Faculty Bibliography

Abstract Objective: The objective was to determine if the rate of abnormal biochemical markers is different in pregnancies conceived by donor oocyte versus those conceived by autologous oocytes. Methods: This is a retrospective cohort study of patients who underwent risk assessment for aneuploidy. Pregnancies conceived by egg donation were matched with control groups who conceived using their own eggs. The primary outcomes were incidence of low PAPP-A or free bHCG in the first trimester or elevated MSAFP, free bHCG or Inhibin A, or low uE3 in the second trimester. Results: 260 singleton gestations were identified who conceived via oocyte donor. There was a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (8% versus 2%, p = 0.028) compared to a control group matched by maternal age. There was also a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (7% versus 2%, p = 0.01) compared to a control group matched by age of the egg donor. Conclusion: Pregnancies conceived by egg donation are more likely to have an unexplained elevation in MSAFP compared to pregnancies not conceived by egg donation regardless of age. Egg donation itself is not associated with other biochemical abnormalities.

Abstract Objective: To estimate whether the severity of uterine anomaly is associated with the risk of adverse pregnancy outcomes. Methods: Retrospective cohort study of patients delivered by one maternal fetal medicine group from 2005 to 2012. We included 158 patients with a singleton pregnancy and a uterine anomaly, as well as an equal number of randomly selected unexposed singleton pregnancies delivered by the same group. Patients with uterine anomalies were subdivided into those with major fusion defects (unicornuate, bicornuate and didelphys) and minor fusion defects (arcuate, septate and t-shaped). Results: The incidence of adverse pregnancy outcomes increased across unexposed patients, patients with minor fusion defects and patients with major fusion defects. These included preterm birth < 37 weeks, preterm birth < 35 weeks, birth weight < 10th percentile, birth weight < 5th percentile, preeclampsia, malpresentation and cesarean delivery. Conclusion: The incidence of adverse pregnancy outcomes and cesarean delivery is increased in patients with minor fusion defects and is further increased in patients with major fusion defects.

Abstract Objective: To report blood pressure (BP) across gestation in patients with twin pregnancy. Methods: Historical cohort of all twin pregnancies managed by one maternal-fetal medicine practice from 2005 to 2012. Patients with chronic hypertension were excluded. We reviewed all outpatient BP measurements taken during pregnancy and compared systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) for every 2-week interval starting at 6 weeks. All BP measurements were taken manually in the seated upright position. Results: There were 520 patients with twin pregnancies managed over the study period, 19 (3.7%) were excluded for chronic hypertension, leaving 501 patients for analysis. There were a total of 4985 BP measurements (9.95 per patient) during pregnancy. Starting at 6 weeks' gestation, the SBP, DBP and MAP remained stable until 30 weeks' gestation, when all three began to rise significantly until 38 weeks (p < 0.001). There was no drop in BP in the second trimester. The 95th percentile for systolic BP did not exceed 121 mmHg until 30 weeks and the 95th percentile for diastolic BP did not exceed 80 mmHg until 34 weeks. The 4 - to 10-week postpartum DBP and MAP were significantly higher than the initial DBP and MAP <10 weeks. Conclusions: In patients with twin pregnancies, the BP remains stable from 6 weeks until 30 weeks, at which time it begins to rise steadily. The 95th percentile for SBP and DBP prior to 30 weeks are approximately 120 and 80 mmHg, respectively.

Abstract Objective: To determine whether routine cervical length (CL) and fetal fibronectin (fFN) screening is associated with improved clinical outcomes in asymptomatic patients with twin pregnancies. Study design: We compared outcomes between two large cohorts of twin pregnancies who delivered in New York City from 2003 to 2012. One cohort (n = 532) was managed by a single group practice, delivered at one large academic medical center, and underwent routine serial CL and fFN screening. The second cohort (n = 456) delivered at a second large academic center and only underwent CL and fFN testing as clinically indicated. Outcomes measured include cerclage placement, preterm birth (PTB), spontaneous PTB (sPTB), and antenatal corticosteroid (ACS) exposure. Results: Rates of cerclage placement, PTB, and SPTB were similar between the two groups. However, routine CL and fFN screening was associated with improved rates of ACS exposure in patients who delivered <34 weeks (91.3% versus 74.7%, p = 0.005) and 34-36 6/7 weeks (41.3% versus 13.9%, p < 0.001) without increased ACS exposure in women who delivered at term. In patients who delivered <34 weeks, routine CL and fFN screening was significantly associated with improved rates of ACS exposure within 1-14 days of delivery and within 1-7 days of delivery. Conclusion: In twin pregnancies, routine CL and fFN screening does not reduce the risk of PTB or SPTB. However, the routine use of these tests is associated with significantly improved ACS exposure and timing for women who deliver preterm without increasing ACS exposure to women who deliver at term.

