Preterm birth, a leading cause of neonatal death, is more common in multiple births and thus there has being an increasing call for reducing multiple births in ART. However, few studies have compared risk factors for preterm births amongst ART and non-ART singleton birth mothers.
A population-based study of 393,450 mothers, including 12,105 (3.1%) ART mothers, with singleton gestations born between 2007 and 2009 in 5 of the 8 jurisdictions in Australia. Univariable and multivariable logistic regression models were conducted to evaluate socio-demographic, medical and pregnancy factors associated with preterm births in contrasting ART and non-ART mothers.
Ten percent of singleton births to ART mothers were preterm compared to 6.8% for non-ART mothers (P < 0.01). Compared with non-ART mothers, ART mothers were older (mean 34.0 vs 29.7 yr respectively), less socio-economically disadvantaged (12.4% in the lowest quintile vs 20.7%), less likely to be smokers (3.8% vs 19.4%), more likely to be first time mothers (primiparous 62.4% vs 40.5%), had more preexisting hypertension and complications during pregnancy. Irrespective of the mode of conception, preexisting medical and pregnancy complications of hypertension, diabetes and antepartum hemorrhages were consistently associated with preterm birth. In contrast, socio-demographic variables, namely young and old maternal age (<25 and >34), socioeconomic disadvantage (most disadvantaged quintile Odds Ratio (OR) 0.95, 95% Confidence Interval (CI): 0.77–1.17), smoking (OR 1.12, 95%CI: 0.79–1.61) and priminarity (OR 1.19, 95% CI: 1.05–1.35, AOR not significant) shown to be associated with elevated risk of preterm birth for non-ART mothers were not demonstrated for ART mothers, even after adjusting for potential confounders. Nonetheless, in multivariable analysis, the association between ART and the elevated risk for singleton preterm birth persisted after controlling for all included confounding medical, pregnancy and socio-economic factors (AOR 1.51, 95% CI: 1.42–1.61).
Preterm birth rate is approximately one-and-a-half-fold higher in ART mothers than non-ART mothers albeit for singleton births after controlling for confounding factors. However, ART mothers were less subject to the adverse influence from socio-demographic factors than non-ART mothers. This has implications for counselling prospective parents.
Assisted reproductive technology; Singleton; Preterm birth; In vitro fertilisation; Risk factor
The burden of mental and behavioural disorders in Australia has increased significantly over the last decade. The aim of the current study is to describe the hospital admission rates for mental illness over a 10-year period for primiparous mothers in the first year after birth.
This is an Australian population-based descriptive study with linked data from the New South Wales Midwives Data Collection and Admitted Patients Data Collection. The study population included primiparous mothers who gave birth between 1 January 2001 and 31 December 2010. All hospital admissions with a mental health diagnosis in the first year after birth were recorded.
There were 6,140 mothers (1.67%) admitted to hospital with a principal diagnosis of mental health in the first year after birth between 2001 and 2010 in New South Wales (7,884 admissions, 2.15%). The hospital admission rates increased significantly over time, particularly from 2005. The increase in hospital admissions was mainly attributed to the diagnoses of unipolar depression, adjustment disorders and anxiety disorders.
This study shows that hospital admissions for mothers with a mental health diagnosis after birth in New South Wales has significantly increased in the last decade. Possible reasons for this change need to be studied further.
Mental health; Increasing trend; Postpartum; Data linkage
Mental health conditions arising in the perinatal period, including depression, have the potential to impact negatively on not only the woman but also her partner, infant, and family. The capacity for routine, universal antenatal psychosocial assessment, and thus the potential for reduction of morbidity, is very significant.
To evaluate the impact of antenatal psychosocial assessment on perinatal mental health morbidity.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register, the Cochrane Depression, Anxiety and Neurosis Group’s Trials Register (CCDAN TR-Studies), HSRProj in the National Library of Medicine (USA), and the Current Controlled Trials website: http://www.controlled trials.com/ and the UK National Research Register (last searched March 2008).
Randomised and quasi-randomised controlled trials.
Data collection and analysis
At least two review authors independently assessed trials for eligibility; they also extracted data from included trials and assessed the trials for potential bias.
