scispace - formally typeset
Search or ask a question
Posted ContentDOI

A compelling symmetry: The extended fetuses-at-risk perspective on modal, optimal and relative birthweight and gestational age

24 Aug 2020-bioRxiv (Cold Spring Harbor Laboratory)-
TL;DR: Changes in the first derivative of the fetuses-at-risk birth and perinatal death rates underlie several births-based per inatal phenomena and this explanation further unifies the Fetuses- at-risk and births- based models of perinnatal death.
Abstract: Background The relationship between several intriguing perinatal phenomena, namely, modal, optimal, and relative birthweight and gestational age, remains poorly understood, especially the mechanism by which relative birthweight and gestational age resolve the paradox of intersecting perinatal mortality curves. Methods Birthweight and gestational age distributions and birthweight- and gestational age-specific perinatal death rates of low- and high-risk cohorts in the United States, 2004-2015, were estimated using births-based and extended fetuses-at-risk formulations. The relationships between these births-based distributions and rates, and the first derivatives of fetuses-at-risk birth and perinatal death rates were examined in order to assess how the rate of change in fetuses-at-risk rates affects gestational age distributions and births-based perinatal death rate patterns. Results Modal gestational age typically exceeded optimal gestational age because both were influenced by the peak in the first derivative of the birth rate, while optimal gestational age was additionally influenced by the point at which the first derivative of the fetuses-at-risk perinatal death rate showed a sharp increase in late gestation. The clustering and correlation between modal and optimal gestational age within cohorts, the higher perinatal death rate at optimal gestational age among higher-risk cohorts, and the symmetric left-shift in births-based gestational age-specific perinatal death rates in higher-risk cohorts explained how relative gestational age resolved the paradox of intersecting perinatal mortality curves. Conclusions Changes in the first derivative the fetuses-at-risk birth and perinatal death rates underlie several births-based perinatal phenomena and this explanation further unifies the fetuses-at-risk and births-based models of perinatal death.

Summary (3 min read)

Introduction

  • Several studies have shown that population cohorts based on nationality, racial origin and other characteristics vary substantially in terms of birthweight distribution and optimal birthweight (i.e., the birthweight at which perinatal mortality rates are lowest) [1–9].
  • A related enigmatic finding is that optimal birthweight typically exceeds modal birthweight (i.e., the maximum of the birthweight distribution) [7–9].
  • One of the first attempts at resolving the paradox involved an intriguing reformulation involving relative birthweight and relative gestational age (i.e., with absolute birthweight or gestational age in each population recast in terms of its mean and standard deviation) [7,17].
  • This unifies the fetuses-at-risk and births-based models of perinatal death and also explains various perinatal phenomena including the early gestation exponential decline and the late gestation exponential increase in births-based perinatal mortality rates, and also the paradox of intersecting perinatal morality curves [29,30].

Background and rationale for the study

  • November 30, 2020 2 / 15 Funding: KSJ’s work is supported by an Investigator award from the BC Children’s Hospital Research Institute.
  • The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  • The author has declared that no competing interests exist.
  • On the other hand, the late gestation rise in births-based perinatal death rates occurs because reductions in acceleration (or a deceleration) in the birth rate at later gestation leads to a relatively smaller increase (or a fall) in the number of births, whereas the number of perinatal deaths rises sharply because of the rapidly accelerating fetuses-at-risk perinatal death rate [29,30].

Data source and analysis

  • All live births and stillbirths in the United States from 2004 to 2015 were included in the study with data obtained from the fetal death and period linked birth-infant death files of the National Center for Health Statistics.
  • The study population was restricted to births with a clinical estimate of gestation between 20 and 43 weeks.
  • Thus, a positive first derivative of the birth rate represents an accelerating birth rate while a negative first derivative represents a decelerating birth rate.
  • All analyses were based on anonymized, publicly available data and ethics approval for the study was not sought.

