Impact of the roll out of comprehensive emergency obstetric care on institutional birth rate in rural Nepal.

BACKGROUND: Increasing institutional births rates and improving access to comprehensive emergency obstetric care are central strategies for reducing maternal and neonatal deaths globally. While some studies show women consider service availability when determining where to deliver, the dynamics of how and why institutional birth rates change as comprehensive emergency obstetric care availability increases are unclear. METHODS: In this pre-post intervention study, we surveyed two exhaustive samples of postpartum women before and after comprehensive emergency obstetric care implementation at a hospital in rural Nepal. We developed a logistic regression model of institutional birth factors through manual backward selection of all significant covariates within and across periods. Qualitatively, we analyzed birth stories through immersion crystallization. RESULTS: Institutional birth rates increased after comprehensive emergency obstetric care implementation (from 30 to 77%, OR 7.7) at both hospital (OR 2.5) and low-level facilities (OR 4.6, p < 0.01 for all). The logistic regression indicated that comprehensive emergency obstetric care availability (OR 5.6), belief that the hospital is the safest birth location (OR 44.8), safety prioritization in decision-making (OR 7.7), and higher income (OR 1.1) predict institutional birth (p ≤ 0.01 for all). Qualitative analysis revealed comprehensive emergency obstetric care awareness, increased social expectation for institutional birth, and birth planning as important factors. CONCLUSION: Comprehensive emergency obstetric care expansion appears to have generated significant demand for institutional births through increased safety perceptions and birth planning. Increasing comprehensive emergency obstetric care availability increases birth safety, but it may also be a mechanism for increasing the institutional birth rate in areas of under-utilization.

Determinants of institutional birth among women in rural Nepal: a mixed-methods cross-sectional study.

BACKGROUND: Encouraging institutional birth is an important component of reducing maternal mortality in low-resource settings. This study aims to identify and understand the determinants of persistently low institutional birth in rural Nepal, with the goal of informing future interventions to reduce high rates of maternal mortality. METHODS: Postpartum women giving birth in the catchment area population of a district-level hospital in the Far-Western Development Region of Nepal were invited to complete a cross-sectional survey in 2012 about their recent birth experience. Quantitative and qualitative methods were used to determine the institutional birth rate, social and demographic predictors of institutional birth, and barriers to institutional birth. RESULTS: The institutional birth rate for the hospital's catchment area population was calculated to be 0.30 (54 home births, 23 facility births). Institutional birth was more likely as age decreased (ORs in the range of 0.20-0.28) and as income increased (ORs in the range of 1.38-1.45). Institutional birth among women who owned land was less likely (OR = 0.82 [0.71, 0.92]). Ninety percent of participants in the institutional birth group identified safety and good care as the most important factors determining location of birth, whereas 60 % of participants in the home birth group reported distance from hospital as a key determinant of location of birth. Qualitative analysis elucidated the importance of social support, financial resources, birth planning, awareness of services, perception of safety, and referral capacity in achieving an institutional birth. CONCLUSION: Age, income, and land ownership, but not patient preference, were key predictors of institutional birth. Most women believed that birth at the hospital was safer regardless of where they gave birth. Future interventions to increase rates of institutional birth should address structural barriers including differences in socioeconomic status, social support, transportation resources, and birth preparedness.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

OBJECTIVES: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 µg/24 h over the first year [total content 13.5 mg]) and a 30 µg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. METHODS: Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. RESULTS: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. CONCLUSIONS: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

Tuboovarian abscess. Factors associated with operative intervention after failed antibiotic therapy.

OBJECTIVE: To evaluate whether size of tuboovarian abscess (TOA) and other clinical characteristics were associated with the need for surgical intervention. STUDY DESIGN: A retrospective chart review of patients hospitalized at an inner city hospital between January 1998 and December 2007 with the diagnosis of TOA. Demographics, medical history, clinical markers of infection, radiology, pathology, and operative reports were examined. Student's t test and Fisher's exact test were utilized to analyze differences between groups. Multiple logistic regression analysis was performed to identify significant predictors of surgery. Receiver operating characteristic (ROC) analysis was used to assess how well TOA size and other significant variables were associated with the need for operative or procedural intervention. RESULTS: A total of 163 patients with TOA were identified; 41 patients were excluded based on specific criteria. Of the remaining 122 women, 65.6% responded to antibiotic therapy, and 34.4% had surgery or ultrasound-guided drainage. Mean TOA size in the medical group was 4.4 cm as compared to 7.3 cm in the surgical group (p < 0.0001). Maximal leukocyte count, older age, and parity were associated with significantly higher risk of surgery. The significant univariate variables remained significant after multivariate analysis. ROC curve analysis revealed an excellent discrimination of the need for surgical treatment as predicted by TOA size, with increased likelihood of surgical or procedural intervention with increasing TOA size. CONCLUSION: Radiographic size, leukocyte count, age, and parity are associated with operative or procedural treatment of tuboovarian abscess.