Two trials met criteria for an RCT of antenatal psychosocial assessment. One trial examined the impact of an antenatal tool (ALPHA) on clinician awareness of psychosocial risk, and the capacity of the antenatal ALPHA to predict women with elevated postnatal Edinburgh Depression Scale (EDS) scores, finding a trend towards increased clinician awareness of ‘high level’ psychosocial risk where the ALPHA intervention had been used (relative risk (RR) 4.61 95% confidence interval (CI) 0.99 to 21.39). No differences between groups were seen for numbers of women with antenatal EDS scores, a score of greater than 9 being identified by ALPHA as of concern for depression (RR 0.69 95% CI 0.35 to 1.38); 139 providers. The other trial reported no differences in EPS scores greater than 12 at 16 weeks postpartum between the intervention (communication about the EDS scores with the woman and her healthcare providers plus a patient information booklet) and the standard care groups (RR 0.86 95% CI 0.61 to 1.21; 371 women).
While the use of an antenatal psychosocial assessment may increase the clinician’s awareness of psychosocial risk, neither of these small studies provides sufficient evidence that routine antenatal psychosocial assessment by itself leads to improved perinatal mental health outcomes. Further studies with better sample size and statistical power are required to further explore this important public health issue. It will also be important to examine outcomes up to one year postpartum not only for mother, but also infant and family.
*Prenatal Care; Anxiety Disorders [*diagnosis; prevention & control]; Depression, Postpartum [*diagnosis; prevention & control]; Mental Health; Puerperal Disorders [*diagnosis; prevention & control; psychology]; Randomized Controlled Trials as Topic; Female; Humans; Pregnancy
Vasa praevia (VP) is an obstetric condition that is associated with significant perinatal mortality and morbidity. Although the incidence of VP is low, it is one of the few causes of perinatal death that can be potentially prevented through detection and appropriate care. The experience of women diagnosed with or suspected to have VP is largely unknown. The aim of this study was to explore the experiences and impact that a diagnosis or suspected diagnosis of VP had on a group of Australian women.
A qualitative study using a descriptive exploratory design was conducted and Australian women diagnosed with VP were recruited via online methods in 2012. An inductive approach was undertaken and interviews were analysed using the stages of thematic analysis.
Of the 14 women interviewed, 11 were diagnosed with VP during pregnancy with 5 subsequently found not to have VP (non-confirmed diagnosis). Three women were diagnosed during childbirth with one neonatal death. Five major themes were identified: feeling like a ticking time bomb; getting diagnosis right; being taken seriously; coping with inconsistent information; and, just a massive relief when it was all over.
This is the first study to describe women’s experience of being diagnosed with or suspected to have VP. The findings from this research reveal the dilemmas these women face even if their baby is ultimately born healthy. Their need for clear and consistent information, sensitive care, support and continuity is evident. Clinicians can use these findings in developing information, counselling and models of care for these women.
Vasa previa; Vasa praevia; Ultrasound; Qualitative research; Pregnancy; Obstetrics; Caesarean section
Studies from the United States and the United Kingdom have found that imprisoned women are less likely to experience poorer maternal and perinatal outcomes than other disadvantaged women. This population-based study used both community controls and women with a history of incarceration as a control group, to investigate whether imprisoned pregnant women in New South Wales, Australia, have improved maternal and perinatal outcomes.
Retrospective cohort study using probabilistic record linkage of routinely collected data from health and corrective services in New South Wales, Australia. Comparison of the maternal and perinatal outcomes of imprisoned pregnant women aged 18–44 years who gave birth between 2000–2006 with women who were (i) imprisoned at a time other than pregnancy, and (ii) community controls. Outcomes of interest: onset of labour, method of birth, pre-term birth, low birthweight, Apgar score, resuscitation, neonatal hospital admission, perinatal death.
Babies born to women who were imprisoned during pregnancy were significantly more likely to be born pre-term, have low birthweight, and be admitted to hospital, compared with community controls. Pregnant prisoners did not have significantly better outcomes than other similarly disadvantaged women (those with a history of imprisonment who were not imprisoned during pregnancy).
In contrast to the published literature, we found no evidence that contact with prison health services during pregnancy was a “therapunitive” intervention. We found no association between imprisonment during pregnancy and improved perinatal outcomes for imprisoned women or their neonates. A history of imprisonment remained the strongest predictor of poor perinatal outcomes, reflecting the relative health disadvantage experienced by this population of women.
