Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis-A Large Retrospective Case Series.

Osteoarthritis (OA) of the knee is a leading cause of chronic pain and disability in the United States. Current treatment options primarily target OA symptoms reserving surgical intervention and knee replacement for those who fail conservative measures. With average age of patients with knee OA decreasing, regenerative treatment approaches to reduce symptoms, increase quality of life, and delay the need for surgical intervention are increasingly sought. Human amniotic membrane contains growth factors and cytokines, which promote epithelial cell migration and proliferation, stimulate metabolic processes leading to collagen synthesis, and attract fibroblasts, while also reducing pain and inflammation. Micronization of the tissue allows for suspension in normal saline and injection. We conducted a retrospective review of 100 knees treated for symptomatic OA with micronized dehydrated human amnion/chorion membrane (mdHACM) and followed for 6 months. Our purpose is to present our experience and patient outcomes. Data were abstracted from electronic medical records of 82 consecutive OA patients (100 knees) injected with 100 mg mdHACM. Patient age, gender, adverse events and routinely collected Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated. Effectiveness of mdHACM treatment was measured by serial KOOS at baseline, and posttreatment at 6 weeks, 3, and 6 months. Overall mean KOOS for the cohort was 40 at baseline, improving to 52, 62, and 65 at 6 weeks, 3 months, and 6 months post-mdHACM injection. Percent increases were 32, 56, and 65%, respectively. Quality of life and sports/recreation domains improved by 111 and 118%, respectively, at 6 months. Pain scores improved by 67% at 6 months. All scores improved throughout the observation period. The most common adverse event was pain after injection lasting 2 to 7 days, observed in 68% of cases. This represents the largest single-physician experience with mdHACM for treatment of knee OA reported to date. Injectable mdHACM appears to be a potentially useful treatment option for knee OA patients. Controlled studies are underway to confirm these observations.

Spontaneously conceived pregnancy after 40: influence of age and obesity on outcome.

OBJECTIVE: The aim of the study was to examine pregnancy outcomes of healthy nulliparous women aged ≥ 40 years at delivery. STUDY DESIGN: The study included 53,480 nulliparous women aged 20 to 29 or ≥ 40 years delivering singleton infants, enrolled in a pregnancy risk assessment program between July 1, 2006, and August 1, 2011. Women reporting medical disorders, tobacco use, or conception with assistive reproductive technology were excluded. Data were grouped by body mass (obese or nonobese) and age (20-29 or ≥ 40 years). Pregnancy outcomes were compared within each body mass group for women aged 20 to 29 years versus ≥ 40 years and between obese and nonobese women aged ≥ 40 years. RESULTS: Within each body mass group, nulliparous women aged ≥ 40 years delivered at a significantly lower gestational age and had a greater incidence of cesarean delivery, gestational diabetes, preterm birth, and both low and very low birth weight infants, compared with controls aged 20 to 29 years. For women aged ≥ 40 years, obesity was associated with higher rates of adverse pregnancy outcomes. CONCLUSION: In healthy women, both advanced maternal age and obesity negatively influence pregnancy outcomes. Women who delay pregnancy until age 40+ years may modify their risk for cesarean section, preterm birth, and low-birth-weight infants by reducing their weight to nonobese levels before conception.

Timing and consequences of early term and late term deliveries.

OBJECTIVE: To examine the timing of elective delivery and neonatal intensive care unit (NICU) utilization of electively delivered infants from 2008 to 2011. METHODS: Analysis included 42,290 women with singleton gestation enrolled in a pregnancy education program, reporting uncomplicated pregnancies with elective labor induction (ELI) (n = 27,677) or scheduled cesarean delivery (SCD) (n = 14,613) at 37.0-41.9 weeks' gestation. Data were grouped by type and week of delivery (37.0-37.9, 38.0-38.9, and 39.0-41.9 weeks). ELI and SCD for each week of delivery from 2008 to 2011 and nursery utilization by delivery week were compared. RESULTS: During the 2008-2011 timeframe, a shift in timing of ELI and SCD toward ≥39.0 weeks was observed. In 2008, 80.9% of ELI occurred at ≥39.0 weeks versus 92.6% in 2011 (p < 0.001). In 2008, 60.5% of SCD occurred at ≥39.0 weeks versus 78.1% in 2011 (p < 0.001). NICU admission and prolonged nursery stays were highest at 37.0-37.9 weeks for both groups. CONCLUSIONS: We observed a shift toward later gestational age at elective delivery from 2008 to 2011 and increased NICU utilization for neonates born at <39 weeks' gestation.