Cervical obstruction complicating second-trimester abortion: treatment with misoprostol.

BACKGROUND: Cervical cone biopsy or loop electrosurgical excision procedures (LEEP) may lead to cervical scarring, agglutination, or stenosis. Leiomyomas may also obstruct the lower uterine segment such that instruments cannot be passed from the vagina to the gestation. CASE: Two women requested second trimester abortion. Both women had undergone cervical LEEP. In addition, one woman had a 10-cm leiomyoma, which seemed to be obstructing the lower segment. In both, the external cervical os was essentially obliterated. After administration of misoprostol, the cervix softened markedly in 18-24 hours. In both women, the cervix dilated readily and allowed dilation and evacuation of the uterus. CONCLUSION: Misoprostol resulted in the ability to evacuate the uterus vaginally, in a situation that might have otherwise resulted in hysterotomy.

Relationship of obesity to outcome of medical abortion.

OBJECTIVE: The purpose of this study was to compare the outcome of medical abortion for obese women and nonobese women. STUDY DESIGN: We conducted a chart review of women having medical abortions in 2005-2007. Outcomes were classified as surgical intervention, need for additional visits, and complete abortion. The rate of surgical intervention was compared for women with BMI less than 30 to women with BMI greater than 30. RESULTS: Of the 1202 eligible procedures using mifepristone and misoprostol, there were 861 women with BMI less than 30 and 341 women with BMI greater than 30. Women with BMI less than 30, and women with BMI greater than 30 had identical rates of surgical intervention, 5% and 6%, respectively (P = .72). CONCLUSION: In light of the additional risks of surgical abortion to obese women, medical abortion should be considered for these women.

Mifepristone and misoprostol compared to osmotic dilators for cervical preparation prior to surgical abortion at 15-18 weeks' gestation: a randomised controlled non-inferiority trial.

OBJECTIVE: Cervical preparation is recommended prior to second-trimester surgical abortion. Osmotic dilators are an effective means to prepare the cervix, but require an additional procedure and may cause discomfort. We compared cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators. STUDY DESIGN: A randomised, controlled, non-inferiority trial was performed to compare cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators in women undergoing surgical abortion between 15 and 18 weeks gestation. The medication group (n=29) received mifepristone 200 mg orally 24 hours prior to uterine evacuation and misoprostol 400 µg buccally 2 hours before the procedure. The dilator group (n=20) underwent osmotic dilator insertion 24 hours prior to the procedure. The primary outcome was total procedure time, from insertion to removal of the speculum. Secondary outcomes included operative time (from intrauterine instrumentation to speculum removal), initial cervical dilation, nausea, pain, ease of procedure, and whether participants would choose the same modality in the future. RESULTS: For mean total procedure time, medication preparation (14.0 min, 95% CI 12.0-16.1) was not inferior to dilators (14.3 min, 95% CI 11.7 to 16.8, p<0.001). Mean operative time and ease of procedure were also similar between groups. More women in the medication group than the dilator group would prefer to use the same method in the future (86% vs 30%, p=0.003). CONCLUSION: Prior to surgical abortion at 15-18 weeks, use of mifepristone and misoprostol did not result in longer procedure times than overnight osmotic dilators. TRIAL REGISTRATION NUMBER: NCT01462.

Multicenter comparison of the contraceptive ring and patch: a randomized controlled trial.