Results

  • There were 47,626,172 live births and stillbirths between 20 and 43 weeks’ gestation in the study population.
  • The births-based perinatal death rate curves of the two cohorts intersected; perinatal death rates were lower among twins<38 weeks’ and higher at 38 weeks’ gestation and over compared with perinatal death rates among low-risk singletons (Fig 1E).
  • The peak in the first derivative of the birth rate was also positively correlated with optimal gestational age and the gestational age at which the first derivative of the fetuses-at-risk perinatal death rate showed a sharp increase in late gestation (Table 1).

Discussion

  • This study confirms that the gestational age distribution and modal gestational age are determined by the rate of change in the birth rate, while the births-based gestational age-specific perinatal death rate pattern and optimal gestational age are influenced by both the rate of change in the birth rate and the rate of change in the fetuses-at-risk perinatal death rate [29,30].
  • The latter increases abruptly in late gestation (e.g., at 37, 38, 41 and 40 weeks among triplets, twins, singletons of women with hypertension, and low-risk singletons, respectively; Fig 4C) and this ensures that optimal gestational age (35, 38, 39 weeks and 40 weeks, respectively among the four cohorts; Fig 4D) typically exceeds modal gestational age.
  • The perinatal death rate achieved at optimal gestational age is higher in higher-risk cohorts compared with lower-risk cohorts.
  • These positive correlations mean that a left-shift in the peak of the first derivative of the birth rate will result in a lower modal gestational age, and that leftshifts in the first derivatives of the birth rate and the fetuses-at-risk perinatal death rate will result in a lower optimal gestational age.

Strengths

  • The empirical patterns in this study were based on a large perinatal dataset that permitted examination of several low- and high-risk cohorts.
  • First derivatives of fetuses-at-risk birth and perinatal death rates were calculated to provide insight into mechanisms by which changes in these rates influenced gestational age distributions and births-based perinatal mortality patterns of diverse populations.
  • The use of first derivatives in this context is appropriate because the exponentially rising birth rate conceals large differences in the rate of change in the birth rate between early and later gestation.

Limitations

  • The study population was restricted to births 20–43 week’s gestation and pregnancy losses that occurred prior to 20 weeks were not included in the study’s fetuses-at-risk denominators.
  • Also, the data source provided gestational age by week and not days, and this imprecision likely resulted in small inaccuracies in the indices estimated.
  • Gestational age-specific fetal growth-restriction rates could not be incorporated into the models because such information was not available.
  • Thus, changes in obstetric and neonatal care, which have impacted birth and perinatal mortality rates over recent decades, likely did not compromise the relative gestational age-specific analyses in this study as contrasted cohorts (e.g., singletons of low-risk women vs twins) would have been affected almost uniformly by period and cohort effects.
  • Inferences based on this large dataset are unlikely to have been seriously compromised.

Interpretation and conclusions

  • The left-shift in the distribution of the first derivative of the birth rate in higher-risk cohorts results in a symmetrical left-shift in the gestational age distribution and an inversely symmetrical left-shift in the births-based gestational age-specific perinatal death rate curve.
  • The symmetric left-shift in the gestational age distribution and the symmetric and inverse left-shift in the births-based perinatal death rate in higher-risk cohorts ensures that relative gestational age-and relative birthweight-specific perinatal death rates are higher among higher-risk cohorts at all gestational ages and birthweights.
  • Such symmetry may invoke the concept of epidemiologic beauty, though it should be noted that in modern physics, beauty is regarded by some as a characteristic of nature and by others as an ill-conceived aesthetic bias that has led physics astray.
  • Irrespective of whether or not one finds the symmetry appealing, these explanations provide insight into several birth-based phenomena that have previously defied resolution.

