Precocious cervical ripening as a screening target to predict spontaneous preterm delivery among asymptomatic singleton pregnancies: a systematic review.

Routine second-trimester transvaginal ultrasonographic (TVU) screening for short cervical length (CL) predicts spontaneous preterm delivery (SPTD), albeit with limited sensitivity (35-40%) and a moderate positive likelihood ratio of 4-6. However, CL describes one of the multidimensional changes that are associated with precocious cervical ripening (PCCR) and that also include cervical softening, cervical funneling (CF), and dilation. PCCR, a precursor and a strong predictor for SPTD, was proposed as a potential screening target. We hypothesized that screening for composite measures of PCCR (eg, CL, CF, cervical consistency, and dilation) with the use of either digital examination or TVU would improve the prediction of SPTD compared with screening for short CL alone. We searched PubMed and EMBASE electronic databases for observational cohort studies to evaluate cervical screening in asymptomatic obstetric populations. Multidimensional composite cervical measures were assessed in 10 datasets (n = 22,050 pregnancies) and 12 publications. Appreciable heterogeneity in cervical measurements, data quality, and outcomes across studies prevented quantitative metaanalysis. Only one study reported intra- and interobserver reliability of cervical measurements. The prevalence of CF ranged from 0.7-9.1%. Five studies compared composite measures of PCCR (ie, CL and CF) with short CL alone and consistently reported improved screening performance. Among 3 TVU studies, gains in sensitivity ranged from 5-27%, and increases in positive likelihood ratio ranged from 3-16. Our findings suggest that composite measures of PCCR might serve as valuable screening targets. High-quality interdisciplinary studies that integrate epidemiologic approaches are needed to test this hypothesis and to accelerate the translation of advances in cervical pathophysiology into effective preventive interventions.

Cervical intraepithelial neoplasia and cancer in women 35 years and older.

OBJECTIVE: To evaluate the distribution of abnormal cytohistopathology among low-income women 35 years and older compared with women younger than 35 years. MATERIALS AND METHODS: This was a retrospective analysis of the 896 women who presented to the dysplasia clinic at an urban, public, tertiary care hospital with abnormal cervical cytology from September 23, 2008, to September 23, 2010. Statistical comparisons were made using t, χ(2), and Wilcoxon rank sum tests. RESULTS: Of the 896 patients, 460 (51%) were aged 35 years or older. Among the women 35 years and older, 56% had negative/benign histologic findings compared with 45% in women younger than 35 years. Conversely, women 35 years and older had lower rates of cervical intraepithelial neoplasia 1 (14%) than women younger than 35 years (30%). However, the prevalence of cancer diagnosis, per colposcopy, increased significantly with age, affecting 6% of women aged 50 years or older, 2% of women aged 35 to 49 years, and 1% of women younger than 35 years (p = .0008). CONCLUSIONS: Women older than 35 years with abnormal cytology demonstrated increased severity of cervical intraepithelial neoplasia on histology compared with younger women. Although women younger than 35 years were more likely to have transient human papillomavirus infections, a very high prevalence of severe cervical intraepithelial neoplasia and cancer was identified among women aged 35 years and older. Careful evaluation and follow-up must be performed for this group of women who may have previously been considered by some clinicians to be low risk on the basis of their age.

Cigarette smoking and fetal morbidity outcomes in a large cohort of HIV-infected mothers.

BACKGROUND: Reproductive-age women comprise approximately 25% of all persons living with HIV/AIDS in the United States. HIV infection and smoking during pregnancy are independent risk factors for adverse fetal outcomes. We examined predictors of fetal growth restriction among infants born to HIV-infected mothers who smoke cigarettes in pregnancy. METHODS: We analyzed hospital discharge data linked to birth records from the state of Florida for 1998-2007 (N = 1,645,209). The outcomes of interest included: low and very low birth weight (LBW and VLBW), preterm and very preterm birth (PTB and VPTB), and small for gestational age (SGA). We calculated adjusted rate ratios (ARR) for these outcomes by HIV/AIDS status, smoking status, and sociodemographic variables. We also examined the association between the observed fetal morbidity outcomes and the interaction between HIV/AIDS and smoking status. We employed the generalized estimating equation framework to correct for intracluster correlations. RESULTS: All fetal morbidity outcomes were more common in mothers who had HIV/AIDS, regardless of smoking status. Maternal HIV status and cigarette use were independent predictors of LBW, PTB, and SGA, with morbidity effects more prominent in HIV-infected mothers who smoke cigarettes. We observed a significant interaction between maternal HIV and smoking status, in which mothers who were HIV positive and smoked during pregnancy experienced the greatest risks for LBW (ARR = 2.24 [1.89-2.65]), SGA (ARR = 1.95 [1.67-2.29]), and PTB (ARR = 1.70 [1.42-2.03]). CONCLUSIONS: HIV-infected mothers who smoke cigarettes during pregnancy have a heightened risk for adverse fetal morbidity outcomes. There is a need for integration of smoking cessation interventions into ongoing HIV/AIDS programs.