OBJECTIVE: To understand if the contraceptive ring or patch was more acceptable, as measured primarily by continuation, to women using an oral contraceptive and interested in a nondaily, combined hormonal contraceptive. METHODS: Five hundred women were randomly assigned to use the contraceptive ring (n=249) or contraceptive patch (n=251) for four consecutive menstrual cycles, starting with their next menses. Participants returned for a single follow-up visit during the fourth cycle for an evaluation, which included a questionnaire to assess acceptability and adverse effects. RESULTS: Rates of completion of three cycles were 94.6% (95% confidence interval [CI] 91.0-97.1%) and 88.2% (95% CI 83.4-92.0%) for ring and patch users, respectively (P=.03). Of these women, 71.0% (95% CI 64.8-76.6%) and 26.5% (95% CI 21.0-32.6%), respectively, planned to continue their method after the study (P<.001). Women switching to the patch were significantly more likely than women switching to the ring to experience longer periods (38% compared with 9%), increased dysmenorrhea (29% compared with 16%), frequent nausea (8% compared with 1%), frequent mood swings (14% compared with 8%), and frequent skin rash (12% compared with 2%) and were less likely to experience frequent vaginal discharge (8% compared with 17%). Ring users preferred the ring to the oral contraceptive (P<.001), and patch users preferred the oral contraceptive to the patch (P<.001). Nugent scores increased only in patch users (P=.01), although most of these women were asymptomatic. CONCLUSION: Women satisfied with combined oral contraceptives and interested in a nondaily method are more likely to continue using the contraceptive ring than the contraceptive patch. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00269620. LEVEL OF EVIDENCE: I.

Mifepristone in second-trimester medical abortion: a randomized controlled trial.

OBJECTIVE: To investigate the adjunctive use of mifepristone in second-trimester induction abortions using misoprostol 1 day after feticidal digoxin. METHODS: This is a randomized, placebo-controlled, double-blind trial of mifepristone in second-trimester induction termination using misoprostol after feticidal digoxin. Women seeking abortion between 18 and 23 weeks of gestation were offered enrollment. At the time of digoxin amnioinfusion, participants received a randomly allocated, identical-appearing capsule containing either mifepristone, 200 mg, or placebo. Patients returned the following day for induction with buccal misoprostol. The primary outcome was the time interval from the first misoprostol dose to abortion. Analysis utilized survival curves with log-rank testing. RESULTS: Of 64 women, 32 received mifepristone and 32 received placebo. The groups did not differ by ethnicity, age, parity, reason for termination, or gestational age. Median procedure time was significantly shorter for those who received mifepristone, 10 hours (95% confidence interval [CI] 8-12), than those who did not, 18 hours (95% CI 15-22), P<.01, and those parous, 10 hours (95% CI 9-14), compared with nulliparous, 16 hours (95% CI 12-22, P=.02). Other findings in the mifepristone compared with placebo group included rates of placental retention, 3.1% compared with 6.3% (P=.61), length of hospitalization, 0.66 days compared with 0.8 days (P=.23), and analgesic requirements, 27.2 mg compared with 39.3 mg morphine (P=.22). Side effects during induction were similar between groups. CONCLUSION: Addition of mifepristone in second-trimester termination inductions using misoprostol significantly reduces the abortion time interval. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00382538 LEVEL OF EVIDENCE: I.

Intervention rates for placental removal following induction abortion with misoprostol.

BACKGROUND: Second-trimester terminations can be performed via surgical or medical methods. It is essential to have the ability to safely and effectively perform induction terminations to offer a full range of services. Many studies of induction abortions report routine operative removal of the placenta after a set time period resulting in high rates of operative procedures. STUDY DESIGN: A retrospective chart review was performed for 233 women who underwent second-trimester induction abortions between November 2003 and November 2006. All women received intraamniotic injection of digoxin for feticide 1 day prior to induction. All inductions were performed using a schedule of 400 mcg of misoprostol initially followed by 200 mcg every 6 h for a maximum of 48 h. There were three methods of administering misoprostol: (1) vaginal administration for all doses, (2) vaginal and buccal used in combination and (3) buccal for all doses. Spontaneous expulsion of the placenta was expected. Operative intervention was performed for excessive bleeding or to expedite hospital discharge after a minimum of 4 h. No manual removal of placenta was done. RESULTS: The rate of operative intervention for retained placentas was 6% (14/233). Most (11/14) of the patients who underwent operative extraction for retained placentas did so to expedite discharge from the hospital. Overall, expectant management to allow spontaneous expulsion of the placenta for at least 4 h was not associated with serious morbidity. CONCLUSIONS: Our regimen of digoxin and misoprostol with a policy of expectant management of placental passage is associated with a very low rate of instrumented removal of the placenta. In the absence of bleeding, patients may be afforded intervals to at least 4 h for spontaneous expulsion of the placenta after fetal expulsion.