Maternal morbidity; Perinatal outcome; Women in prison; Incarceration in pregnancy; Prison health care; Antenatal care; Substance use; Mental health disorder
Background: The effects of mental and behavioral disorders (MBD) due to substance use during peri-conception and pregnancy on perinatal outcomes are unclear. The adverse perinatal outcomes of primiparous mothers admitted to hospital with MBD due to substance use before and/or during pregnancy were investigated. Method: This study linked birth and hospital records in NSW, Australia. Subjects included primiparous mothers admitted to hospital for MBD due to use of alcohol, opioids or cannabinoids during peri-conception and pregnancy. Results: There were 304 primiparous mothers admitted to hospital for MBD due to alcohol use (MBDA), 306 for MBD due to opioids use (MBDO) and 497 for MBD due to cannabinoids (MBDC) between the 12 months peri-conception and the end of pregnancy. Primiparous mothers admitted to hospital for MBDA during pregnancy or during both peri-conception and pregnancy were significantly more likely to give birth to a baby of low birthweight (AOR = 4.03, 95%CI: 1.97–8.24 for pregnancy; AOR = 9.21, 95%CI: 3.76–22.57 both periods); preterm birth (AOR = 3.26, 95% CI: 1.52–6.97 for pregnancy; AOR = 4.06, 95%CI: 1.50–11.01 both periods) and admission to SCN or NICU (AOR = 2.42, 95%CI: 1.31–4.49 for pregnancy; AOR = 4.03, 95%CI: 1.72–9.44 both periods). Primiparous mothers admitted to hospital for MBDO, MBDC or a combined diagnosis were almost three times as likely to give birth to preterm babies compared to mothers without hospital admissions for psychiatric or substance use disorders. Babies whose mothers were admitted to hospital with MBDO before and/or during pregnancy were six times more likely to be admitted to SCN or NICU (AOR = 6.29, 95%CI: 4.62–8.57). Conclusion: Consumption of alcohol, opioids or cannabinoids during peri-conception or pregnancy significantly increased the risk of adverse perinatal outcomes.
pregnancy; perinatal outcomes; substance use; alcohol; opioids; cannabinoids
Background: Previous research showed that there was a significant increase in psychiatric hospital admission of postpartum mothers. The aim of the current study is to describe the length of hospital stays and patient days for mental and behavioural disorders (MBD) of new mothers in the first year after birth. Method: This was a cohort study based on linked population data between the New South Wales (NSW) Midwives Data Collection (MDC) and the NSW Admitted Patients Data Collection (APDC). The study population included primiparous mothers aged from 18 to 44 who gave birth between 1 July 2000 and 31 December 2005. The Kaplan–Meier method was used to describe the length of hospital stay for MBD. Results: For principal diagnoses of MBD, the entire length of hospital stay in the first year postpartum was 11.38 days (95% CI: 10.70–12.06) for mean and 6 days (95% CI: 5.87–6.13) for median. The length of hospital stay per admission was 8.47 days (95% CI: 8.03–8.90) for mean and 5 days (95% CI: 4.90–5.10) for median. There were 5,129 patient days of hospital stay per year for principal diagnoses of postpartum MBD in new mothers between 1 July 2000 and 31 December 2005 in NSW, Australia. Conclusions: MBD, especially unipolar depressions, adjustment disorders, acute psychotic episodes, and schizophrenia, or schizophrenia-like disorders during the first year after birth, placed a significant burden on hospital services due to long hospital stays and large number of admissions.
mental health; length of hospital stay; postpartum; data linkage
Worldwide, breastfeeding saves the lives of infants and reduces their disease burden. Breastfeeding also reduces the disease burden for mothers. This article examines who chooses to breastfeed and for how long in the American context. It also reviews the latest evidence about the consequences of breastfeeding for the health of both the infant and mother. The results of this review provide support for current national and international recommendations that support breastfeeding.
breastfeeding; lactation; postpartum weight retention; obesity; maternal health; infant health
There is a need to have uniformed reporting of perinatal mortality for births following assisted reproductive technology (ART) treatment to enable international comparison and benchmarking of ART practice.
