Studying human fertility.
We very much welcome the National Children's Study The National Children’s Study (NCS) will examine the effects of environmental influences on the health and development of more than 100,000 children across the United States, following them from before birth until age 21. , which promises to raise the study of factors affecting reproduction and development to a new level. An impressive and exciting range of new methodologies is being developed (Chapin and Buck 2004; National Children's Study 2004).
However, we think it important to correct some of the inaccurate statements concerning the use of retrospective time to pregnancy (TTP TTP (thymidine triphosphate): see thymine. ) made by Tingen et al. (2004). We do not see prospective methods and the retrospective approach as alternatives; they are complementary, each having their strengths and weaknesses. Unfortunately, Tingen et al. presented a negative and distorted view of retrospective TTP studies, describing things that are "often" or "typically" done but that do not represent current best practice; then they used their description to denigrate den·i·grate
tr.v. den·i·grat·ed, den·i·grat·ing, den·i·grates
1. To attack the character or reputation of; speak ill of; defame.
2. all such studies. Although it is true that retrospective studies retrospective study,
a study in which a search is made for a relationship between one phenomenon or condition and another that occurred in the past (e.g. are subject to multiple potential "bias in recruitment, recall, and behavior or exposure trends" (Tingen et al. 2004), careful sampling and questionnaire design and use of appropriate methods of analysis can address most of these issues.
Retrospective studies are not necessarily pregnancy based. They can be conducted in random population-based samples and frequently are cross-sectional or birth cohort studies A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design.
In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute (Joffe 2000; Joffe and Li 1994; Karmaus et al. 1999; Sallmen et al. 1995; Schaumburg and Boldsen 1992; Schaumburg and Olsen 1989; Thonneau et al. 1999), thereby overcoming the problem that only women who eventually conceived are included. Even in pregnancy-based studies, if there are concerns about differential prenatal care prenatal care,
n the health care provided the mother and fetus before childbirth. (an issue in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. but not in western Europe Western Europe
The countries of western Europe, especially those that are allied with the United States and Canada in the North Atlantic Treaty Organization (established 1949 and usually known as NATO). , for example), recruitment could be based on births rather than pregnancies, obviously with loss of nonbirth outcomes. If sampling is population based, it is feasible to ascertain periods of unprotected intercourse not leading to conception (generally stipulating a minimum duration such as 6 months); these attempts can be added to the pregnancy-related TTP values to generate the "time of unprotected intercourse" (Karmaus et al. 1999).
Tingen et al. (2004) presented simple issues of questionnaire design negatively, but these problems can be easily solved. For example, if data are collected in relation to the starting time Noun 1. starting time - the time at which something is supposed to begin; "they got an early start"; "she knew from the get-go that he was the man for her"
commencement, get-go, offset, outset, showtime, start, kickoff, beginning, first instead of the conception time (Weinberg et al. 1994), behavior change Behavior change refers to any transformation or modification of human behavior. Such changes can occur intentionally, through behavior modification, without intention, or change rapidly in situations of mental illness. does not lead to bias but only to nondifferential loss of information.
A central issue is planning bias, the question being how to exclude accidental (unplanned) pregnancies without bias occurring if the exposure variable is associated with the degree of "plannedness." Retrospective studies can readily investigate this by following the standard guidance to collect full information for all pregnancies, including all covariates, and carry out parallel analyses with "unplanned pregnancy rate" as outcome variable (Weinberg et al. 1994). Prospective studies are unable to do this because only planners are recruited.
Tingen et al. (2004) stated that in TTP studies, "women are asked to recount their contraceptive contraceptive /con·tra·cep·tive/ (-sep´tiv)
1. diminishing the likelihood of or preventing conception.
2. an agent that so acts. and sexual history." This is incorrect; in TTP studies, women are not asked for this detailed information because it would be invasive and inaccurate. Instead, women are simply asked how long it took to conceive, a question that is acceptable and that most can answer. The replies give an accurate representation of the true TTP distribution (Baird et al. 1991; Joffe et al. 1993, 1995; Zielhuis et al. 1992), even with recall of up to 20 years Coffe et al. 1995). Although digit preference Digit preference is a cause that makes measuring e.g. blood pressure to give different results when different persons measure it. Different persons round off the value, either to a lower one or a higher one. (and other non-differential misclassification) can occur, the implication is that more respondents are required than would be the case with perfect information. Nevertheless, stable estimates of the TTP distribution can be obtained with approximately 200 values in each exposure group, or fewer in the case of ordered categories such as successive 5-year periods (Joffe 2000).
We agree that a major limitation of retrospective studies is that it is impossible to obtain detailed, timed information on exposures and key biologic events such as ovulation ovulation /ovu·la·tion/ (ov?u-la´shun) the discharge of a secondary oocyte from a graafian follicle.ov´ulatory
The discharge of an ovum from the ovary. , and difficult to ascertain certain covariates such as frequency or timing of intercourse. This is the key strength of the prospective design. On the other hand, retrospective studies are representative because, as already noted, sampling from the general population is available and planning bias can be handled. The questions are easily administered and answered, and the response rate is high. Even response bias can be avoided by nesting the TTP questions within a more general population survey, thus decoupling Decoupling
The occurrence of returns on asset classes diverging from their normal pattern of correlation.