Did you find this useful? Give us your feedback

Figures (6)

Content maybe subject to copyright    Report

RESEARCH ARTICLE
A compelling symmetry: The extended
fetuses-at-risk perspective on modal, optimal
and relative birthweight and gestational age
K. S. Joseph
ID
*
Department of Obstetrics and Gynaecology, School of Population and Public Health, University of British
Columbia and the Children’s and Women’s Hospital and Health Centre of British Columbia, Kelowna, Canada
* kjoseph@cw.bc.ca
Abstract
Background
The relationship between several intriguing perinatal phenomena, namely, modal, optimal,
and relative birthweight and gestational age, remains poorly understood, especially the
mechanism by which relative birthweight and gestational age resolve the paradox of inter-
secting perinatal mortality curves.
Methods
Birthweight and gestational age distributions and birthweight- and gestational age-specific peri-
natal death rates of low- and high-risk cohorts in the United States, 2004–2015, were estimated
using births-based and extended fetuses-at-risk formulations. The relationships between these
births-based distributions and rates, and the first derivatives of fetuses-at-risk birth and perina-
tal death rates were examined in order to assess how the rate of change in fetuses-at-risk
rates affects gestational age distributions and births-based perinatal death rate patterns.
Results
Modal gestational age typically exceeded optimal gestational age because both were influ-
enced by the peak in the first derivative of the birth rate, while optimal gestational age was
additionally influenced by the point at which the first derivative of the fetuses-at-risk perinatal
death rate showed a sharp increase in late gestation. The clustering and correlation
between modal and optimal gestational age within cohorts, the higher perinatal death rate at
optimal gestational age among higher-risk cohorts, and the symmetric left-shift in births-
based gestational age-specific perinatal death rates in higher-risk cohorts explained how rel-
ative gestational age resolved the paradox of intersecting perinatal mortality curves.
Conclusions
Changes in the first derivative of the fetuses-at-risk birth and perinatal death rates underlie
several births-based perinatal phenomena and this explanation further unifies the fetuses-
at-risk and births-based models of perinatal death.
PLOS ONE
PLOS ONE | https://doi.org/10.1371/journal.pone.0238673 November 30, 2020 1 / 15
a1111111111
a1111111111
a1111111111
a1111111111
a1111111111
OPEN ACCESS
Citation: Joseph KS (2020) A compelling
symmetry: The extended fetuses-at-risk
perspective on modal, optimal and relative
birthweight and gestational age. PLoS ONE 15(11):
e0238673. https://doi.org/10.1371/journal.
pone.0238673
Editor: Frank T. Spradley, University of Mississippi
Medical Center, UNITED STATES
Received: August 19, 2020
Accepted: November 12, 2020
Published: November 30, 2020
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
process; therefore, we enable the publication of
all of the content of peer review and author
responses alongside final, published articles. The
editorial history of this article is available here:
https://doi.org/10.1371/journal.pone.0238673
Copyright: © 2020 K. S. Joseph. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: The data are publicly
available at https://www.cdc.gov/nchs/data_
access/vitalstatsonline.htm.