The Australian and New Zealand Assisted Reproduction Database was used in this study. Births of ≥ 20 weeks gestation and/or ≥ 400 grams of birth weight following embryos transfer cycles in Australia and New Zealand during the period 2004 to 2008 were included. Differences in the mortality rates by different perinatal periods from a gestational age cutoff of ≥ 20, ≥ 22, ≥ 24, or ≥ 28 weeks (wks) to a neonatal period cutoff of either < 7 or < 28 days after birth were assessed. Crude and specific (number of embryos transferred and plurality) rates of perinatal mortality were calculated for selected gestational and neonatal periods.
When the perinatal period is defined as ≥ 20 wks gestation to < 28 days after birth, the perinatal mortality rate (PMR) was 16.1 per 1000 births (n = 630). A progressive contraction of the gestational age groups resulted in marked reductions in the PMR for deaths at < 28 days (22 wks 11.0; 24 wks 7.7; 28 wks 5.6); and similarly for deaths at < 7 days (20 wks 15.6, 22 wks 10.5; 24 wks 7.3; 28 wks 5.3). In contrast, a contraction of the perinatal period from < 28 to < 7 days after birth only marginally reduced the PMR from 16.2 to 15.6 per 1000 births which was consistent across all gestational ages.
The PMR for single embryo transfer (SET) births (≥ 20 weeks gestation to < 7 days post-birth) was significantly lower (12.8 per 1000 SET births) compared to double embryo transfer (DET) births (PMR 18.3 per 1000 DET births; p < 0.001, Fisher’s Exact Test). Similarly, the PMR for SET births (≥ 22 weeks gestation to < 7 days post-birth) was significantly lower (8.8 per 1000 SET births, p < 0.001, Fisher’s Exact Test) when compared to DET births (12.2 per 1000 DET births). The highest PMR (50.5 per 1000 SET births, 95% CI 36.5-64.5) was for twins following SET births (≥ 20 weeks gestation to < 7 days post-birth) compared to twins following DET (23.9 per 1000 DET births, 95% CI 20.8-27.1).
Reporting of perinatal mortality of ART births is an essential component of quality ART practice. This should include measures that monitor the impact on perinatal mortality of multiple embryo transfer. We recommend that reporting of perinatal deaths following ART treatment, should be stratified for three gestation-specific perinatal periods of ≥ 20, ≥ 22 and ≥ 28 completed weeks to < 7 days post-birth; and include plurality specific rates by SET and DET. This would provide a valuable international evidence-base of PMR for use in evaluating ART policy, practice and new research.
Perinatal mortality; Assisted reproductive technology treatment; Embryo transfer; Stillbirth; Neonatal mortality
To determine the rates of birth registration over a five-year period in New South Wales (NSW) and explore the factors associated with the rate of registration.
This is a cross-sectional study using linked population databases. The study population included all births of NSW residents in NSW between 2001 and 2005.
Birth registration rates in NSW were 82.66% in the year of birth, 93.19% in the first year, 94.02% in the second, 94.56% in the third and 95.08% in the fourth year after birth. The non-registration of births was mainly associated with such factors as neonatal and postneonatal death (adjusted OR = 3.84, 95% CI: 3.23-4.57); being Indigenous (adjusted OR = 3.26, 95% CI: 3.10-3.43); maternal age <25 or >39 years (adjusted OR = 2.81, 95% CI: 2.72-2.90); low birthweight (<2,500 grams) (adjusted OR = 1.79, 95% CI: 1.69-1.90); living in remote areas (adjusted OR = 1.57, 95% CI: 1.52-1.63); being born after the first quarter of year (adjusted OR = 1.08-1.56, 95% CI between 1.03-1.12 and 1.49-1.64); mother having more pregnancies (adjusted OR = 1.85-7.29, 95% CI between1.78-1.93 and 6.87-7.73). Mothers who were born overseas were more likely to register their births than those born in Australia (adjusted OR = 0.72, 95% CI: 0.69-0.75). Multiple births were more likely to be registered than singleton births (adjusted OR = 0.84, 95% CI: 0.76-0.92). About one-third of the non-registrations of births in NSW were explained by the risk factors. The reasons for the remaining non-registrations need to be investigated.