A Time-motion Comparison of Itemized Treatment Costs in First and Second In Vitro Fertilization Attempts: A United Kingdom Fertility Centre Experience.

Objective: To assess the difference in cost between initial and second in vitro fertilization (IVF) cycles in the United Kingdom. Methods: This prospective time-motion analysis captured data on average time spent on 31 representative components of the IVF sequence as provided by clinical team members in seven categories. Audits of consumables and observations on personnel costs were made from total of 120 fertility patients undergoing initial or second IVF cycles (n=736) between 1 January 2002 and 31 December 2002 at a UK assisted fertility unit. Results: Patients spent an average of 16.71±4.3 hrs with staff during an initial IVF cycle, resulting in direct personnel costs of £577.05±151.01. When consumables were included, each initial cycle cost the clinic approximately £2246.57±151.01. For second IVF cycles, patients spent significantly less time with staff compared to their first IVF cycle (6.94±2.44 hrs; p<0.05), corresponding to £257.53±90.77 in personnel cost. Conclusions: This is the first economic appraisal of the IVF treatment sequence in the UK using a timemotion analysis model. Our study found that when combined with consumables, total institutional costs for second IVF cycles were significantly reduced when compared to initial cycles (£1813.12±90.77; p<0.05). Aggregating data from all IVF cycles performed within the fertility centre during the study interval, initial cycles were found to be front-loaded, resulting in £252,420 more in institutional costs as compared with subsequent IVF cycles. While these observations were registered in 2003, an inflation adjustment using recent European Commission Eurostat data for healthcare finds the difference between initial and subsequent fresh IVF cycles in present currency to be approximately £579.14 per cycle. Time-motion analysis can identify episodes of care that can be streamlined to improve outcomes and reduce cost.

Detection of alcohol use in the second trimester among low-income pregnant women in the prenatal care settings in Jefferson County, Alabama.

BACKGROUND: Prenatal alcohol use, a leading preventable cause of birth defects and developmental disabilities, remains a prevalent public health concern in the United States. This study aims to detect the proportion and correlates of prenatal alcohol use in the prenatal care settings in Alabama. Prenatal care settings were chosen because of their potential as stable locations to screen for and to reduce prenatal alcohol use within a community. METHODS: We conducted a cross-sectional study of 3,046 women in the 22 and 23 weeks of gestation who sought prenatal care in 8 community-based public clinics and participated in the Perinatal Emphasis Research Center project in Jefferson County, Alabama, from 1997 to 2001. Frequency and quantity of alcohol use in the past 3 months were assessed by research nurses during face-to-face interviews. We conducted logistic regression analyses to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of correlates of prenatal alcohol use. RESULTS: Participants were predominantly young, African American, and unmarried, 86.5% on Medicaid. The proportion of alcohol use in the second trimester of pregnancy was 5.1%; 0.3% of women reported 4 or more drinks on a drinking day to research nurses. Older maternal age (OR = 1.11; 95% CI = 1.08 to 1.15), use of welfare (OR = 1.43; 95% CI = 1.02 to 2.02), and male partner-perpetrated violence (OR = 2.96; 95% CI = 1.92 to 4.56) were positively associated with elevated risk of prenatal alcohol use. Protective factors included higher levels of self-esteem (OR = 0.94; 95% CI = 0.89 to 0.98) and more years of education (OR = 0.88; 95% CI = 0.78 to 0.98). CONCLUSIONS: Prenatal alcohol use remains a public health issue among low-income pregnant women in Jefferson County, Alabama. Research nurses detected it in the second trimester. Future studies need to encourage screening for prenatal alcohol use in the prenatal care settings by obstetrician-gynecologists, family physicians, nurses, and midwives. Combined interventions to educate and empower women and strengthen families are needed.