Introduction
Several studies have shown that population cohorts based on nationality, racial origin and
other characteristics vary substantially in terms of birthweight distribution and optimal birth-
weight (i.e., the birthweight at which perinatal mortality rates are lowest) [19]. A related enig-
matic finding is that optimal birthweight typically exceeds modal birthweight (i.e., the
maximum of the birthweight distribution) [79]. Although it is unclear why many fetuses in
diverse populations are born before reaching optimal size, these findings have led to recom-
mendations regarding the need for population-specific standards of birthweight for identifying
small infants at risk of perinatal death [8].
Some support for the proposition that perinatal mortality risk is best assessed through pop-
ulation-specific standards of birthweight is also forthcoming from the literature on the para-
dox of intersecting perinatal mortality curves. This phenomenon was first described over 50
years ago by Yerushalmy who showed that neonatal death rates favoured the low birthweight
infants of mothers who smoked (compared with the low birthweight infants of mothers who
did not smoke), while the opposite was true at higher birthweights [10]. The paradox is now
recognized to be a general phenomenon [1125] that is observed across numerous contrasts
(e.g., infants of hypertensive vs normotensive mothers [14], and singletons vs twins
[13,15,16]), outcomes (e.g., stillbirths and cerebral palsy [1119]) and indices of prematurity
(gestational age and birthweight [1125]). One of the first attempts at resolving the paradox
involved an intriguing reformulation involving relative birthweight and relative gestational
age (i.e., with absolute birthweight or gestational age in each population recast in terms of its
mean and standard deviation) [7,17]. When birthweight- and gestational age-specific perinatal
death rates are quantified in terms of relative birthweight or relative gestational age, infants of
mothers who smoke (have hypertension, etc) have higher rates of perinatal death at all birth-
weights and gestational ages [57,9,12,14,15,17,2528].
A recent paper [29] offered evidence in favour of the proposition that the rate of change in
the birth rate of a population (i.e., the first derivative of the population’s fetuses-at-risk birth
rate) determines the population’s gestation age distribution, and that the first derivatives of the
birth rate and the fetuses-at-risk perinatal mortality rate together determine the population’s
births-based gestational age-specific perinatal mortality pattern. This unifies the fetuses-at-risk
and births-based models of perinatal death and also explains various perinatal phenomena
including the early gestation exponential decline and the late gestation exponential increase in
births-based perinatal mortality rates, and also the paradox of intersecting perinatal morality
curves [29,30]. In this paper, the first derivatives of the birth rate and the fetuses-at-risk perina-
tal mortality rate are used to explain other previously unexplained phenomena, namely,
modal, optimal and relative birthweight and gestational age. Understanding these phenomena,
especially the mechanism by which relative gestational age uncrosses intersecting perinatal
mortality curves, will provide further support for unifying the two models of perinatal death.
Methods
Background and rationale for the study
The seemingly opposed perspectives of the births-based and fetuses-at-risk models [29] can be
reconciled by viewing the early gestation exponential decline in births-based perinatal death
rates as being the product of an initially accelerating birth rate (i.e., steep increase in the first
derivative of the fetuses-at-risk birth rate) and a fetuses-at-risk perinatal death rate that is sta-
ble or slowly accelerating in early gestation (no change or a small increase in the first derivative
of the fetuses-at-risk perinatal death rate). Similarly, the late gestation increase in births-based
PLOS ONE
Modal, optimal and relative gestational age
PLOS ONE | https://doi.org/10.1371/journal.pone.0238673 November 30, 2020 2 / 15
Funding: KSJ’s work is supported by an
Investigator award from the BC Children’s Hospital
Research Institute. The funder had no role in study
design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing interests: The author has declared that
no competing interests exist.