Pregnancy outcomes of women receiving compounded 17 α-hydroxyprogesterone caproate for prophylactic prevention of preterm birth 2004 to 2011.

OBJECTIVE: To examine pregnancy outcomes of women receiving weekly compounded 17 α-hydroxyprogesterone caproate (17P) injections through a home nursing program compared with those reported in a multicenter trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Network. METHODS: The study sample was comprised of patients receiving compounded 17P through a home nurse administration care management program. Included were women with current singleton gestation and prior spontaneous preterm birth (SPTB) initiating 17P between 16 and 20 weeks. Maternal characteristics and pregnancy outcomes were compared between study group and NICHD Network trial patients. RESULTS: Women (n = 5493) received a mean of 16.9 ± 4.0 injections. Of the 92,700 injections, 98.4% were administered within the recommended 5- to 9-day interval. Recurrent SPTB occurred in 28.3%. The overall rate of SPTB at <37 weeks was similar for black and nonblack women (p = 0.592). Within black or nonblack groups, preterm birth rates at <37 weeks were similar regardless of gestational age at start of 17P (p = 0.894 and p = 0.374, respectively). These results were similar to those reported in the multicenter trial. Fetal and neonatal death occurred in 0.8% (46/5493). No significant difference was observed in rate of fetal or neonatal death by gestational age at initiation of 17P (p = 0.478). CONCLUSION: Home nurse administration of compounded 17P is safe and effective.

17-alphahydroxyprogesterone caproate in women with previous spontaneous preterm delivery: does a previous term delivery affect the rate of recurrence?

OBJECTIVE: The purpose of this study was to determine the role of previous term delivery on the rate of recurrent preterm birth in women with previous spontaneous preterm delivery (SPTD) who receive 17-alphahydroxyprogesterone caproate (17P) therapy. STUDY DESIGN: Women with singleton gestations who were receiving 17P therapy were studied. Rates of recurrent SPTD were compared for 1 or ≥2 SPTD with and without a previous term delivery. RESULTS: Five thousand one hundred two women had 1 previous SPTD, and 2217 women had ≥2 SPTDs. In women with 1 previous SPTD, a previous term delivery had lower rates of SPTD at <35 weeks (8.4% vs 11.2%; P = .002) and preterm delivery at <32 weeks (4.7% vs 6.2%; P = .027) compared with those women with no such history. No differences were found for SPTD at <35 weeks with ≥2 SPTDs. CONCLUSION: In patients who received 17P therapy with 1 previous SPTD, a previous term delivery confers a reduction in risk of preterm delivery at <37, <35, and <32 weeks' gestation; such reduction is not evident with ≥2 previous SPTDs.

Influence of gestational age and reason for prior preterm birth on rates of recurrent preterm delivery.

OBJECTIVE: We sought to compare rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17-α-hydroxyprogesterone caproate (17P) with prior SPTB due to preterm labor (PTL) vs preterm premature rupture of membranes (PPROM). STUDY DESIGN: Women with singleton gestation having 1 prior SPTB enrolled at 16-24.9 weeks' gestation for weekly outpatient 17P administration were identified from a database. Rates of recurrent SPTB were compared between those with prior SPTB due to PTL or PPROM overall and by gestational age at prior SPTB. RESULTS: Records from 2123 women were analyzed. The prior PTL group vs the prior PPROM group experienced higher rates of recurrent SPTB at <37 weeks (29.7% vs 22.9%, P = .004), <35 weeks (14.0% vs 9.1%, P = .004), and <32 weeks (5.9% vs 3.3%, P = .024), respectively. CONCLUSION: Reason and gestational age of prior SPTB influence the likelihood of recurrent SPTB in women receiving 17P prophylaxis.

