Early neonatal mortality, asphyxia related deaths, and timing of low risk births in Hesse, Germany, 1990-8: observational study
BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7256.274 (Published 29 July 2000) Cite this as: BMJ 2000;321:274All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The report by Heller et al suggesting a higher rate of asphyxia
related deaths in low-risk pregnancies at night is of great interest (1).
A key question is what percentage of these deaths were potentially
preventable. We have reviewed the timing of delivery in a recent
consecutive case series of 22 infants with early onset moderate to severe
neonatal encephalopathy plus cord blood acidosis (2). We have previously
reported that half of the cases were associated with unpreventable
catastrophic events or antenatal hypoxia. These cases were equally
distributed between delivery during the day or night. In the remaining 50%
of cases, markedly non-reassuring fetal heart rate traces were either not
recognised or not acted on in a timely manner by the primary care giver.
Twice as many of these cases were delivered during the night compared with
during the day.
These data suggest that the inherent difficulties of fetal monitoring
in clinical practice are magnified at night by fatigue and a relative
reluctance to consult more experienced staff. Thus although previous
correspondents are quite right to point out the selective nature of the
population studied by Heller and colleagues, their results provide an
important indication of where practical efforts to improve fetal
monitoring should be focussed.
1. Heller G, Misselwitz B, Schmidt S. Early neonatal mortality,
asphyxia related deaths, and timing of low risk births in Hesse, Germany,
1990-8: observational study. BMJ 2000;321:274-5.
2. Westgate JA, Gunn AJ, Gunn TR. Antecedents of neonatal
encephalopathy with fetal acidaemia at term. Br J Obstet Gynaecol
1999;106:774-82.
Competing interests: No competing interests
Does birth during the night predispose for increased early neonatal mortality among the low risk ter
Editor: Article by Gunther Heller, Bjorn Misselwitz and Stephan
Schmidt is an interesting observation.1 The results were similar to the
studies published in this journal earlier.2,3 We have analyzed our unit's
neonatal database from January 1995 to December 1999. We have also found
the similar results.
Our neonatal unit is a level III neonatal unit of a tertiary care
high-risk referral perinatal center in a teaching institution. We included
term neonates born between January 1995 and December 1999 in the study
population. Babies born by elective caesarian section and babies with
congenital malformation were excluded. Birth during 9 P.M. and 9 A.M. was
defined as birth during night Amongst 9460 eligible babies, 5071(53.6%)
were born during day and 4389(46.4%) were born during night. There was no
difference in the mode of delivery during day and night. Incidence of
maternal complications that predisposes for perinatal asphyxia was 15%
among the babies born during the day and it was 16.2% among the babies
born during the night. The incidence of early neonatal mortality was 11.4
per 1000 livebirths and 6.5 per 1000 livebirths among the babies born
during the night and day respectively (relative risk = 1.75 [95% CI = 1.11
-2.80]). The incidence of birth asphyxia related deaths was 8 per 1000
livebirths and 4.5 per 1000 livebirths among the babies born during the
night and day respectively (relative risk = 1.76 [95% CI = 1.04-2.97]).
Our results further support the finding of the earlier studies.1,2,3
We included the morning hours upto 9AM in the definition of night because
the duty of the staffs changes at 8AM and during this period usually the
care of the patients suffer as the tired staffs are in hurry to leave the
hospital and the new staffs take some time to go through the ongoing
management. We have a much higher neonatal mortality due to the various
factors, particularly the late referral of mothers and hence more moribund
patients. Considering the results of higher mortality among the babies
born during the night time, the hospital administration should come out
with novel ideas to increase the efficiency of the staffs during the night
duty hours.
References:
1. Heller G, Misselwitz B, Schmidt S. Early neonatal mortality, asphyxia
related deaths, and timing of low risk births in hesse, Germany, 1990-8:
observational study. BMJ 2000;321:274-75.
2. Stewart JH, Andrews J, Cartlidge PHT. Numbers of deaths related to
intrapartum asphyxia and timing of birth in all Wells perinatal survey,
1993-5. BMJ 1998;316:657-60.