Of birth in NSW, 4.92% were not registered by the fourth year after birth.
Birth; Registration; Factor; Australia
In recent years there has been an increase in the use of population-based linked data. However, there is little literature that describes the method of linked data preparation. This paper describes the method for merging data, calculating the statistical variable (SV), recoding psychiatric diagnoses and summarizing hospital admissions for a perinatal psychiatric study.
The data preparation techniques described in this paper are based on linked birth data from the New South Wales (NSW) Midwives Data Collection (MDC), the Register of Congenital Conditions (RCC), the Admitted Patient Data Collection (APDC) and the Pharmaceutical Drugs of Addiction System (PHDAS).
The master dataset is the meaningfully linked data which include all or major study data collections. The master dataset can be used to improve the data quality, calculate the SV and can be tailored for different analyses. To identify hospital admissions in the periods before pregnancy, during pregnancy and after birth, a statistical variable of time interval (SVTI) needs to be calculated. The methods and SPSS syntax for building a master dataset, calculating the SVTI, recoding the principal diagnoses of mental illness and summarizing hospital admissions are described.
Linked data preparation, including building the master dataset and calculating the SV, can improve data quality and enhance data function.
Data preparation; Method; Psychiatric study; Australia
Amniotic fluid embolism (AFE) is a rare but severe complication of pregnancy. A recent systematic review highlighted apparent differences in the incidence, with studies estimating the incidence of AFE to be more than three times higher in North America than Europe. The aim of this study was to examine population-based regional or national data from five high-resource countries in order to investigate incidence, risk factors and outcomes of AFE and to investigate whether any variation identified could be ascribed to methodological differences between the studies.
We reviewed available data sources on the incidence of AFE in Australia, Canada, the Netherlands, the United Kingdom and the USA. Where information was available, the risk factors and outcomes of AFE were examined.
The reported incidence of AFE ranged from 1.9 cases per 100 000 maternities (UK) to 6.1 per 100 000 maternities (Australia). There was a clear distinction between rates estimated using different methodologies. The lowest estimated incidence rates were obtained through validated case identification (range 1.9-2.5 cases per 100 000 maternities); rates obtained from retrospective analysis of population discharge databases were significantly higher (range 5.5-6.1 per 100 000 admissions with delivery diagnosis). Older maternal age and induction of labour were consistently associated with AFE.
Recommendation 1: Comparisons of AFE incidence estimates should be restricted to studies using similar methodology. The recommended approaches would be either population-based database studies using additional criteria to exclude false positive cases, or tailored data collection using existing specific population-based systems.
Recommendation 2: Comparisons of AFE incidence between and within countries would be facilitated by development of an agreed case definition and an agreed set of criteria to minimise inclusion of false positive cases for database studies.
Recommendation 3: Groups conducting detailed population-based studies on AFE should develop an agreed strategy to allow combined analysis of data obtained using consistent methodologies in order to identify potentially modifiable risk factors.
Recommendation 4: Future specific studies on AFE should aim to collect information on management and longer-term outcomes for both mothers and infants in order to guide best practice, counselling and service planning.
The Indigenous population of Australia was estimated as 2.5% and under-reported. The aim of this study is to improve statistical ascertainment of Aboriginal women giving birth in New South Wales.
This study was based on linked birth data from the Midwives Data Collection (MDC) and the Registry of Births Deaths and Marriages (RBDM) of New South Wales (NSW). Data linkage was performed by the Centre for Health Record Linkage (CHeReL) for births in NSW for the period January 2001 to December 2005. The accuracy of maternal Aboriginal status in the MDC and RBDM was assessed by consistency, sensitivity and specificity. A new statistical variable, ASV, or Aboriginal Statistical Variable, was constructed based on Indigenous identification in both datasets. The ASV was assessed by comparing numbers and percentages of births to Aboriginal mothers with the estimates by capture-recapture analysis.
Maternal Aboriginal status was under-ascertained in both the MDC and RBDM. The ASV significantly increased ascertainment of Aboriginal women giving birth and decreased the number of missing cases. The proportion of births to Aboriginal mothers in the non-registered birth group was significantly higher than in the registered group.