New gestational weight gain guidelines: an observational study of pregnancy outcomes in obese women.

In 2009, the Institute of Medicine (IOM) revised their pregnancy weight gain guidelines, recommending gestational weight gain of 11-20 pounds for women with prepregnancy BMI >30 kg/m(2). We investigated the potential influence of the new guidelines on perinatal outcomes using a retrospective analysis (n = 691), comparing obese women who gained weight during pregnancy according to the new guidelines to those who gained weight according to traditional recommendations (25-35 pounds). We found no statistical difference between the two weight gain groups in infant birth weight, cesarean delivery rate, pregnancy-related hypertension, low birth weight infants, macrosomia, neonatal intensive care unit admissions, or total nursery days. Despite showing no evidence of other benefits, our data suggest that obese women who gain weight according to new IOM guidelines are no more likely to have low birth weight infants. In the absence of national consensus on appropriate gestational weight gain guidelines, our data provide useful data for clinicians when providing evidence-based weight gain goals for their obese patients.

Elective delivery at 34°(/)7 to 366(/)7 weeks' gestation and its impact on neonatal outcomes in women with stable mild gestational hypertension.

OBJECTIVE: To examine the frequency of elective delivery and neonatal outcomes in women with stable mild gestational hypertension delivering late preterm. STUDY DESIGN: The frequency of elective delivery between 1995 and 2007 at gestational age of 34°(/)7-366(/)7 weeks (late preterm), 37°(/)7-376(/)7 weeks, and ≥38°(/)7 weeks, as well as neonatal outcomes, were studied in singleton gestation with mild gestational hypertension without proteinuria from a large national database. RESULTS: One thousand eight hundred fifty-eight patients were studied: 607 (33%) were delivered for maternal/fetal reasons and 1251 (67%) were electively delivered. Among the 1251 women delivered electively, 25.5% were late preterm, 24.4% at 37°(/)7-376(/)7 weeks and 50.1% at ≥38°(/)7 weeks' gestation. Neonatal intensive care unit admission, ventilatory assistance, and respiratory distress syndrome were more common in late-preterm infants. There was no maternal/perinatal mortality. CONCLUSION: We found that 25.5% of patients with stable mild gestational hypertension, without any maternal or fetal complication, had iatrogenic elective late-preterm delivery. This practice also was associated with increased rates of neonatal complications and neonatal length of stay.

Impact of prior gestational age at preterm delivery on effectiveness of 17-alpha-hydroxyprogesterone caproate in practice.

OBJECTIVE: We sought to examine if 17-alpha-hydroxyprogesterone caproate (17OHPC) effectiveness is dependent on the earliest gestational age (GA) at prior spontaneous preterm birth (SPTB) when administered in the clinical setting. STUDY DESIGN: Women enrolled for outpatient services with current singleton gestation and > or =1 prior SPTB between 20-36.9 weeks were identified. Data were divided into 3 groups according to earliest GA of prior SPTB (20-27.9, 28-33.9, and 34-36.9 weeks). We compared GA at delivery of current pregnancy and incidence of recurrent SPTB between women enrolled in outpatient 17OHPC administration program (n = 2978) and women receiving other outpatient services without 17OHPC (n = 1260). RESULTS: Rates of recurrent SPTB for those with and without 17OHPC prophylaxis, respectively, according to GA at earliest SPTB were: 20-27.9 weeks at earliest SPTB, 32.2% vs 40.7%, P = .025; 28-33.9 weeks at earliest SPTB, 34.1% vs 45.5%, P < .001; and 34-36.9 weeks at earliest SPTB, 29.3% vs 38.8%, P < .001. CONCLUSION: 17OHPC given to prevent recurrent SPTB is effective regardless of GA at earliest SPTB.

Using 17 α-hydroxyprogesterone caproate to impact rates of recurrent preterm delivery in clinical practice.