Male subfertility and the role of micronutrient supplementation: clinical and economic issues.

The concept of male subfertility has evolved rapidly since 2000. This term is discussed based upon evidence relating to its first entrance into the literature, along with contemporary references to its purported incidence and prevalence. Factors affecting sperm quality are described in detail, and available data pertaining to the effects of micronutrients on spermatic parameters and resulting pregnancies are described. The first cost-efficiency analysis of the use of micronutrients vs. assisted reproductive technologies is presented. This paper also describes a therapeutic approach to males, recognizing that many potential fathers have no recourse to medical facilities to evaluate their fertility. At a time when medical dollars are either nonexistent or precious, such an approach using micronutrient supplementation may be cost-effective in developing and possibly even in developed countries.

Prediction of individual probabilities of livebirth and multiple birth events following in vitro fertilization (IVF): a new outcomes counselling tool for IVF providers and patients using HFEA metrics.

In vitro fertilization (IVF) has become a standard treatment for subfertility after it was demonstrated to be of value to humans in 1978. However, the introduction of IVF into mainstream clinical practice has been accompanied by concerns regarding the number of multiple gestations that it can produce, as multiple births present significant medical consequences to mothers and offspring. When considering IVF as a treatment modality, a balance must be set between the chance of having a live birth and the risk of having a multiple birth. As IVF is often a costly decision for patients-financially, medically, and emotionally-there is benefit from estimating a patient's specific chance that IVF could result in a birth as fertility treatment options are contemplated. Historically, a patient's "chance of success" with IVF has been approximated from institution-based statistics, rather than on the basis of any particular clinical parameter (except age). Furthermore, the likelihood of IVF resulting in a twin or triplet outcome must be acknowledged for each patient, given the known increased complications of multiple gestation and consequent increased risk of poor birth outcomes. In this research, we describe a multivariate risk assessment model that incorporates metrics adapted from a national 7.5-year sampling of the Human Fertilisation & Embryology Authority (HFEA) dataset (1991-1998) to predict reproductive outcome (including estimation of multiple birth) after IVF. To our knowledge, http://www.formyodds.com is the first Software-as-a-Service (SaaS) application to predict IVF outcome. The approach also includes a confirmation functionality, where clinicians can agree or disagree with the computer-generated outcome predictions. It is anticipated that the emergence of predictive tools will augment the reproductive endocrinology consultation, improve the medical informed consent process by tailoring the outcome assessment to each patient, and reduce the potential for adverse outcomes with IVF.

Folic acid and human reproduction-ten important issues for clinicians.

This article presents data on the current best evidence-based clinical practices and controversies surrounding folic acid supplementation/fortification for the prevention of neural tube defects (NTDs) during early pregnancy. Formatted as a series of ten clinical questions, answers and extensive discussion are provided for each point. We assess the history and evidence behind supplementation and fortification, racial/ethnic disparities in NTDs on a global scale, and present information on risk factors for NTDs other than dietary folic acid deficiency. Also discussed are public health challenges, including disparities in NTD rates, population-wide monitoring of NTDs, and tracking safety data in the post-fortification era. Emerging data are also reviewed regarding the role folic acid may play in malignant processes, cardiovascular disease, male fertility, and other medical conditions.

The differential association between education and infant mortality by nativity status of Chinese American mothers: a life-course perspective.