Study design to evaluate the safety and effectiveness of hormonal contraception for women.

A discussion of the issues that affect the study design of hormonal contraception is presented, including ethical issues, measurement of contraceptive efficacy. Observational studies, experimental studies, and meta-analysis in hormonal contraception are also reviewed.

Applications for Research Concerning Fetal or Placental Tissue and Expected Institutional Review Board Responses.

Proposals for research concerning fetal and/or placental tissue may be refused institutional review board (IRB) review, effectively preventing the research from occurring. We conducted an anonymous electronic survey of IRB chairs to determine their assessment of the likely response to research projects using fetal/placental tissue obtained from various procedures. We found that proposals concerning tissue obtained from diagnostic procedures or miscarriage were anticipated to be considered at most institutions. Tissue obtained after abortion was likely to be refused consideration by more than 25% of respondents. Additional consultation during review was anticipated for up to 30% of scenarios. Responses for fetal and placental tissue were similar. The most frequently anticipated reason for refusal was institutional policy.

Simultaneous very low dose mifepristone and vaginal misoprostol for medical abortion.

OBJECTIVE: This pilot study was designed to evaluate the outcome of medical abortion following simultaneous mifepristone (100 mg) and misoprostol (800 microg). METHODS: Enrollees had gestational ages up to 56 days and desired a medical abortion. They received 100 mg of mifepristone orally and 800 microg of misoprostol vaginally. Follow-up examination occurred in 2-7 days. A phone call 3 weeks later assessed symptoms and acceptability. A 95% success rate, as seen in higher dose studies, gives a 95% confidence interval of 88-100% for 40 subjects. RESULTS: Forty women were enrolled; 39 women had follow-up visits. Completed medical abortion was confirmed for 35 (90%) of 39 women. Four women had uterine aspiration. Two patients required repeat misoprostol. Median time from medication to abortion was 7 h. Most women (92%) strongly preferred taking all medications in the clinic. CONCLUSIONS: The simultaneous administration of vaginal misoprostol with 100 mg of oral mifepristone had the outcome of completed abortion within the predicted confidence interval. In addition, simultaneous dosing was highly acceptable.

Bleeding after medication-induced termination of pregnancy with two dosing schedules of mifepristone and misoprostol.

OBJECTIVE: This study examines bleeding pattern following medication-induced termination of pregnancy, comparing two different dosing schedules of mifepristone and misoprostol. STUDY DESIGN: Diary information was analyzed from a randomized, multicenter trial in which women used vaginal misoprostol 800 mug either 6-8 or 24 h following 200 mg of oral mifepristone. PARTICIPANTS AND METHODS: One thousand eighty women with pregnancies up to 63 days' gestation were recruited for the study; 540 were randomized to the 6- to 8-h dosing schedule, and 540 were randomized to the 24-h dosing schedule. Subjects recorded daily bleeding in a diary over 5 weeks. RESULTS: Total duration of bleeding ranged from 1 to 54 days, with a median of 7 days. Duration of spotting ranged from 1 to 80 days, with a median of 5 and 6 days (NS) in each of the two groups. Neither duration of bleeding nor duration of spotting were related to interval between mifepristone and misoprostol. Bleeding and spotting durations were not correlated with maternal age or smoking. Increased gestational age was correlated with longer bleeding and spotting times. Nulliparity was associated with longer bleeding time. CONCLUSION: Varying the interval between mifepristone and misoprostol in medication abortion does not affect duration or quantity of bleeding.

A randomized clinical trial of the addition of laminaria to misoprostol and hypertonic saline for second-trimester induction abortion.