OBJECTIVE: Evaluation of an outpatient 17 α-hydroxyprogesterone caproate (17P) administration programme. METHODS: A retrospective analysis of data collected from patients with a history of preterm birth (PTB) and current singleton gestation enrolled between 16.0 and 20.9 weeks' gestational age (GA) for weekly outpatient 17P administration and nursing assessment between 7/2004 and 12/2007 was conducted (n=3139). RESULTS: The population was mostly white (50.3%), 18-35 years old (77.7%), and married (67.0%). Median GA at 17P initiation and stop was 17.4 (16.0, 20.9) weeks and 35.1 (18.6, 37.4) weeks. Mean injections per patient were 16.5±4.9, at an interval of 7.2 days. Median GA at delivery was 37.3 (18.6, 44.0) weeks. Rate of recurrent spontaneous PTB was 29.8%, with 15.5% and 7.0% with PTB at <35 and <32 weeks. CONCLUSIONS: This represents the largest cohort reported to date of patients prescribed 17P therapy in clinical practice to prevent recurrent spontaneous PTB.

The reliability of patient-reported pregnancy outcome data.

Pregnancy and neonatal outcome information is frequently used in disease management to evaluate the cost-effectiveness of prenatal interventions and for other research and reporting activities. The purpose of this study was to determine if a telephone interview process is a reliable methodology for collecting pregnancy outcomes. High-risk patients from a large maternal-fetal medicine practice who received outpatient preterm labor management services from January 1996 to June 2001 were identified. Patient-reported pregnancy outcome data for 285 mothers and 478 infants were collected via a telephone interview by a perinatal nurse and compared to pregnancy outcome data abstracted from the maternal and infant hospital records. Overall, concordance and/or Kappa coefficients between maternal report and the medical record were high for delivery date (96.4%), birth weight within 100 grams (88.9%), Cesarean delivery (99.0%, Kappa = 0.98), and high-level nursery admission (91.2%, Kappa = 0.82). Both singleton and multiple gestation types accurately reported pregnancy outcome information. A telephone interview with a skilled nurse can be a reliable methodology for collection of valuable clinical and research data related to pregnancy outcome. Data collected in this manner and maintained in a database may be used with a high level of confidence by health care providers, payers, and researchers.

Uterine activity in women receiving 17 alpha-hydroxyprogesterone caproate for the prevention of preterm birth: an observational study.

We evaluated uterine contraction frequency in women receiving 17 alpha-hydroxyprogesterone caproate (17-OHP-C) for the prevention of preterm delivery. Women with singleton pregnancies and receiving weekly 17-OHP-C and outpatient tococardiography were identified from a database. The mean and maximum contraction frequencies per hour were compared from 3 days before to 3 days after 17-OHP-C dosing. McNemar chi(2), Mann-Whitney U, and Friedman test statistics were used for analysis. Data were obtained from 388 women. Median contraction frequency was greater for women with subsequent preterm birth versus those delivering at term (1.5 [range 0, 14.5] versus 1.2 [range 0, 21.0] contractions per hour, P < 0.001). No reduction in contraction frequency was observed after 17-OHP-C administration, and in fact, the converse was observed for the average contractions 3 days prior compared with 3 days posttreatment ( P < 0.001). In the subgroup of women with a subsequent spontaneous preterm, the proportion who had an average contraction frequency of more than five per hour 1 day preinjection versus 1 day postinjection was not significantly different (2.6% versus 3.0%, P = 1.0). Administration of 17-OHP-C was not associated with a reduction in contraction frequency. To be effective, this drug likely has effects by mechanisms other than tocolysis. Although a statistically significant increase in contractions was identified posttherapy versus pretherapy, the clinical importance of this observation is unknown.

The risk for preterm labor in women receiving 17 alpha-hydroxyprogesterone caproate prophylaxis for preterm birth prevention.