OBJECTIVES: Integrating evidence from demography and epidemiology, we investigated whether the association between maternal achieved status (education) and infant mortality differed by maternal place of origin (nativity) over the life course of Chinese Americans. METHODS: We conducted a population-based cohort study of singleton live births to US-resident Chinese American mothers using National Center for Health Statistics 1995 to 2000 linked live birth and infant death cohort files. We categorized mothers by nativity (US born [n = 15 040] or foreign born [n = 150 620]) and education (≥ 16 years, 13-15 years, or ≤ 12 years), forming 6 life-course trajectories. We performed Cox proportional hazards regressions of infant mortality. RESULTS: We found significant nativity-by-education interaction via stratified analyses and testing interaction terms (P < .03) and substantial differentials in infant mortality across divergent maternal life-course trajectories. Low education was more detrimental for the US born, with the highest risk among US-born mothers with 12 years or less of education (adjusted hazard ratio = 2.39; 95% confidence interval = 1.33, 4.27). CONCLUSIONS: Maternal nativity and education synergistically affect infant mortality among Chinese Americans, suggesting the importance of searching for potential mechanisms over the maternal life course and targeting identified high-risk groups and potential downward mobility.

A population based economic analysis of cross-border payments for fertility services in Luxembourg.

OBJECTIVE: How fertility patients utilise assisted reproductive services can depend on how easy it is to access such services locally. Little data exist to document the extent of economic outflow that accompanies cross-border patient travel specifically for medical procedures that cannot be obtained in country. METHODS: In this investigation, data from Luxembourg's social security agency were used to audit medical reimbursement payments for IVF within and outside the Grand Duchy of Luxembourg between 1998 and 2007. This study interval offered an opportunity to track IVF expenditures before and after IVF was made freely available within the Grand Duchy. RESULTS: Reimbursement authorizations to IVF providers outside Luxembourg remained stable or slightly elevated until 2005, two years after Luxembourg opened its first IVF centre. Once established in Luxembourg, annual utilisation of the domestic IVF service generally trended upwards (217 cycles in 2003 vs. 569 in 2008). Meanwhile, payments to foreign IVF clinics declined steadily after 2005 reflecting a diminishing number of Luxembourg patients seeking cross-border IVF treatment. CONCLUSION: These data represent the most comprehensive register of cross-border reproductive visits in Europe. Since Luxembourg fully reimburses its citizens for health-related expenses irrespective of where the medical service is obtained, the current investigation renders the "out of pocket" effect of IVF fees irrelevant and characterise consumption of elective medical treatments as a function of service site. Further studies are needed to determine if these findings will generalise to other geographic regions.

Perinatal outcomes among foreign-born and US-born Chinese Americans, 1995-2000.

This paper examines nativity differences in adverse perinatal outcomes of Chinese-American mothers. Singleton live births to US-resident Chinese women (150,620 foreign-born, 15,040 US-born) and a random sample of 150,620 non-Hispanic White mothers were selected from 1995 to 2000 national linked birth/infant death certificate files. Associations between maternal nativity status and adverse perinatal outcomes were assessed using multivariable logistic regressions. Compared to US-born Chinese mothers, foreign-born Chinese mothers were less likely to be unmarried, teen mothers, have a non-Hispanic White or other race partner, be rural residents, and more likely to be less educated, or utilize prenatal care inadequately. Controlling for these factors, foreign-born Chinese-American mothers had significantly lower risks for low birth weight, preterm birth, and small-for-gestational age, whereas risks for infant mortality, neonatal mortality, and post-neonatal mortality did not differ significantly from those of infants of US-born Chinese mothers. Chinese Americans exhibited clear nativity differentials for adverse birth outcomes.

Comparative study on the use of analytical software to identify the different stages of breast cancer using discrete temperature data.

Breast cancer is the second leading cause of death in women. It occurs when cells in the breast begin to grow out of control and invade nearby tissues or spread throughout the body. The limitations of mammography as a screening modality, especially in young women with denser breasts, necessitated the development of novel and more effective screening strategies with acceptable sensitivity and specificity. The aim of this study was to develop a feasible interpretive software system which was able to detect and classify breast cancer patients by employing techniques of different analytical software. The protocol described uses 6,000 pieces of thermal data collected from 16-sensors, eight placed on the surface of each breast. Data was collected every 5 min for the duration of the test period. Placement of sensors was accomplished with the use of a template design from information provided by the national tumor registry to insure that the information was collected in areas of the breast where most breast cancers develop. Data in this study was collected from 90 individuals exhibiting four different breast conditions, namely: normal, benign, cancer and suspected-cancer. The temperature data collected from these 16 sensors placed on the surface of each breast were fed as inputs to the classifiers. Comparisons were made on five different kinds of classifiers: back-propagation algorithm, probabilistic neural network, fuzzy (Sugeno-type), Gaussian mixture modeland support vector machine. These classifiers were able to attain approximately 80% accuracy in classifying the four different diagnoses (normal, benign, cancer and suspected-cancer). Gaussian mixture model was the most sensitive classifier, achieving the highest sensitivity of 94.8%. Support vector machine was considered the best classifier as it was able to produce the most specific and accurate results. Based on these evaluations, this current effort shows the feasibility of applying analytical software techniques together with the real-time functional thermal analysis to develop a potential tool for the detection and classification of breast cancer.