OBJECTIVE: To compare the outcomes of second-trimester induction abortion with misoprostol and hypertonic saline, with and without use of laminaria. METHOD: Fifty-eight women, between 17.5 and 22.5 weeks' gestation, were randomly assigned to receive or omit laminaria in conjunction with other procedures for induction abortion. All women received a fetocidal dose of 60 cc intra-amniotic hypertonic saline. If the woman was to receive laminaria, they were inserted next. This was followed by vaginal misoprostol 200 mug, which was repeated every 6 h. RESULT: Women with laminaria inserted before misoprostol administration had longer intervals from start of misoprostol to delivery of the fetus (induction times) than women without laminaria. Induction time was 14.4 vs. 11.4 h, respectively (p=.04, Wilcoxon rank sum test). Total misoprostol use was higher in the laminaria group, 628 mug (95% CI, 516-738) vs. 496 mug (95% CI, 419-573) (p=.05). Total analgesic use was also higher in the laminaria group, 41 mg of morphine (95% CI, 32-50) vs. 26 mg of morphine (95% CI, 18-32) (p=.02). CONCLUSION: Laminaria use, in conjunction with misoprostol and hypertonic saline, significantly prolongs induction time and increases narcotic analgesia usage.

Second-trimester postabortion care for ruptured membranes, fetal demise, and incomplete abortion.

BACKGROUND: Guidance for postabortion care (PAC) is established for the first trimester but limited in the second trimester. OBJECTIVES: To establish evidence-based recommendations for PAC in the second trimester. SEARCH STRATEGY: Medline, POPLINE, and the Cochrane Central Register of Controlled Trials were searched with terms related to second-trimester PAC, including fetal demise, ruptured membranes, and incomplete abortion. The reference lists of retrieved articles were also searched. SELECTION CRITERIA: Clinical trials and comparative studies of women presenting in the second trimester (12-28weeks) were included if more than 50% of participants met PAC criteria or if outcomes for PAC were analyzed separately. DATA COLLECTION AND ANALYSIS: Data were extracted from included studies. When interventions in at least two articles were comparable, a meta-analysis was performed. MAIN RESULTS: Overall, 17 studies of 1419 women met inclusion criteria. Misoprostol given vaginally, sublingually, or buccally was associated with shorter expulsion times than was oral misoprostol. Additionally, 200µg of misoprostol was more effective than lower doses. Pretreatment with mifepristone decreased expulsion time. Misoprostol was more effective than oxytocin. CONCLUSION: Misoprostol with or without mifepristone is an effective treatment for second-trimester PAC. The minimum misoprostol dose is 200µg vaginally, sublingually, or buccally every 6-12hours.

Administration of depot medroxyprogesterone acetate on the day of mifepristone for medical abortion: a pilot study.

OBJECTIVE: We sought to evaluate satisfaction with timing of administration and continuation rates of depot medroxyprogesterone (DMPA) when given on the initial visit for first-trimester medical abortion. STUDY DESIGN: In this pilot study, we administered DMPA within 15 min of mifepristone administration. Participants were followed up in the clinic 7 days after enrollment and were contacted at 14 days, 28 days and 3, 6, 9 and 12 months by telephone. We assessed satisfaction with contraception timing, DMPA continuation, bleeding patterns and abortion completion. RESULTS: Twenty women were enrolled. At 7-day follow-up, 18 of 19 contacted participants (94.7%) were satisfied with timing of DMPA administration. Ten of 19 participants (52.6%) discontinued DMPA after the first injection. At 1 year, 3 participants out of 19 were continuing DMPA (15.7%). The median number of bleeding days after abortion was 19. Three participants had medical abortion failure. In the first year after abortion, there were four known repeat pregnancies. CONCLUSIONS: The timing of initiation of DMPA on the initial visit for medical abortion is satisfactory to women, but its influence on medical abortion efficacy requires further study. Continuation rates for DMPA were low in our sample. IMPLICATIONS: This pilot study provides groundwork for future larger studies to assess initiation of the injectable contraceptive DMPA on the day of mifepristone for medical abortion, but low continuation rates of DMPA in our sample emphasize the importance of access to intrauterine devices and implants after abortion.

Circulating cell-free fetal nucleic acid analysis may be a novel marker of fetomaternal hemorrhage after elective first-trimester termination of pregnancy.

