Implications of Using a Fetuses‐at‐Risk Approach When Fetuses Are Not at Risk

Basso, Olga

doi:10.1111/ppe.12254

Cited by 38 publications

(67 citation statements)

References 28 publications

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“…Our study was also conditioned on having a live-birth and potentially prone to competing-risks bias, although this would likely result in the exposure appearing protective given the association of phthalates with reduced fecundability and pregnancy loss (Braun et al 2017; Messerlian et al 2016). However, consideration of including at-risk fetuses remains controversial (Basso 2016) and further empirical testing of potential biases may be warranted (Schisterman and Sjaarda 2016). Also, co-exposure to other chemicals of concern was not accounted for and exposure to phthalates may be reflective of other unknown lifestyle or fertility factors that might be associated with birth weight.…”

Section: Discussionmentioning

confidence: 99%

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Messerlian

Braun

Mínguez-Alarcón

et al. 2017

Environment International

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Background Ortho-phthalates are known endocrine disruptors. Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight; however, the effect of paternal and maternal preconception exposure remains understudied. Objectives To investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight. Methods The study comprised 364 singletons born to 364 mothers and 195 fathers (195 couples) from the EARTH Study, a prospective cohort of couples from Boston, MA. Births were categorized by mode of conception: in-vitro fertilization based (IVF) (n=208) or non-IVF based (n=156, intrauterine insemination or non-medically assisted/natural conception). We measured urinary concentrations of eleven phthalate metabolites in maternal (n=1,425) and paternal (n=489) preconception and maternal prenatal (n=781) samples. Birth weight was abstracted from delivery records. Covariate-adjusted associations between loge-phthalate metabolite concentrations and birth weight were evaluated separately by mode of conception using multivariable linear regression. Results Each loge-unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (ΣDEHP) metabolites was associated with a 90 gram (95% CI: −165, −15) decrease in birth weight among IVF singletons, but not among non-IVF singletons (18 grams; 95% CI: −76, 113). Additional adjustment for maternal prenatal ΣDEHP concentrations modestly strengthened findings among IVF singletons. While few associations were found with maternal preconception phthalate metabolites, we observed an inverse relationship between several maternal prenatal urinary phthalate metabolite concentrations and birth weight among IVF singletons in covariate-adjusted models. However, with further adjustment for specific paternal phthalate metabolite concentrations, these associations were attenuated and no longer significant. Conclusions Paternal preconception urinary concentration of ΣDEHP metabolites was associated with a decrease in birth weight among IVF-conceived singletons. These results, if replicated, highlight the importance of preconception health, especially among subfertile couples.

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Section: Discussionmentioning

confidence: 99%

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Messerlian

Braun

Mínguez-Alarcón

et al. 2017

Environment International

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“…Rates calculated under the fetuses‐at‐risk model were incidence density rates expressed per 1000 fetus‐weeks . Although the analyses presented focus on perinatal death rates, rates were also estimated for stillbirths and neonatal deaths separately …”

Section: Methodsmentioning

confidence: 99%

Towards a unified perinatal theory: Reconciling the births‐based and fetus‐at‐risk models of perinatal mortality

Joseph

2019

Paediatric Perinatal Epid

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Background There is a need to reconcile the opposing perspectives of the births‐based and fetuses‐at‐risk models of perinatal mortality and to formulate a coherent and unified perinatal theory. Methods Information on births in the United States from 2004 to 2015 was used to calculate gestational age‐specific perinatal death rates for low‐ and high‐risk cohorts. Cubic splines were fitted to the fetuses‐at‐risk birth and perinatal death rates, and first and second derivatives were estimated. Births‐based perinatal death rates, and fetuses‐at‐risk birth and perinatal death rates and their derivatives, were examined to identify potential inter‐relationships. Results The rate of change in the birth rate dictated the pattern of births‐based perinatal death rates in a triphasic manner: increases in the first derivative of the birth rate at early gestation corresponded with exponential declines in perinatal death rates, the peak in the first derivative presaged the nadir in perinatal death rates, and late gestation declines in the first derivative coincided with an upturn in perinatal death rates. Late gestation increases in the first derivative of the fetuses‐at‐risk perinatal death rate matched the upturn in births‐based perinatal death rates. Differences in birth rate acceleration/deceleration among low‐ and high‐risk cohorts resulted in intersecting perinatal mortality curves. Conclusion The first derivative of the birth rate links a cohort's fetuses‐at‐risk perinatal death rate to its births‐based perinatal death rate, and cohort‐specific differences in birth rate acceleration/deceleration are responsible for the intersecting perinatal mortality curves paradox. This mechanistic explanation unifies extant models of perinatal mortality and provides diverse insights.

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“…72 However, the relevance of such considerations is questionable since the population at risk is live-born children and the fetuses-at-risk approach can produce biased estimates for postnatal outcomes. 73,74 …”

Section: Epidemiological Studies Of Paternal Preconception Exposuresmentioning

confidence: 99%

Fathers Matter: Why It’s Time to Consider the Impact of Paternal Environmental Exposures on Children’s Health

Messerlian²,

2017

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Purpose Despite accumulating evidence from experimental animal studies showing that paternal environmental exposures induce genetic and epigenetic alterations in sperm which in turn increase the risk of adverse health outcomes in offspring, there is limited epidemiological data on the effects of human paternal preconception exposures on children’s health. We summarize animal and human studies showing that paternal preconception environmental exposures influence offspring health. We discuss specific approaches and designs for human studies to investigate the health effects of paternal preconception exposures, the specific challenges these studies may face, and how we might address them. Recent Findings In animal studies, paternal preconception diet, stress, and chemical exposures have been associated with offspring health and these effects are mediated by epigenetic modifications transmitted through sperm DNA, histones, and RNA. Most epidemiological studies have examined paternal preconception occupational exposures and their effect on the risk of birth defects and childhood cancer; few have examined the effects of low-level general population exposure to environmental toxicants. While the design and execution of epidemiological studies of paternal preconception exposures face challenges, particularly with regard to selection bias and recruitment, we believe these are tractable and that preconception studies are feasible. Summary New or augmented prospective cohort studies would be the optimal method to address the critical knowledge gaps on the effect of paternal preconception exposures on prevalent childhood health outcomes. Determining if this period of life represents a window of heightened vulnerability would improve our understanding of modifiable risk factors for children’s health and wellbeing.

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Implications of Using a Fetuses‐at‐Risk Approach When Fetuses Are Not at Risk

Cited by 38 publications

References 28 publications

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

Towards a unified perinatal theory: Reconciling the births‐based and fetus‐at‐risk models of perinatal mortality

Fathers Matter: Why It’s Time to Consider the Impact of Paternal Environmental Exposures on Children’s Health

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