OBJECTIVE: To describe pregnancy characteristics associated with the occurrence of spontaneous version in twin pregnancies from 20 weeks until delivery. STUDY DESIGN: Review of ultrasound and pregnancy data for all twin pregnancies delivered >24 weeks by one Maternal-Fetal Medicine practice from June 2005-May 2012. For each 4-week gestational age window, fetal presentations were recorded, as well as the likelihood of the final presentation being vertex for Twin A and vertex for both twins. Case-control analysis was performed to estimate associations between pregnancy characteristics and spontaneous version of Twin A. RESULTS: A total of 491 twin pregnancies were included. The distribution of fetal presentations changed significantly from 20 weeks to delivery, but the presentation at each gestational age interval was significantly associated with the final position of Twin A and the likelihood of vertex-vertex presentation at delivery. The likelihood of spontaneous version of Twin A decreased from 27.9% after 24-27 6/7 weeks, to 18.8% after 28-31 6/7 weeks, to 8.2% after 32-35 6/7 weeks. Pregnancy characteristics associated with spontaneous version of Twin A were a prior vaginal delivery and increased fetal size of either twin. CONCLUSIONS: The likelihood of spontaneous version of Twin A decreases as pregnancy advances. Parity and increased fetal size are associated with spontaneous version.

OBJECTIVE: To estimate the effectiveness of antepartum surveillance and delivery at 41 weeks in reducing the risk of stillbirth in advanced maternal age (AMA) patients. STUDY DESIGN: Retrospective cohort study of all patients managed in one maternal-fetal medicine practice from June 2005 to May 2012. We included all singleton pregnancies delivered at >/=20 weeks of gestation. All AMA patients (age >/=35 years at their estimated delivery date) underwent weekly biophysical profile testing beginning at 36 weeks, as well as planned delivery at 41 weeks, or sooner if indicated. We compared the rate of fetal death at >/=20 weeks and fetal death at >/=36 weeks in AMA vs. non-AMA patients. Fetal deaths due to lethal and chromosomal abnormalities were excluded. RESULTS: 4469 patients met the inclusion criteria: 1541 (34.5%) were AMA and 2928 (65.5%) were non-AMA. Using our AMA protocol for surveillance and timing of delivery, the incidence of stillbirth was similar to the non-AMA population (stillbirth >/=20 weeks: 3.9 per 1000 vs. 3.4 per 1000, p=0.799; stillbirth >/=36 weeks: 1.4 per 1000 vs. 1.1 per 1000, p=0.773). When looking at women age <35, age 35-39, and age >/=40, the incidence of stillbirth >/=20 weeks and >/=36 weeks did not increase across the three groups. Our findings were similar when we excluded all patients with other indications for antepartum surveillance. CONCLUSIONS: In AMA patients, antepartum surveillance and delivery at 41 weeks appears to reduce the risk of stillbirth to that of the non-AMA population. Routine antepartum surveillance should be considered in all AMA patients.

Objective To determine if prophylactic cerclage improves pregnancy outcomes in women with twin pregnancies without a history of cervical insufficiency.Study Design Women with twin pregnancies who received outpatient preterm labor surveillance services between January 1990 and May 2004 for >/=1 day beginning at < 28.0 weeks' gestation were identified from a database. Patients with previous preterm delivery or a diagnosis of cervical incompetence in a previous or in the index pregnancy were excluded. Twin pregnancies managed with prophylactic cerclage were compared with twin pregnancies in which cerclage was not placed. The primary outcome was incidence of preterm birth prior to 32 weeks. Groups were compared using Fisher exact and Mann-Whitney U test statistics.Results Overall, 8,218 twin pregnancies met inclusion criteria, of which 146 women (1.8%) received prophylactic cerclage. Patients who received prophylactic cerclage had a significantly higher incidence of preterm birth before 32 weeks and infants with lower mean birth weight and longer nursery stays. No significant difference was seen in mean gestational age at delivery. This study had 80% power to detect a 7% reduction in the primary outcome.Conclusion Prophylactic cerclage was not associated with a lower risk of preterm birth and adverse neonatal outcomes in twin pregnancies without history of cervical insufficiency.