perinatal death rates can be explained as a product of a decelerating birth rate (i.e., sharp
declines in the first derivative) and an abrupt acceleration in the fetuses-at-risk perinatal death
rate (i.e., sharp increase in the first derivative). Births-based perinatal death rates fall exponen-
tially in early gestation because the accelerating birth rate results in an increasing number of
births, whereas the number of perinatal deaths is essentially unchanged as a consequence of
the stable or slowly accelerating fetuses-at-risk perinatal death rate. On the other hand, the late
gestation rise in births-based perinatal death rates occurs because reductions in acceleration
(or a deceleration) in the birth rate at later gestation leads to a relatively smaller increase (or a
fall) in the number of births, whereas the number of perinatal deaths rises sharply because of
the rapidly accelerating fetuses-at-risk perinatal death rate [29,30]. Compared with low-risk
cohorts, higher-risk cohorts show a steeper increase in the first derivative of the birth rate at
early gestation (i.e., greater acceleration in the birth rate), and an earlier peak and an earlier
decline in this first derivative at late gestation (i.e., earlier reductions in acceleration in the
birth rate). The left-shift in the distribution of the first derivative of the birth rate in higher-
risk cohorts is responsible for a left-shift in gestational age distributions and in births-based
perinatal death rate curves. The latter left-shift in births-based perinatal death rates of higher-
risk cohorts results in the paradox of intersecting perinatal mortality curves [29,30].
The rationale for the present study was premised on the above-mentioned propositions: if
the rate of change in the birth rate determines the birth rate pattern and influences the gesta-
tional age distribution, and if the rate of change in the birth rate and the rate of change in the
fetuses-at-risk perinatal death rate together influence the pattern of births-based gestational
age- and birthweight-specific perinatal death rates, it is likely that the rate of change in fetuses-
at-risk birth and perinatal death rates also underlie the phenomena of modal, optimal, and rel-
ative birthweight and relative gestational age. The rate of change in the birth rate is of particu-
lar interest as it’s magnitude at specific points in gestation is not immediately evident from the
exponentially increasing birth rate.
Data source and analysis
All live births and stillbirths in the United States from 2004 to 2015 were included in the study
with data obtained from the fetal death and period linked birth-infant death files of the
National Center for Health Statistics. The study population was restricted to births with a clini-
cal estimate of gestation between 20 and 43 weeks. Twelve low- and high-risk cohorts were
identified, namely, singletons of women who did not have hypertension or diabetes (referred
to as low-risk singletons), singletons of women with hypertension, singletons of women with
diabetes, singletons of women with hypertension and diabetes, White singletons, Black single-
tons, singletons of women aged 25–29 years, singletons of women aged 35 years, singletons
of women with a previous preterm birth, singletons of women without a previous preterm
birth, twins, and triplets.
Preliminary examination of the birthweight distribution showed substantial ounce and
digit preference in birthweight values (S1 Fig in S1 Appendix) and birthweight was therefore
categorized into 28 g birthweight groups centred on the gram equivalent of each complete
ounce. The birthweight distribution and its modal value, and the birthweight-specific perinatal
death rate (including stillbirths and neonatal deaths) and its lowest point (i.e., optimal birth-
weight) were then estimated by fitting splines to the log transformed birthweight groups and
birthweight-specific perinatal death rates using the Transreg procedure in the SAS statistical
software package (SAS Institute, Cary, NC).
The frequency distribution of gestational age and gestational age-specific perinatal death
rates were calculated under the births-based formulation (expressed per 1,000 total births) and
PLOS ONE
Modal, optimal and relative gestational age
PLOS ONE | https://doi.org/10.1371/journal.pone.0238673 November 30, 2020 3 / 15

