uog journal club: poor neonatal acid–base status in term fetuses with low cerebroplacental ratio...

UOG Journal Club: February 2015

Poor neonatal acid–base status in term fetuses with low

cerebroplacental ratio

J. Morales-Roselló, A. Khalil, M. Morlando, A. Bhide, A. Papageorghiou

and B. Thilaganathan

Volume 45, Issue 2, Date: February (pages 156–161)

Human fetal growth is constrained below optimal for perinatal

survival

B. Vasak, S.V. Koenen, M.P.H. Koster, C.W.P.M. Hukkelhoven, A. Franx,

M.A. Hanson and G.H.A. Visser


Journal Club slides prepared by Dr Aly Youssef

(UOG Editor for Trainees)


Poor neonatal acid–base status in term fetuses with low

cerebroplacental ratio

J. Morales-Roselló, A. Khalil, M. Morlando, A. Bhide, A. Papageorghiou

and B. Thilaganathan


Introduction

• Term fetuses with birth weight above the 10th centile are labeled

appropriate for gestational age (AGA)

• Although AGA fetuses are considered to be healthy, it is

accepted that some of them may suffer from placental

insufficiency and fail to reach their genetic growth potential

• A potentially useful approach to detect AGA fetuses at increased

risk of adverse pregnancy outcome is the use of the

cerebroplacental ratio (CPR) to suggest placental insufficiency

and failure to reach their growth potential (FRGP), regardless of

their absolute birth-weight centile

Poor neonatal acid–base status in term fetuses with low cerebroplacental ratioMorales-Roselló et al., UOG 2015

To evaluate to what extent arterial and venous umbilical

blood pH at birth are associated with birth weight

and fetal CPR

Aim of the study


• This was a retrospective cohort study in two tertiary centers, including

singleton term fetuses that underwent an ultrasound scan within 14 days of

delivery.

Methods

• The umbilical (UA) and fetal middle cerebral (MCA) arteries were examined

using color Doppler ultrasound

• CPR was calculated as the ratio between the MCA and UA pulsatility

indices (PI)

• Birth weights were converted into centiles, and CPR values were converted

into multiples of the median (MoM), correcting for gestational age


• A pregnancy with a fetal CPR below 0.6765 MoM was considered more

likely to have placental insufficiency (also labeled as failure to reach growth

potential; FRGP)

• The acid–base status represented by the arterial and venous

umbilical cord pH obtained at birth was correlated with CPR and

birth weight using scattergrams, calculating the correlation

coefficient r² and P-value.

Subsequently, arterial and venous pH were compared between the

subgroups with and without low CPR

• Large for gestational age (LGA) was defined as birth weight > 90th

percentile, small for gestational age (SGA) was defined as birth

weight < 10th percentile and AGA was defined as birth weight

between the 10th and 90th percentiles


Methods

Results: correlation between birth weight and neonatal blood pH

There was a significant

correlation between birth

weight and venous-blood pH

(r2 = 0.005, P < 0.001),

but not between birth weight

and arterial-blood pH

(Figure; r2 = 0.001,

P = 0.180)


Solid lines represent best fit with linear regression; dashed lines are 95% confidence intervals

Results: correlation between CPR and neonatal blood pH

CPR was significantly

correlated with both arterial-

blood and venous-blood

pH (r2 = 0.008, P < 0.0001 and

r2 = 0.01, P < 0.0001,

respectively)


Solid lines represent best fit with linear regression; dashed lines are 95% confidence intervals

Results: blood pH in neonates with abnormal (FRGP) and normal CPR

• The AGA and LGA subgroups with normal CPR had higher arterial- and

venous-blood pH than did their respective subgroups with low CPR

• No significant differences were found in the SGA subgroups with and without

abnormal CPR


• This study demonstrates that at term, fetal CPR is better correlated with

umbilical cord blood pH than it is with birth weight

• AGA fetuses with low CPR presented with significantly lower neonatal

pH than AGA fetuses with normal CPR

• Identifying fetuses with placental insufficiency near term is challenging,

as the baby has usually already attained a good weight.

• The data of this study support the assertion that CPR may be just as

good at predicting AGA fetuses at risk of compromise as it is at

predicting SGA fetuses at risk

• This finding may be of value in risk assessment for stillbirth at term and

long-term neurodevelopmental disability

Discussion


Weaknesses

• Retrospective design; however this limitation is mitigated to a

certain extent by the size of the population studied and the

prospective data collection of fetal Doppler indices and

umbilical cord blood pH

• Umbilical cord blood pH at birth is likely to be influenced by

multiple maternal characteristics and intrapartum confounders


Discussion points

• How should women at term with AGA fetuses and low CPR be

managed?