BACKGROUND: A randomized study published in 2003 by the National Institute of Child Health and Human Development Maternal Fetal Medicine Units network showed efficacy of 17-alpha hydroxyprogesterone caproate (17P) for the prevention of recurrent preterm delivery. Between 2003 and 2011 the drug was often provided by compounding pharmacies. In 2011, the US Food and Drug Administration (FDA) approved the drug for this indication. OBJECTIVE: The objective of this study was to evaluate the impact of FDA approval on physician attitudes and perceptions regarding use of 17P as a drug for preventing recurrent preterm delivery. METHODS: A 10-min online survey using a structure closed-ended questionnaire format was designed and administered from 17 June 2011 to 7 July 2011 among 401 obstetricians distributed evenly throughout the USA. RESULTS: There is nearly universal awareness of 17P for the prevention of preterm birth (93 %), with a large majority (80 %) of obstetricians having reported prescribing the medication. However, surveyed physicians reported that the average proportion of eligible patients seen in their practice but not prescribed 17P in 2009-2010 was 41 %. Financial and logistical barriers carried the most weight (approximately 75 %) in the decision not to prescribe 17P to an eligible patient. Forty-one percent of respondents cited lack of FDA approval of 17P as a deterrent to prescribing the medication. Thirty-nine percent of respondents had professional liability concerns regarding prescribing compounded 17P. Assuming the same out-of-pocket expense for patients, two-thirds of obstetricians would choose to prescribe Makena((R)). CONCLUSION: Awareness of 17P for the prevention of preterm birth among obstetricians is high. FDA-approved medications seem to have physician preference due to enhanced assurance for product efficacy and safety.

This prospective, multi-center study investigated the utility of pre-conditioning test pharmacokinetics (PK) of intravenous busulfan (IV Bu) to optimize dosing in 204 subjects with Hodgkin (n=64) and B-cell non-Hodgkin lymphoma (n=140) at 32 centers in the US and Canada. PK studies were conducted twice during the study: test PK on Day -14 to -11 and confirmatory PK on the first day of conditioning, Day -8. The test PK used a 2-hour infusion of a single IV Bu dose (0.8 mg/kg) in order to determine the area under the concentration-time curve (AUC). The test PK dosing was based on adjusted ideal body weight (AIBW) for all patients except for the subjects whose actual BWwas less than or equal to the ideal BW, where actual BW was used. AIBW was calculated by adding 25% of the difference between ideal BW and actual BW to ideal BW. The conditioning dose of daily IV Bu was then calculated to achieve 20,000 mM*min as a total AUC. The same individualized Bu dose was administered over 3 hours once daily from Day -8 to Day -5. If needed, dose was further adjusted on Days -6 and -5 based on confirmatory PK results. VP-16 (1.4 g/m²) was administered on Day -4, followed by 2.5 g/m²/day of cyclophosphamide on Days -3 and -2. Test PK from 204 subjects showed that 6 subjects (2.9%) had higher AUC than expected (>1,500 mM*min) and 68 subjects (33.3%) had lower AUC (<1,000 mM*min). Therefore, total AUC would have fallen outside the target range in 74 subjects (36.3%) if PK-directed dose adjustment had not been performed. The discrepancy between expected and observed exposure was not predicted by subject height, actual body weight, body mass index (BMI) or body surface area. For example, although a greater proportion of patients with high BMI were underexposed compared with those with normal BMI, the difference was not significant [Table 1]. In addition, all patients who had AUC>1,500 mM*min had normal or high BMI. Thus, it is not possible to prospectively identify the subpopulation which has a risk of suboptimal Bu exposure and would gain the most benefit from PK-directed dose optimization. Hence,PK-directed dose optimization should be considered for all subjects when tight regulation of Bu exposure is critical, and should not be limited to subpopulations. Out of 200 patients whose confirmatory PK results were evaluable, 190 subjects (95.0%) fell within the target range (AUC: 20,000 mM*min +/- 20%). Eight (4.0%) and two (1.0%) patients required dose reductions and increases, respectively, for the last two days of Bu dosing. Again, no predictive factor was identified for these patients. In conclusion, a pre-conditioning small dose of IV Bu estimated individual PK parameters and predicted Day-8 PK in 95% of the subjects. This relatively large PK study identified no factor that could predict outliers linked to Bu metabolism. Therefore, when Bu exposure has to be tightly controlled, PK-directed dose optimization should be conducted for all patients. (Table Presented)