modal and optimal gestational age were estimated. Gestational age-specific birth rates and ges-
tational age-specific fetuses-at-risk perinatal death rates (both expressed per 1,000 fetus-
weeks) were also calculated using the extended fetuses-at-risk formulation [28,3136]. The
number of births (or perinatal deaths) at any gestational week constituted the numerator for
these fetuses-at-risk rates, while the fetal-time accrued by the fetuses at risk over the gestational
week in question constituted the denominator. Fetal-time was estimated by averaging the
number of fetuses at the beginning and the end of the gestational week of interest (which
included fetuses delivered at that gestational week and those delivered subsequently; S1 and S2
Tables in S1 Appendix).
The Expand procedure in the SAS statistical package was used to estimate the first deriva-
tives of the fetuses-at-risk gestational age-specific birth rates and the fetuses-at-risk gestational
age-specific perinatal death rates (S3 Table in S1 Appendix). The first derivatives were com-
puted from cubic splines fitted to the fetuses-at-risk birth and perinatal death rates and quanti-
fied the rate of change (increase or decrease) in these rates at each gestational week. It may be
helpful to view the birth rate (births per 1,000 fetus-weeks) and its first derivative (births per
1,000 fetus-weeks per week, or births per 1,000 fetus-weeks
2
) as being analogous to velocity
(metres/sec) and acceleration/deceleration (metres per second per second, or metres per sec-
ond
2
), respectively. Thus, a positive first derivative of the birth rate represents an accelerating
birth rate while a negative first derivative represents a decelerating birth rate. A positive and
continually increasing first derivative of the birth rate signifies a progressively increasing accel-
eration in the birth rate, while a positive and progressively decreasing first derivative signifies a
birth rate that is increasing but at a slower rate (i.e., with reduced acceleration) than in previ-
ous gestational weeks.
Birthweight and gestational age distributions, gestational age-specific birth rates, the deriva-
tives of the birth rates, births-based and fetuses-at-risk perinatal death rates, and the deriva-
tives of the fetuses-at-risk perinatal death rates were estimated for each low- and high-risk
cohort and graphed in order to examine potential relationships with modal, optimal and rela-
tive birthweight and gestational age (i.e., with the latter calculated using z-scores based on the
mean and standard deviation of the birthweight and gestational age distributions of each
cohort). Correlations between the gestational age at which the first derivative of the birth rate
peaked and the mean, mode, median and optimal birthweight and gestational age were esti-
mated in the 12 cohorts using Pearson correlation coefficients (r). Correlations between the
gestational age at which the first derivative of the fetuses-at-risk perinatal death rate showed an
abrupt upward increase at late gestation and optimal birthweight and optimal gestational age
were similarly assessed.
All analyses were based on anonymized, publicly available data and ethics approval for the
study was not sought.
Results
There were 47,626,172 live births and stillbirths between 20 and 43 weeks’ gestation in the
study population. The rate of perinatal death varied substantially between the different cohorts;
it was 8.2 per 1,000 total births among low-risk singletons, and 72.4 per 1,000 total births
among triplets (S4 Table in S1 Appendix).
Fig 1A and 1B shows birthweight distributions, birthweight-specific perinatal death rates
and modal and optimal birthweight among low-risk singletons and twins. Modal birthweight
was substantially lower than optimal birthweight in both cohorts, and modal birthweight and
optimal birthweight were substantially lower among twins; similarly, modal and optimal gesta-
tional age were lower among twins (37 and 38 weeks, respectively) compared with low-risk
PLOS ONE
Modal, optimal and relative gestational age
PLOS ONE | https://doi.org/10.1371/journal.pone.0238673 November 30, 2020 4 / 15

singletons (39 weeks and 40 weeks, respectively; Fig 1C and 1D). The lowest gestational age-
specific perinatal death rate among twins was higher than the lowest perinatal death rate
among low-risk singletons. The births-based perinatal death rate curves of the two cohorts
intersected; perinatal death rates were lower among twins <38 weeks’ and higher at 38 weeks’
gestation and over compared with perinatal death rates among low-risk singletons (Fig 1E).
When gestational age-specific perinatal death rates were based on relative gestational age (z-
scores), twins had higher rates of perinatal death at all gestational ages (Fig 1F).
Fig 2 shows the birth rate, the rate of change in the birth rate and the gestational age distri-
bution among the singletons of low-risk women and twins. The first derivative of the birth rate
was left-shifted (Fig 2B), the birth rate was considerably higher at each gestational week (Fig
2A), and the gestational age distribution was substantially left-shifted among twins (Fig 2C).
Fig 3 shows the birth rates and their first derivatives, the fetuses-at-risk perinatal death rates
and their derivatives and births-based perinatal death rates in the two cohorts. The first
Fig 1. Birthweight distributions and birthweight-specific perinatal death rates among singletons of low-risk women (i.e., without
hypertension or diabetes; Panel A) and twins (Panel B); gestational age distributions and gestational age-specific perinatal death rates among
singletons of low-risk women (Panel C) and twins (Panel D); and births-based gestational age-specific perinatal death rates (Panel E) and
births-based relative gestational age-specific perinatal death rates (Panel F) among singletons of low-risk women and twins, United States,
2004–2015.
https://doi.org/10.1371/journal.pone.0238673.g001
PLOS ONE
Modal, optimal and relative gestational age
PLOS ONE | https://doi.org/10.1371/journal.pone.0238673 November 30, 2020 5 / 15