Linking birth data collections is a feasible method to improve the statistical ascertainment of Aboriginal women giving birth in NSW. This has ramifications for the ascertainment of babies of Aboriginal mothers and the targeting of appropriate services in pregnancy and early childhood.
Birth; Aboriginality; data; Australia
After menarche, women have an increased prevalence of migraine compared to men. There is significant variability in the frequency and severity of migraine throughout the menstrual cycle. Women report migraines occur more frequently during menses, and that those are more severe than other migraines. This creates a unique challenge of effectively treating menstrually related and pure menstrual migraines. As with treatment of other migraines, both abortive and prophylactic treatment regimens are used. Triptans demonstrate efficacy in the abortive management of menstrually related and pure menstrual migraines. For migraines that occur primarily during menses or that are particularly resistant to other therapies, intermittent prophylactic therapies can be used. Naproxen and estrogens have been studied for this use. More recently, triptans have been examined and have shown efficacy for intermittent prophylaxis of menstrual migraine.
Menstrual migraine; Headache; Triptan; Abortive therapy; Prophylactic therapy; Intermittent prophylaxis
Studies using community-based breastfeeding counselors (CBBCs) have repeatedly shown positive impact on breastfeeding initiation, exclusivity and duration, particularly among low-income mothers. To date, there has not been a comprehensive study to determine the impact of CBBC attributes such as educational background and training, on the type of care that CBBCs provide.
This was a cross-sectional study of a convenience sample of CBBCs to ascertain the influence of counselor education and type of training on type of support and proficiency of CBBCs in communities across the United States. Invitations to participate in this online survey of CBBCs were e-mailed to program coordinators of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), La Leche League, and other community-based health organizations, who in turn invited and encouraged their CBBCs to participate. Descriptive analysis was used to describe participants (N = 847), while bivariate analysis using χ2 test was used to examine the differences between CBBC education, training received and breastfeeding support skills used. Multivariate logistic regression was used to assess the independent determinants of specific breastfeeding support skills.
The major findings from the research indicate that overall, educational attainment of CBBCs is not a significant predictor for the curriculum used in their training and type of support skills used during counseling sessions, but initial training duration was positively associated with the use of many breastfeeding support skills. Another major influence of counselor support to clients is the type of continuing education they receive after their initial training, with higher likelihood of use of desirable support skills associated with counselors continuing their breastfeeding education at conferences or trainings away from their job sites.
Our results show that different programs use different training curricula to train their CBBCs varying in duration and content. Counselor education is not a significant predictor of the type of training they receive. Continuing breastfeeding education is a significant determinant of type of counseling techniques used with clients. Further research is therefore needed to critically examine the content of the various training curricula of CBBC programs. This may show a need for a standardized training curriculum for all CBBC programs worldwide to make CBBCs more proficient and efficient, ensuring successful and optimum breastfeeding experiences for mothers and their newborns.
To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced serous ovarian cancers.
Immunohistochemical localization of CD8 T lymphocytes was performed on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was performed on microdissected tumor epithelium from 38 specimens to identify genes up- or down-regulated in specimens with differing numbers of tumor-infitrating CD8 T lymphocytes. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were performed combining CD8 T lymphocyte number and HLA-DMB expression with standard prognostic factors.
Marked CD8 T lymphocyte infiltration of the tumor epithelium is associated with a 20 month improvement in median overall survival. Additionally, when combined with cytoreduction status and age, CD8 T lymphocyte status is an independent prognostic factor for survival. Microarray analysis demonstrated HLA-DMB, a component of the major histocompatibility complex (MHC) II antigen-presentation machinery, to be differentially expressed in specimens with an abundance of tumor-infiltrating CD8 T lymphocytes. This relationship was validated at both the mRNA and protein levels. As well, high HLA-DMB expression in the tumor epithelium was associated with a significant improvement in median overall survival in both univariate and multivariate analyses.
Tumor cell expression of HLA-DMB is associated with increased numbers of tumor-infiltrating CD8 T lymphocytes and both are associated with improved survival in advanced serous ovarian cancer.
A procedure for isolating and identifying adenoviruses in microplates is described. Comparison tests with standard tube methods show an agreement of 92%. Virus isolations are greatly facilitated by the microplate method. This method is sensitive, economical, and especially applicable to large-scale epidemiological surveys.