Analysis of cell-free fetal DNA (fDNA) and RNA in maternal plasma could be useful in the diagnosis and management of complications of pregnancy. In this review, we discuss our studies to investigate the potential of fetal nucleic acid measurement in maternal plasma as a marker of fetomaternal hemorrhage (FMH) after elective first-trimester termination of pregnancy (TOP). Using quantitative real-time PCR amplification of the DYS1 sequence, elevation of plasma fDNA levels after TOP was observed, especially in the late first trimester. This corresponds with the functional development of the placental vascular structure and fetal hematopoiesis. This Y sequence-based PCR amplification assay, however, limits the analysis to pregnant women carrying male fetuses. Therefore, we also developed a real-time quantitative reverse-transcriptase PCR assay of the gamma-globin transcript as a marker of fetal erythroid cells. Although plasma gamma-globin mRNA levels were decreased after TOP in many patients, an elevation was observed in some patients at greater than 9 weeks' gestation, which is consistent with the increase in plasma fDNA levels. Our data suggest that fetal hematopoietic cells contribute to the pool of fetal nucleic acids in the maternal circulation. Measurement of cell-free fetal nucleic acid levels in maternal plasma may have clinical application as a novel marker of FMH after 9 weeks of gestation.

Methods for induced abortion.

We describe present methods for induced abortion used in the United States. The most common procedure is first-trimester vacuum curettage. Analgesia is usually provided with a paracervical block and is not completely effective. Pretreatment with nonsteroidal analgesics and conscious sedation augment analgesia but only to a modest extent. Cervical dilation is accomplished with conventional tapered dilators, hygroscopic dilators, or misoprostol. Manual vacuum curettage is as safe and effective as the electric uterine aspirator for procedures through 10 weeks of gestation. Common complications and their management are presented. Early abortion with mifepristone/misoprostol combinations is replacing some surgical abortions. Two mifepristone/misoprostol regimens are used. The rare serious complications of medical abortion are described. Twelve percent of abortions are performed in the second trimester, the majority of these by dilation and evacuation (D&E) after laminaria dilation of the cervix. Uterine evacuation is accomplished with heavy ovum forceps augmented by 14-16 mm vacuum cannula systems. Cervical injection of dilute vasopressin reduces blood loss. Operative ultrasonography is reported to reduce perforation risk of D&E. Dilation and evacuation procedures have evolved to include intact D&E and combination methods for more advanced gestations. Vaginal misoprostol is as effective as dinoprostone for second-trimester labor-induction abortion and appears to be replacing older methods. Mifepristone/misoprostol combinations appear more effective than misoprostol alone. Uterine rupture has been reported in women with uterine scars with misoprostol abortion in the second trimester. Fetal intracardiac injection to reduce multiple pregnancies or selectively abort an anomalous twin is accepted therapy. Outcomes for the remaining pregnancy have improved with experience.

Inverse correlation between maternal weight and second trimester circulating cell-free fetal DNA levels.

OBJECTIVE: Clinical applications of the analysis of cell-free fetal DNA in maternal plasma and serum are expanding. However, use of fetal DNA during prenatal screening requires knowledge of variables that might affect its levels in the maternal circulation. We conducted this study to estimate the effect of selected demographic factors on fetal DNA levels in the first and second trimesters of pregnancy. METHODS: We developed a database that included fetal DNA levels and clinical information, such as maternal age, ethnicity, weight, and smoking history. We measured fetal DNA levels in maternal plasma and serum using real-time quantitative polymerase chain reaction amplification of a Y chromosome specific sequence. The fetal DNA data from fresh first trimester plasma and previously frozen second trimester serum samples were analyzed separately. Fetal DNA levels were adjusted according to gestational age and storage time and then analyzed in association with the demographic factors. RESULTS: In the first trimester group, no significant association between maternal age, weight, ethnic background, or smoking and plasma fetal DNA levels was observed. In the second trimester group, a significant inverse correlation between maternal weight and serum fetal DNA level was demonstrated (r = -0.26, P =.007). This was especially prominent when the mothers weighed more than 170 lb (P =.001). Maternal age, ethnicity, and smoking were not significantly associated with the second trimester serum fetal DNA levels. CONCLUSION: Fetal DNA levels are affected by maternal weight in the second trimester. A correction for this effect may be needed in larger-scale studies or for future clinical applications that measure cell-free fetal nucleic acids in maternal circulation.