Take for example stock and corporate bond returns, which normally rise and fall together. survey nonresponse from differential fertility or other motivation that would convert low response rates to response bias (Joffe 2000). Selection bias remains a potential problem for some retrospective designs but can be handled by appropriate statistical analysis allowing for truncation effects (Scheike and Jensen 1997).
Not only are prospective studies time-consuming and costly, and therefore likely to be rarely used, but they have important methodologic drawbacks. For example, it is impossible to distinguish the approximately 3% of couples who are sterile from those who merely take a long time to conceive (> 10% typically take > 12 months), unless follow-up is extremely long.
More seriously, prospective studies are dominated by the lack of a sampling frame (except in occupational studies) and by a potent combination of planning bias and response bias. They can include only couples who deliberately plan and are willing to volunteer for onerous monitoring. This is acceptable for internal comparisons (e.g., studying day-specific conception rates, each subject being her own control) but raises serious problems with external validity External validity is a form of experimental validity. An experiment is said to possess external validity if the experiment’s results hold across different experimental settings, procedures and participants. . Tingen et al. (2004) referred to this only in their Table 1--"Participants might be less representative of target population"--but not in the text; in contrast, Buck et al. (2004) admitted that women who plan their pregnancies may be systematically different from those who do not, that this may adversely affect external validity to a degree which cannot be empirically evaluated, and that the findings may not be generalizable gen·er·al·ize
v. gen·er·al·ized, gen·er·al·iz·ing, gen·er·al·iz·es
a. To reduce to a general form, class, or law.
b. To render indefinite or unspecific.
2. to all women.
The authors declare they have no competing financial interests.
Department of Epidemiology & Public Health
Imperial College Faculty of Medicine
London, United Kingdom
Tina Kold Jensen
Institute of Public Health
Department of Environmental Medicine
University of Southern Denmark As a national institution the University of Southern Denmark (SDU) comprises five faculties – Humanities, Science, Engineering, Social Sciences and Health Sciences totaling 32 departments, 11 research centers and a university library.
Baird DD, Weinberg CR, Rowland AS. 1991. Reporting errors in time-to-pregnancy data collected with a short questionnaire. Am J Epidemiol 133:1282-1290.
Buck GM, Lynch CD, Stanford JB, Sweeney AM, Schieve LA, Rockett JC, et al. 2004. Prospective pregnancy study designs for assessing reproductive and developmental toxicants. Environ Health Perspect 112:79-86.
Chapin RE, Buck GM. 2004. Our once-in-a-lifetime opportunity. Environ Health Perspect 112:67-68.
Joffe M. 2000. Time trends in biological fertility in Britain. Lancet 355:1961-1965.
Joffe M, Li Z. 1994. Male and female factors in fertility. Am J Epidemiol 140:921-929.
Joffe M, Villard L, Li Z, Plowman R, Vessey M. 1993. Long-term recall of time-to-pregnancy. Fertil Steril 60:99-104.
Joffe M, Villard L, Li Z, Plowman R, Vessey M. 1995. A time to pregnancy questionnaire designed for long term recall: validity in Oxford, England. J Epidemiol Community Health 49:314-319.
Karmaus W, Juul S, European Infertility infertility, inability to conceive or carry a child to delivery. The term is usually limited to situations where the couple has had intercourse regularly for one year without using birth control. and Subfecundity Group. 1999. Infertility and subfecundity in population-based samples from Denmark, Germany, Italy, Poland and Spain. Eur J Public Health 9:229-235.
National Children's Study. 2004. National Children's Study Homepage. Available: http://nationalchildrensstudy.gov/ [accessed 20 March 2004].
Sallmen M, Lindbohm M-L M-L Main Lobe , Kyyronen P, Nykyri E, Anttila A, Taskinen H, et al. 1995. Reduced fertility among women exposed to organic solvents. Am J Ind Med 27:699-713.
Schaumburg I, Boldsen JL. 1992. Waiting time to pregnancy and pregnancy outcome among Danish workers in the textile, clothing, and footwear industries. Scand J Soc Med 20:110-114.
Schaumburg I, Olsen J. 1989. Time to pregnancy among Danish pharmacy assistants. Scand J Work Environ Health 15:222-226.
Scheike T, Jensen T. 1997. A discrete survival model with random effects Random effects can refer to:
Thonneau P, Abell A, Larsen SB, Bonde JP, Joffe M, Clavert A, et al. 1999. Effects of pesticide exposure on time to pregnancy: results of a multicenter study in France and Denmark. ASCLEPIOS Study Group. Am J Epidemiol 150:157-183.
Tingen C, Stanford JB, Dunson BB. 2004. Methodologic and statistical approaches to studying human fertility and environmental exposure. Environ Health Perspect 112:87-93.
Weinberg CR, Baird DD, Wilcox AJ. 1994. Sources of bias in studies of time to pregnancy. Stat Med 13:671-681.
Zielhuis GA, Hulseher MEJL, Florack EIM EIM Enterprise Incentive Management
EIM Enterprise Information Management
EIM Enterprise Identity Mapping (IBM)
EIM Enterprise Instant Messaging
EIM Employee Internet Management
EIM European Institute for the Media . 1992. Validity and reliability of a questionnaire on fecundability fecundability /fe·cun·da·bil·i·ty/ (fe-kun?dah-bil´i-te) the probability that conception will occur in a given population of couples during a specific time period. . Int J Epidemiol 21:1151-1156.