• Which cut-off value for CPR should be used to define fetal blood flow

redistribution?

• Should middle cerebral artery and umbilical artery measurements be

performed routinely in women with AGA fetuses?

Future studies are needed to evaluate the performance of the CPR in

AGA fetuses in the prediction of perinatal mortality and neonatal

neurodevelopmental impairment, with the aim of optimizing the timing

of delivery and reducing perinatal complications and long-term

neonatal handicap

Future perspectives



Human fetal growth is constrained below optimal

for perinatal survival

B. Vasak, S.V. Koenen, M.P.H. Koster, C.W.P.M. Hukkelhoven,

A. Franx, M.A. Hanson and G.H.A. Visser


• Use of fetal growth charts assumes that optimal size at birth is at

the 50th birth-weight centile

• However, the interaction between maternal constraints and risks

associated with small and large fetal size at birth may indicate that

this assumption is not valid for perinatal mortality rates

• Indeed, it is believed that human fetal growth is constrained

below its genetic potential in all pregnancies, to a greater or lesser

degree, to match size at birth to maternal physical characteristics

• However, this optimal size assumption has not been examined in

a sufficiently large contemporary population in a high-income setting

to describe this aspect of human biology.

Background

Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015

To investigate the distribution and timing of perinatal

mortality and morbidity in relation to birth weight and

gestational age at delivery

Objective


• This was a retrospective population-based cohort study including data

collected from the Netherlands Perinatal Registry on 1 170 127 births that

delivered between 28–43 weeks’ gestation from singleton pregnancies

between 2002–2008

• Children with congenital abnormalities were excluded

• Birth weight was displayed in centile groups

Data analysis


• Distribution of perinatal mortality according to birth weight was studied

• Mortality rates were subdivided in to antepartum, intrapartum and neonatal

death to assess these relationships separately for the different time periods

of occurrence of death

• The relationship between perinatal mortality, birth weight and gestational

age at delivery was studied

Methods

Results

• Among 1 170 534 singleton fetuses included in the study period,

there were 5075 (0.43%) perinatal deaths

• 54% of all perinatal deaths occurred ≥ 37 weeks’ gestation

• 29% of the perniatal deaths occurred in infants with birth weight

< 10th centile, but 64% in infants with a weight between the 10th

and 90th centiles, with a similar distribution at all gestational ages



Perinatal mortality according to birth-weight centiles

• The incidence of perinatal death was highest in those with a

birth weight below the 2.3rd centile (25.4/1.000 births),

falling gradually with an increasing birth weight up to the

80th and 90th centiles, at which the lowest death rates

occurred

• Perinatal mortality of infants with a birth weight between the

80th–90th centile was significantly lower than that of infants

with a birth weight between 50th–80th centile or ≥ 90th centile

(chi square test; P = 0.02 and 0.004, respectively)

Results: antepartum, intrapartum and neonatal deaths

• Antepartum deaths accounted for 72% of all perinatal

deaths and were lowest in infants of birth weight

between the 90th and 95th centiles

• Intrapartum and neonatal deaths were lowest between

the 80th and 84th centiles

• The same patterns were found when data were

restricted to infants born ≥ 37 weeks of gestation, or to

those born between 39 and 40 weeks


Results: perinatal mortality and gestational age

Perinatal

mortality

decreased as

gestational

age

progressed for

all groups


• This study shows that, from an immediate survival perspective,

optimal fetal growth requires a live birth weight between the 80th to

90th centile

• Median birth weight in the population is by definition substantially

lower, implying that the majority of fetuses exhibit some form of

maternal constraint of growth

• The finding that lowest perinatal mortality and morbidity is not

present in infants with a birth weight around the 50th centile, but at a

much higher centile, raises important issues about human

development

• These findings may represent the adaptations evolved in humans,

in conjunction with large head size and bipedalism, to reduce the

risk of obstructed delivery

Discussion


Limitations

• Lack of information on the cause of death

• Possible inaccuracies in discriminating between antepartum and

intrapartum deaths

• The use of customized growth charts might have refined the data,

but such information is not present in The Netherlands Perinatal

Registry

• Large population size, with data from The Netherlands Perinatal

Registry containing approximately 95% of all births in The

Netherlands

Strengths


Discussion points

• Are the present definitions and centiles accurate for

identifying fetuses with inadequate intrauterine growth?

• Should other instruments (e.g. cerebroplacental ratio)

be integrated routinely in to the assessment of fetal

growth at or near term?


uog journal club: poor neonatal acid–base status in term fetuses with low cerebroplacental ratio...

Health & Medicine

aga fetuses

singleton term fetuses

introductionterm fetuses

cerebroplacental ratio

low cerebroplacental

uog journal club

low cprlarge

birth weightand fetal