We sought to identify maternal or clinical characteristics of women likely to develop preterm labor (PTL) at <34 weeks' gestation while receiving 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis. Current singleton gestations with prior preterm delivery enrolled for outpatient 17P administration at <27 weeks' gestation were identified ( N = 1177). Maternal and clinical characteristics were compared between women hospitalized and diagnosed with PTL at <34 weeks' gestation (PTL group, N = 270) and those without PTL (No PTL group, N = 660). PTL at <34 weeks' gestation occurred in 270/1177 (22.9%) of patients receiving 17P prophylaxis (mean gestational age at diagnosis was 28.3 +/- 4.0 weeks). Recurrent preterm delivery occurred in 73.3% of women with PTL at <34 weeks. Maternal age, marital status, race, tobacco use, cerclage, gestational age at start of 17P, and Medicaid status were similar between the groups. Women developing PTL at <34 weeks were more likely to have >1 prior preterm delivery than those without PTL (35.2% versus 25.9%, P = 0.006, odds ratio [95% confidence interval] 1.5 [1.1, 2.1]). Women receiving 17P prophylaxis remain at increased risk for PTL and preterm birth. Patient education and surveillance for PTL symptoms may be warranted in women with a history of more than one prior preterm delivery.

Preterm birth prevention by 17 alpha-hydroxyprogesterone caproate vs. daily nursing surveillance.

OBJECTIVE: To compare the incidence of spontaneous recurrent preterm delivery (SPTD) between women receiving 17 alpha-hydroxyprogesterone caproate (17P) and women receiving daily perinatal nursing surveillance (dPNS) with home uterine activity monitoring. STUDY DESIGN: Women enrolled for dPNS or weekly nursing visits with 17P injection were eligible. Included were singletons with previous SPTD, without preterm labor (PTL), cerclage or vaginal bleeding and < 27 weeks at enrollment. 17P and dPNS patients were matched 1:1 by race, marital status, tobacco use and number of SPTDs. Primary study outcome was incidence of spontaneous PTD. RESULTS: Data from 342 matched pairs were compared. Diagnosis of PTL (39.2% vs. 60.8%) and tocolytic use (12.9% vs. 49.7%) was decreased with 17P vs. dPNS (p < 0.001). The incidences of spontaneous PTD at < 32, 35 and 37 weeks were similar between the groups. CONCLUSION: There was no difference in recurrent SPTD between women treated with 17P and those receiving dPNS.

The impact of acute tocolysis on neonatal outcome in women hospitalized with preterm labor at 32 to 34 weeks' gestation.

We compared neonatal outcomes from singleton pregnancies in women hospitalized with preterm labor (PTL) at 32 0/7 to 34 6/7 weeks managed with and without acute tocolysis. Women enrolled for outpatient surveillance who were hospitalized and diagnosed with PTL between 32 0/7; to 34 6/7 weeks' gestation without conditions necessitating interventional delivery during hospitalization were identified ( N = 2921). Patients with contraindications to pregnancy prolongation were excluded ( N = 168). Data were compared between patients whose clinical management included tocolysis ( N = 2342) and patients in whom tocolysis was not utilized ( N = 411). The incidence of preterm birth (77.9% versus 48.1%), low birth weight (48.9% versus 16.7%), neonatal intensive care unit admission (41.4% versus 16.2%), and nursery length of stay > 7 days (28.0% versus 9.7%) were all higher in women not receiving acute tocolysis compared with the acute tocolysis group (all P < 0.001). Using acute tocolysis to prolong pregnancy in patients hospitalized with PTL at 32 0/7 to 34 6/7 weeks' gestation is associated with improved neonatal outcomes.

Antenatal factors predicting subsequent need for insulin treatment in women with gestational diabetes.

OBJECTIVE: To identify characteristics indicative of subsequent requirement of insulin in patients with gestational diabetes (GDM). METHODS: Identified from a database were patients with GDM not receiving insulin or oral hypoglycemic agents at enrollment for outpatient education and surveillance. Maternal characteristics were compared between patients achieving glycemic control with diet and those requiring insulin. Cox proportional hazards regression was used to assess multiple effects of significant univariate factors. RESULTS: Data from 2365 patients were analyzed. Patients requiring insulin were more likely to be multiparous, obese, have a history of GDM, be diagnosed at <28 weeks of gestation, and have a fasting blood glucose of >95 mg/dL, a glucose tolerance test 3-hour blood glucose of >140 mg/dL, and a glycosylated hemoglobin (A1c) of >or=6% at diagnosis of GDM. CONCLUSIONS: Laboratory values at diagnosis of GDM were the strongest indicators of subsequent need for insulin treatment. Patients with fasting blood glucose of >95 mg/dL and A1c values >or=6% at diagnosis of GDM should receive close surveillance of daily blood glucose.