3. Chalmers JWT, Shanks E, Paterson S, McInneny K, Baird D, Penny G.
Scottish data on intrapartum related deaths are in same direction as Wells
data. BMJ 1998;317:539.
Competing interests: No competing interests
Dear Editor
The unstated premise of the article by Heller et al1 that the incidence of
perinatal death due to intrapartum asphyxia in low risk pregnancies may
serve as a sensitive measure of the quality of peripartum care delivered
is appealing 2. However the proposition by Heller that the observed higher
nocturnal perinatal mortality in a selected population was a result of
substandard care was not justified in the article.
Firstly, a comprehensive index case record interrogation was absent.
The Confidential Enquiry in to Stillbirths and Deaths in Infancy (CESDI) 3
adopts the gold standard method of a multi-disciplinary scrutiny of the
records to ensure diagnostic accuracy as well as quantification of any
substandard care involved.
Secondly, imprecise selection criteria ensured the sample population
was heterogeneous in terms of pregnancy risk and method of delivery.
Further bias arose as Heller’s early neonatal death rate (0.15 per 1000
births selected) represented only a small fraction of the unstated overall
early neonatal death rate (3.1 per 1000 live births found in a similar
population by CESDI 2).
Thirdly, recommended criteria necessary before a diagnosis of acute
perinatal asphyxia can be made 4 were not adopted by Heller’s article.
Furthermore it is noteworthy that deaths classified as ‘asphyxia related’
occurring as a result of hypoxia during labour do not necessarily mean
that the hypoxia was preventable.
More useful information would have been derived if the crude early
neonatal death rate data were reclassified in a pathophysiological cause-
specific manner e.g. adopting the amended Wigglesworth classification 5 or
incorporated birth weight/gestation specific mortality. Such cause-
specific mortality relationships better identify the exact contribution of
antepartum and intrapartum risk factors to infant mortality and whether
there is any diurnal variation to their incidence. Importantly, Heller’s
article could not demonstrate whether high-risk pregnancies present more
frequently at night. Case-control analysis of matched cases with similar
obstetric-neonatal factors and delivery centres but differing by delivery
time could further reveal the contribution of delivery time to perinatal
death and whether this relationship is cause-specific.
Ultimately the identification of pregnancies without substandard care
or obstetric risk that still incur a significantly higher nocturnal
perinatal mortality pose a serious concern which perhaps represents a
manifestation of the maternal-fetal physiology specific to this period
which at present is unknown. Antepartum "unexplained" fetal death might
also enter into this subgroup, which, despite advances in obstetric
medicine and fetal monitoring, comprises the majority of perinatal deaths.
Standards of health care delivery are always under inspection (e.g.
Clinical Governance, the media) and thus comprehensive evaluation, with
consideration given to other possible causes, is essential before such
‘human’ issues are drawn into the causality equation for adverse outcome
occurring at night.
Yours sincerely
Rajesh Varma MA MRCOG DFFP
Senior SHO Obstetrics and Gynaecology
Srinivas Vindla MD MRCOG
Specialist Registrar Obstetrics and
Gynaecology
Lawrence Mascarenhas MD MRCOG M.Ed
Consultant Obstetrician and
Gynaecologist
Department of Obstetrics and Gynaecology, Queens Medical Centre,
Nottingham, NG7 2UH
E-mail DrRajesh@varma16.freeserve.co.uk
References
1. Heller G, Misselwitz B, Schmidt S. Early neonatal mortality, asphyxia
related deaths, and timing of low risk births in Hesse, Germany, 1990-98:
observational study. BMJ 2000; 321: 274-5
2. Field DJ, Smith H, Mason E, Milner AD. Is perinatal mortality still a
good indicator of perinatal care? Paediatr Perinat Epidemiol 1988; 2:213-9
3. Confidential Enquiry into Stillbirths and Deaths in Infancy. Sixth
Annual Report. London: Maternal and Child Health Research Consortium. 1999
4. American Academy of Pediatrics, American College of Obstetricians and
Gynecologists. Relationship between perinatal factors and neurologic
outcome. In: Poland RL, Freeman RK, editors. Guidelines for perinatal
care. 3rd ed. Elk Grove Village (IL): American Academy of Pediatrics;
1992.pp 221-4.
