational age (SGA; neonatal birthweight <10th %) and composite (early preeclampsia or SGA). Outcomes were compared by exact Χ 2 -tests. Results: Baseline characteristics were similar between treatment groups. Aspirin was associated with a lower rate of late-onset preeclampsia ⩾34w (17.36% vs 24.42%, P =0.047), with a 41% reduction in women with CHTN (18.28% vs 31.18%, P =0.041). There were no other significant differences in the outcome. Conclusion: Aspirin initiated <17w0d reduced the risk for late-onset preeclampsia by 29% supporting the practice of early initiation of aspirin in high-risk women.

Previously, a large MFMU trial (HIRA) found no benefit to low-dose aspirin (ASA) initiated at 13-26w in women at high risk for preeclampsia (preE). Subsequent analyses found benefit with initiation of ASA prior to 17w, however the ideal candidate for ASA remains unclear. The objective of this analysis was to better understand which women would benefit from early initiation of ASA for the improvement of pregnancy outcome. This is a secondary analysis of the MFMU High-Risk Aspirin study (1991-1995), including singleton pregnancies enrolled ≤16w6d, with chronic hypertension (HTN, n=186), diabetes (DM, n=191), or preeclampsia in a prior pregnancy (n=146). Women were randomized to ASA (60mg daily) or placebo in a double-blinded protocol. Differences in baseline characteristics and outcomes of interest [early preeclampsia (<34w0d), late preeclampsia (≥34w), a small-for-gestational age neonate (SGA, <10%), or a composite outcome (early preeclampsia or SGA)] were assessed by treatment group and within each high-risk subgroup using exact Chi-square tests. There were no significant differences in baseline demographic characteristics between treatment groups. Overall, ASA reduced the risk for late preeclampsia (17.36 vs 24.42%, p=0.047), but not early preeclampsia (4.91 vs 3.10%, p=0.152), SGA (9.43 vs 10.85%, p=0.591), or the composite outcome (9.43 vs 10.22%, p=0.376). In subgroup analysis, women with HTN stood-out as benefitting from ASA, with a lower rate of late preeclampsia (>34w) relative to placebo (Figure 1). There were no other significant differences in outcome after early initiation of ASA in women with diabetes or prior preeclampsia. Among singleton pregnancies at increased risk for preeclampsia due to chronic HTN, DM, or a history of prior preeclampsia, only those with chronic HTN benefited from early aspirin administration. The most morbid outcomes, early preeclampsia and SGA, were not significantly lessened by early initiation of ASA prophylaxis.

Low placental growth factor (PlGF) levels early in pregnancy are associated with later development of preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk populations. The objective of this analysis was to determine whether PlGF levels in early pregnancy could be used to identify a subgroup of women likely to benefit from early initiation of low-dose aspirin. This is a secondary analysis of the MFMU High-Risk Aspirin study (1991-1995) including singleton pregnancies enrolled ≤16w6d, with baseline PlGF levels collected at enrollment. Women were randomized to aspirin 60mg daily (n=102) or placebo (n=72) in a double-blinded protocol. Among women randomized to placebo, logistic regression modeling was used to estimate the probability of preeclampsia by PlGF level, and ROC analysis was utilized to determine a potential "low" PlGF threshold to predict preeclampsia. Comparison of preeclampsia rates in all pregnancies with "low" baseline PlGF levels was then performed by treatment group with an exact Chi-square test. Baseline characteristics were compared by group with exact Chi-square tests. There were no significant differences between the aspirin and placebo groups in baseline demographic characteristics, baseline PlGF levels (90.4 vs 102.0 pg/ml, P=0.376), or preeclampsia rates (19 vs 22%, p=0.56). ROC analysis yielded a PlGF threshold of 87.71 pg/ml, below which the sensitivity and specificity for the prediction of preeclampsia was 63% and 66%, with AUC of 0.653. Subsequent comparison of preeclampsia rates in all pregnancies with "low" baseline PlGF yielded no difference in the rate of preeclampsia between aspirin and placebo groups (21.7 vs 15.9%, P=0.445). The impact of low PlGF on preeclampsia risk was not modified by early initiation of low-dose aspirin. PlGF levels may be useful in triaging patients to heightened preeclampsia surveillance, but should not be used to guide decision-making regarding aspirin prophylaxis.