Hyperfertility, obesity, and stillbirth: new considerations for clinical practice.

This research focuses on two well known phenomenon that regularly confront obstetricians on a worldwide basis. The first is hyperfertility, whose effects are well known within and outside the obstetrics community. The second is obesity, a problem of growing importance throughout the developed and developing world. Each is discussed in view of recently published evidence. In this work, we show how these two concepts interlock and how they represent a substantial clinical challenge to all physicians providing care to reproductive aged women.

The association between maternal characteristics and different types and levels of discordance in triplet pregnancies.

OBJECTIVE: This study evaluated the association of maternal factors known to influence outcomes of triplets, different discordance levels (-25, 25.1-35, and )35%), and three types (according to the birth weight of the middle-sized triplet) of birth weight discordance in triplets. METHODS: We used data collected by the Women's Health Division of Matria Healthcare, Inc. (Marietta, GA). We analyzed a cohort of 2706 triplet sets, to calculate the frequencies of different levels and types of birth weight discordance by maternal age, parity, weight, height, body mass index and weight gain at 24 weeks of gestation. RESULTS: We found a positive association between maternal parity and birth weight discordance level but no clear association between the other maternal factors and the level of discordance as well as the type of discordance. However, a trend was seen whereby overweight women had a trend towards the low-skew (a set comprising one large and two small triplets) type of birth weight discordance and an opposite trend in underweight women. CONCLUSIONS: These results corroborate previous findings that nulliparity is associated with aberrant growth in triplet pregnancies.

The Istanbul international consensus statement on the perinatal care of multiple pregnancy.

The purpose of this document is to expand the 1995 ISTS/COMBO Declaration of Rights which was initially produced to promote awareness of the special needs of multiple birth infants, children, and adults. It addresses the clinical and ethical dimensions of perinatal care of multiple pregnancy. The ad hoc committee was chaired by Isaac Blickstein. The following individuals were present (in alphabetical order): Birgit Arabin (Zwolle, Netherlands/Berlin, Germany), Isaac Blickstein (Rehovot, Israel), Frank A. Chervenak (NY, USA), Zehra Nese Kavak (Istanbul, Turkey), Louis G. Keith (Chicago, USA), Eric S. Shinwell (Rehovot, Israel) and Yves Ville (Paris, France). Secretary of the meeting was Alin Basgul (Istanbul, Turkey). This statement was endorsed by the International Society of Twin Studies (Ghent, Belgium, June, 2007) and by the World Association of Perinatal Medicine (Florence, Italy, September, 2007).

On the possible cause of monozygotic twinning: lessons from the 9-banded armadillo and from assisted reproduction.

Available hypotheses proposed to explain the mechanism of zygotic splitting fail to explain why monozygotic twins are more prevalent after all methods of assisted reproduction and which structure is likely to control this phenomenon. Arguably, a small proportion of oocytes might have an inborn propensity to undergo splitting upon fertilization leading to the constant prevalence of spontaneous monozygotic conceptions among different populations. Ovarian stimulation would then predictably increase the number of available splitting-prone oocytes and consequently would increase the chance for such oocytes to develop into monozygotic twins, leading to a 'dose'-dependent relationship between monozygosity rates and the combined effect of infertility treatment. Embryonic division into 2 distinct cell lines begins and accommodates within an intact zona pellucida that controls the process by preventing ill-timed hatching. Human fertilized oocytes are able to undergo 2 binary fissions, just as is the case for the 9-banded armadillo (the only other mammal that produces monozygotic quadruplets) and to give rise to a variety of combinations of monozygotic pregnancies. This hypothetical explanation does not negate the already existing and genetically sound hypotheses, but places them into a broader perspective that respects recent observations from modern infertility treatment.