5. Keeling JW, MacGillivray I, Golding J, Wigglesworth J, Berry J, Dunn
PM. Classification of perinatal death. Arch Dis Child 1989; 64: 1345-1351
Competing interests: No competing interests
Pregnancy Institute has published an observation on nighttime fetal
death in the American Journal of Obstetrics and Gynecology and with the
Royal College of Obstetricians and Gynecologists "The Placenta " Placenta
Study Group 2000. Our working theory is based on >300 interviews with
mothers with umbilical cord related stillbirth. Occuring on the average at
38 weeks, all stillbirths took place during maternal sleep (between 12mn-
7am). The possible explanation is maternal blood pressure declines during
sleep. A stressed fetus may be vulnerable to the uterine ischemia and
braxton hicks contractures which result. Those fetuses which enter labor
may be already compromised from days of stress prior to hospitilization.
There are previously published works which have observed nightime and
weekend differences in fetal death. Maybe it is not just a personnel
factor but a fetal predisposition. It may be important for CESDI to look
closely at "time of death".
Jason H Collins M.D. Pregnancy Institute
Competing interests: No competing interests
The authors say that they "excluded caesarean sections". I can
understand the rationale for excluding elective caesareans, but I think it
would be important to include emergency caeasarean sections, especially
those done for suspected fetal compromise. I appreciate that the the same
exclusion criteria applied to the day time population as to the night time
one- but there could still be imbalances with this exclusion criterion.
Competing interests: No competing interests
With respect to the higher infant mortality
rate of night birthed babies, it would seem as
important or more important the fatigue level of the
mother as the fatigue level of the doctors delivering
the baby. If the birthing mother's biological clock is
set to be at sleep during the night as usual, the
birthing mother will be weaker during the day than at
night. The solution to this may be in some cases to
induce birth during the day or at a time when it is
determined that the mother is strongest on her
biological sleep clock. Of course, if there is a
problem with induced births than with noninduced
births then this may not be wise to take the risk of
inducing a birth. Inducing such a birth of course
would only be done within 12 hours of the expected
birth itself of course, such that if it was determined
that the birth could fall into a nightime period of
time, it might be induced during the daytime within a
short period of time, provided the inducement
procedure itself was safe. This simply might involve
some kind of focussed sonic pricking of the uterine
sack to permit the mother's "water" to break, so long
as it was so localized a sonic puncturing that it did
not disturb the prenatal infant.
These are my opinions. I am not a medical doctor.
Any use of such methods would require the proper
review and testing of such methods for their utility
and safety to the mother and infant.
Competing interests: No competing interests
Reply to e-letters 1 to 4
Editor: In the following we would like to respond to the e-letters
referring to our short report:
1.) Excluding all caesarean sections instead of elective caesarean
sections only (James King)
The database we used contains an item which indicates whether a
primary (elective) section or a secondary (emergency) section was
performed. However, due to previous validation of the database we knew
that the distinction between primary and secondary caesarean section was
interpreted differently by the obstetricians documenting the births.
We therefore used a straightforward approach and excluded all
caesarean sections.
2.) Mothers fatigue may be also important (Donald Fraser Miles)
Interestingly the comments given by Donald Fraser Miles seem very
similar to those written by medical professionals when commenting on
alternative explanations for the circadian mortality gradient. Therefore
our comments given to alternative explanations towards the end of our
reply may also serve as answers to the comments by Mr. Miles. The main
difference to the comments of medical professionals seems to be that Mr.
Miles also considers induction of births as an alternative strategy to
reduce excess neonatal mortality at night. At this point we would simply
like to add that the discussion of planing the timing of birth (programmed
birth) is not new in obstetrics (1,2). We agree with Donald Fraser Miles
that this alternative would need careful evaluation before making use of
it.
3.) Night time fetal death and maternal sleep (Jason Collins)
We appreciate the perinatal physiologic speculations of Dr. Collins
as well as the reference to his own scientific work (3). Unfortunately
almost all of his remarks refer to "fetal death" which was not the subject
of our analyses. As noted in our paper we did not analyse stillbirths but
deaths during labour and in the first week after birth. We therefore
excluded all infants deceased before birth, all deaths for whom the time
of death was not known as well as those who died before arrival to the
birth clinic. We have performed additional analyses with time of death as
predictor, or stillbirths as endpoint without observing a circadian
mortality gradient within our data so far. These results may be seen as an
argument against Dr. Collins hypotheses that reduced maternal blood
pressure resulting in births of previously compromised fetuses can mainly
be assumed to have caused early neonatal deaths analysed for this article.