References
More filters
Journal ArticleDOI
TL;DR: Evidence presented here suggests the link between birthweight and health outcomes may not be causal, and methods of analysis that assume causality are unreliable at best, and biased at worst.
Abstract: Birthweight is one of the most accessible and most misunderstood variables in epidemiology. A baby's weight at birth is strongly associated with mortality risk during the first year and, to a lesser degree, with developmental problems in childhood and the risk of various diseases in adulthood. Epidemiological analyses often regard birthweight as on the causal pathway to these health outcomes. Under this assumption of causality, birthweight is used to explain variations in infant mortality and later morbidity, and is also used as an intermediate health endpoint in itself. Evidence presented here suggests the link between birthweight and health outcomes may not be causal. Methods of analysis that assume causality are unreliable at best, and biased at worst. The category of 'low birthweight' in particular is uninformative and seldom justified. The main utility of the birthweight distribution is to provide an estimate of the proportion of small preterm births in a population (although even this requires special analytical methods). While the ordinary approaches to birthweight are not well grounded, the links between birthweight and a range of health outcomes may nonetheless reflect the workings of biological mechanisms with implications for human health.

836 citations

Journal ArticleDOI
TL;DR: Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity.
Abstract: Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, pre-eclampsia and chronic hypertension with superimposed pre-eclampsia. Pre-eclampsia complicates about 3% of pregnancies, and all hypertensive disorders affect about five to 10% of pregnancies. Secular increases in chronic hypertension, gestational hypertension and pre-eclampsia have occurred as a result of changes in maternal characteristics (such as maternal age and pre-pregnancy weight), whereas declines in eclampsia have followed widespread antenatal care and use of prophylactic treatments (such as magnesium sulphate). Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity. Hypertensive disorders are associated with higher rates of maternal, fetal and infant mortality, and severe morbidity, especially in cases of severe pre-eclampsia, eclampsia and haemolysis, elevated liver enzymes and low platelets syndrome.

807 citations

Journal ArticleDOI
TL;DR: The objective was to evaluate gestation‐specific risks of stillbirth, neonatal and post‐neonatal mortality in pregnant women and to establish a baseline level of confidence in the results.

335 citations

Journal ArticleDOI
TL;DR: The risk of unexplained stillbirth was least in preterm pregnancies, rising fourfold after 39 weeks to a maximum at 41 weeks, in contrast to the rate, which was nineteen times lower.

298 citations

Journal ArticleDOI
TL;DR: The present analysis suggests that the prevention of early delivery would benefit babies of all birth weights, and indicates that gestational age is a powerful predictor of birth weight and perinatal survival.
Abstract: BACKGROUND. The strong association between birth weight and perinatal mortality is due both to gestational age and to factors unrelated to gestational age. Conventional analysis obscures these separate contributions to perinatal mortality, and overemphasizes the role of birth weight. An alternative approach is used here to separate gestational age from other factors. METHODS. Data are from 400,000 singleton births in the Norwegian Medical Birth Registry. The method of Wilcox and Russell is used to distinguish the contributions to perinatal mortality made by gestational age and by relative birth weight at each gestational age. RESULTS. Gestational age is a powerful predictor of birth weight and perinatal survival. After these effects of gestational age are controlled for, relative birth weight retains a strong association with survival. CONCLUSIONS. Current public health policies in the United States emphasize the prevention of low birth weight. The present analysis suggests that the prevention of early de...

260 citations

Frequently Asked Questions (1)
Q1. What are the contributions mentioned in the paper "A compelling symmetry: the extended fetuses-at-risk perspective on modal, optimal and relative birthweight and gestational age" ?

The relationships between these births-based distributions and rates, and the first derivatives of fetuses-at-risk birth and perinatal death rates were examined in order to assess how the rate of change in fetuses-at-risk rates affects gestational age distributions and births-based perinatal death rate patterns.