Impact of advanced maternal age on neonatal survival of twin small-for-gestational-age subtypes.

AIM: We examined the impact of advanced maternal age (>40 years old) on the survival of twin small-for-gestational-age (SGA) infants, that is, infants who were smaller in size than was expected for the baby's sex, genetic heritage, and gestational age. METHODS: The present study was a retrospective cohort study on twin live births in the USA from 1995 to 1998 inclusive. Two categories of SGA babies were defined: discordant (when only one of a twin pair was SGA) and concordant (when both were SGA). Otherwise, the twin pair was appropriate-for-gestational-age (AGA) concordant. RESULTS: 192,195 twin pairs were analyzed. The incidence of SGA discordance and concordance was 11.8% and 3.9%, respectively. The occurrence of both SGA subtypes tended to decrease with increasing maternal age. The unadjusted risk for neonatal mortality increased when both twins were affected (15.8: 22.8 and 56.6 per 1000 among AGA concordant, SGA discordant and SGA concordant twins; P-value for trend < 0.0001). Using maternal-age-specific AGA babies as reference, the adjusted risk for neonatal mortality climbed progressively with advancing maternal age in a dose-dependent pattern, being lowest among teenagers and highest in mothers aged > or =40 years. CONCLUSIONS: SGA discordance and concordance declined with advancing maternal age. In contrast, neonatal mortality of both SGA subtypes worsened with the increase in maternal age compared with that of the age-specific AGA infants. These findings are potentially useful to care providers in counseling older women, a group that is progressively increasing in size and is most susceptible to twining.

Comparison between singleton- and triplet-specific "growth" curves to detect growth restricted triplet infants.

OBJECTIVE: To evaluate whether triplet- or singleton-specific growth standards should be used to define the growth restricted triplet fetus/neonate. STUDY DESIGN: We retrospectively compared the predictive values of singleton vs. triplet-specific "growth" standards using the neonatal ponderal index as reference for growth restriction. RESULTS: A ponderal index <1 SD from the mean was found in 356 (14.4%) of 2477 triplet infants. A total of 686 (27.7%) infants were small for gestational age (SGA) by singleton standards, but only 168 (6.8%) by triplet standards. After 31 weeks' gestation, triplet standards are significantly better associated with a low ponderal index (OR 2.0, 95% CI 1.1, 3.4 at 32 weeks to OR 4.1, 95% CI 2.8, 6.3 at 36-37 weeks), resulting in better positive predictive value and higher specificity of triplet standards in predicting a low ponderal index. CONCLUSION: Triplet birth weight standards are better than singleton standards at >31 but not at < or =31 weeks' gestation in predicting a low neonatal ponderal index.

Slow change in body mass index during early triplet pregnancy is associated with decreased birth weight.

OBJECTIVE: This study evaluates the impact of an average change in body mass index (BMI) during the first 16-25 weeks on outcomes of triplet pregnancies. STUDY DESIGN: In this retrospective observational study we evaluated a cohort of triplets born to 1235 nulliparas and 705 multiparas. The difference between the pregravid body mass index (BMI) and that obtained upon admission at 16-25 weeks' gestation was averaged to obtain the weekly change in BMI, defined as slow, typical, or fast by values<1SD, +/-1SD, and >1SD from the mean average weekly change in BMI. We compared gestational age and birth weight parameters in these three subgroups and by parity. RESULTS: The average weekly BMI-adjusted weight gain was 0.18+/-0.08 and 0.17+/-0.08 kg/m2/week for nulliparas and multiparas, respectively. In both parity groups, differences were noted between slow and typical and between slow and fast, but not between typical and fast weight gain. Nulliparas with slow weight gain had a significantly higher incidence of infants weighing<1000 g (OR 2.0-2.5), 1000-1500 g (OR 1.4 compared with fast weight gain), and included 60-100% more sets with at least 1 SGA infant. In multiparas, there was no effect on gestational age, but otherwise, a similar trend for birth weight parameters was found. CONCLUSION: Slow weekly change in BMI (<1 SD from the mean) at 16-25 weeks is associated with decreased birth weight but there was no advantage for fast over a typical weigh gain.