Additionally it is not clear how the mechanism proposed by Dr.
Collins may be an explanation for the increased weekend mortality he
refers to.
4.) Other causes predisposing to increased night-time perinatal
mortality have not been excluded (Rajesh Varma et al.)
In their first point they argue a comprehensive index case record
interrogation was absent in our data and describe in the following the
advantages of the Confidential Enquiry into Stillbirths and Deaths in
Infancy (CESDI) (4). Like presumably anyone else we agree that the CESDI
has several serious advantages compared with our data. Nevertheless our
data/ results indicate an excess early neonatal mortality at night. Varma
et. al.'s first point contains no serious argument why our results should
be biased in any specific direction.
Despite this fact Varma et al. try to imply they had already shown
our results were biased by referring to our selection criteria in their
second point ("further bias arose"). We would appreciate it if further
discussion by Varma et al. or by others referring to this important topic
would not rely on such merely rhetoric arguments.
Varma et al. criticise that our selection criteria are too imprecise.
They are however much more precise than the ones in the British studies we
referred to (5,6) and were even more precise in earlier drafts of our
paper. We therefore wonder why Varma et al. failed to comment on these
reports published just two years ago, especially as the results of those
studies seem to be much more relevant to them: Both refer to British
populations and to a health system they are currently working in.
Furthermore Varma et al. complain our early neonatal death rate is
too low which means nothing more that our selection criteria is too
rigorous. In our article we had however explained why we applied the
selection criteria used in our analysis: "There was some concern, that
babies born during daytime are more likely preterm or high risk babies who
have had induced births. We therefore restricted our study population
rigorously". In fact it is an easy task to demonstrate that this is the
case. Therefore our selection criteria is more likely to avoid bias than
to produce it. Unfortunately again Varma et al. failed to follow this
important argument when commenting our article.
In their third point Varma et al. repeat an argument they had already
presented within their first point, this time referring especially to the
diagnosis "asphyxia related deaths".
Hereby it is important to mention that we had already critically discussed
exactly this topic in our short report, but we added: "Nevertheless a
higher early-neonatal mortality in general and a higher mortality related
to asphyxia was seen". Once more it is unclear why Varma et al. are
unwilling to take our discussion of this topic into account, when
commenting our article.
In the same paragraph the authors state that not all hypoxia during
birth were preventable.
We agree and would like to add that further assumptions have to be made
before it can be assumed that excess deaths at night are not or less
preventable. Additionally we would like to note that Varma et al. give no
conclusive hint why hypoxia should be less preventable at night than
during daytime.
In the following paragraph Varma et al. offer several advises how our
article could have been improved. First they refer again to the
classification of death and recommend reclassification into the amended
Whigglesworth classification (7,8). Unfortunately Varma et al. do not seem
to know our data-set as well as we knew the Whigglesworth classification
when writing our paper. In fact we have tried to perform exactly this
reclassification but had to realise that this would produce very critical
results as the classifications used are too different. As the diagnosis
was additionally based only on the obstetrician in charge of the birth we
decided not to focus our analyses so much on the diagnosis given and more
on the total numbers of death during the early neonatal period.