Management of recurrent preterm labor in twin gestations with nifedipine tocolysis.

We examined outcomes of twin pregnancies complicated by recurrent preterm labor receiving nifedipine tocolysis. In a retrospective study design, twin pregnancies receiving outpatient preterm labor surveillance services and oral nifedipine tocolysis following a diagnosis of preterm labor were identified from a database ( N = 1421). Eligible for inclusion were patients subsequently rehospitalized with recurrent preterm labor symptoms ( N = 862). Included were patients at < 35 weeks' gestation, having intact membranes, and remaining undelivered for > 48 hours after recurrent preterm labor ( N = 656). Pregnancy outcomes of women resuming nifedipine tocolysis ( N = 418) following hospitalization were compared with those having an alteration in treatment ( N = 238) to continuous subcutaneous terbutaline. Alteration of tocolytic treatment versus resuming nifedipine resulted in increased pregnancy prolongation (34.7 +/- 18.8 days versus 27.5 +/- 19.9 days, P < 0.001), with delivery of fewer low birth weight (67.2% versus 78.3%, P < 0.001) and very low birth weight infants (6.5% versus 15.0%, P < 0.001) and a decreased incidence of neonatal intensive care unit admission (44.7% versus 52.9%, P = 0.005). In twin pregnancies receiving nifedipine tocolysis, alteration of tocolytic treatment to subcutaneous terbutaline following hospitalization for recurrent preterm labor symptoms had a positive impact on pregnancy prolongation and neonatal outcomes.

The use of 17 alpha-hydroxyprogesterone caproate (17p) in women with cervical cerclage.

Our objective was to compare the incidence of recurrent spontaneous preterm delivery (SPTD) in patients with cervical cerclage treated with weekly 17 alpha-hydroxyprogesterone caproate (17P) injections versus daily outpatient nursing surveillance (ONS) without 17P. Included in this retrospective cohort study were singleton gestations with cerclage placed at the discretion of the provider due to prior SPTD, delivering between January 1, 2004 and May 1, 2006. The study group (n = 232) consisted of women receiving once-weekly nursing visit and 17P injection. The control group (n = 1650) consisted of women enrolled for ONS (twice-daily electronic uterine contraction monitoring and nursing assessment). Data were further stratified by the number of prior preterm deliveries (1, > 1). Primary study outcome was the incidence of SPTD. No difference in rates of recurrent SPTD at < 37 or < 35 weeks were observed between the study and control groups. Study patients were less likely to be diagnosed with preterm labor (PTL) than controls (45.7% versus 70.8%, respectively; P < 0.001). The incidence of preterm premature rupture of membranes was similar between the groups (8.6% versus 8.1%; P = 0.770). We concluded that the incidence of recurrent SPTD was similar in women with cerclage treated with 17P or ONS, although women receiving 17P had a lower incidence of PTL. This benefit of 17P should be considered when managing patients with prior SPTD and cerclage.

Prophylaxis with 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery: does gestational age at initiation of treatment matter?

OBJECTIVE: The purpose of this study was to determine effectiveness of 17 alpha-hydroxyprogesterone caproate (17 P) prophylaxis by gestational age (GA) at 17 P initiation. STUDY DESIGN: Singleton gestations with > or = 1 preterm birth (PTB) treated with 17 P prophylaxis for recurrent preterm birth before 27 weeks were identified from a data base. Data were stratified by GA at 17 P initiation (16-20.9 [n = 599] weeks and 21-26.9 [n = 307] weeks) and number of PTB (1, 2, > 2). Outcome variables were PTB at < 37, < 35, and < 32 weeks. RESULTS: No significant differences were found in gestational age at delivery or rates of recurrent PTB < 37, < 35, and < 32 weeks between those women initiating 17 P at 16-20.9 weeks or 21-26.9 weeks, or when stratified by number of prior preterm deliveries. CONCLUSION: Initiation of 17 P prophylaxis at 21-26.9 weeks is as effective as initiation at 16-20.9 weeks of gestation.