Varma et al. recommend usage of several additional methods, which all
aim at ruling out or assessing the effect of other explanatory factors
than decreased medical care at night on the observed early neonatal
mortality gradient, e.g. controlling for the hypothetical fact that excess
neonatal deaths were to a substantial amount result of a higher frequency
of "high risk pregnancies at night". As several other comments refer to
almost identical topic, we would like to comment on them together:
James Collins suggested a lowered maternal blood pressure during the
night in previously compromised fetuses as a possible causal factor,
increased pregnancy risk of night births have been previously discussed
e.g. by Murphy (9) or Ruffieux et al. 1992 (10).We agree that this is an
important topic. In the letter accompanying the first draft of our paper
we wrote that we submitted the paper as a short report as we expected the
interest of the BMJ in German data confirming previous British analyses
would not be sufficient to give us room for a normal paper. We added that
we were willing to provide additional information/ analyses if requested
and have tried to do so in the following first revision of our paper but
were then advised to cut it out in order not to exceed the word limit,
which we were told to be interpreted in a strict sense. It is common sense
that a paper of a maximum of 600 words necessarily leaves many questions
open. (The comments on our paper currently count 917 words). Since the
submission of the first draft of our paper in January 2000, we have
nevertheless extended our database, performed additional detailed analyses
taking alternative risk factors of nocturnal early neonatal mortality into
account as well as written a new article, which we will submit within the
next weeks.
Other meanwhile published data by Kumar
(http://www.bmj.com/cgi/eletters/321/7256/274) confirmed a circadian
gradient of early neonatal mortality without detecting remarkable
differences in maternal complications predisposing for perinatal asphyxia.
Additionally, the response of Westgate and Gunn may be interpreted as
pointing into a similar direction.
It has to be kept in mind, however, that we are dealing with
observational studies. No evidence in the strict meaning of the word can
be expected from these kind of studies. Even after performing additional
and more detailed analyses it is common sense that alternative not
necessarily mutually exclusive explanations (11) will still be discussed
or cannot be completely ruled out.
The only alternative to provide such evidence would be conducting a
randomised clinical trial. However, such a trial would be very difficult
to perform. Very large numbers would have to be included and even more
important a randomisation into a high and low care group will be very
likely to be regarded as unethical. Maybe if Varma et al. were members of
an ethical committee would decide that such a trial is ethical to perform;
we would not.
Therefore, knowing the results of our currently unpublished analyses,
we believe it is justified to consider "better designed shifts, resulting
in shorter working hours or decreased workload with greater supervision by
experienced staff at night (...) to reduce early neonatal mortality during
the night" (12).
Yours sincerely
Günther Heller, MD
Björn Misselwitz, MD
Stephan Schmidt, MD
References:
(1) Wulf KH. Die programmierte Geburt. Therapeutische Umschau
1981;38:1009-1014.
(2) Maslow AS, Sweeney AL. Elective induction of labor as a risk
factor for cesarean delivery among low-risk women at term. Obstet Gynecol
2000;95:917-922
(3) Collins JH. Umbilical cord accidents--time of death? Am J Obstet
Gynecol 1997;177: 1566
(4) Confidential Enquiry into Stillbirths and Deaths in Infancy.
Sixth Annual Report. London: Maternal and Child Health Research
Consortium.1999
(5) Stewart JH, Andrews J, Cartlidge PHT. Numbers of deaths related
to intrapartum asphyxia and timing of birth in all Wales perinatal survey.
1993-1995. BMJ 1998;316:657-660
(6) Chalmers JWT, Shanks E, Paterson S, McInneny K, Baird D, Penney
G. Scottish data on intrapartum related deaths are in same direction as
Welsh data. BMJ 1998;317:539
(7) Keeling JW, MacGillivray I, Golding J, Wigglesworth J, Berry J,
Dunn
PM. Classification of perinatal death. Arch Dis Child 1989;64:1345-1351
(8) Patrick H T Cartlidge, Andrew T Dawson, Jane H Stewart, Gordan M
Vujanic.
Value and quality of perinatal and infant postmortem examinations: cohort
analysis of 400 consecutive deaths. BMJ 1995;310:155-158
(9) Murphy DJ. Denominators are needed before conclusions can be
drawn. BMJ 1998;316:1318
(10) Ruffieux C, Marazzi A, Paccaud F. The circadian rhythm of the
perinatal mortality rate in Switzerland. AJE 1992;135:936-952
(11) Macfarlane A. Variation in number of births and perinatal
mortality by day of week in England and Wales. BMJ 1978(2):1670-1673
(12) Heller G, Misselwitz B, Schmidt S. Early neonatal mortality,
asphyxia related deaths, and timing of low risk births in Hesse, Germany,
1990-8: observational study. BMJ 2000;321:274-275
Competing interests: No competing interests