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UOG Journal Club: Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio and Human fetal growth is constrained below optimal for perinatal survival

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UOG Journal Club: Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio and Human fetal growth is constrained below optimal for perinatal survival

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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)
http://onlinelibrary.wiley.com/doi/10.1002/uog.14647/abstract

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
Volume 45, Issue 2, Date: February (pages 162–167)
http://onlinelibrary.wiley.com/doi/10.1002/uog.14644/abstract

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)
http://onlinelibrary.wiley.com/doi/10.1002/uog.14647/abstract

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
Volume 45, Issue 2, Date: February (pages 162–167)
http://onlinelibrary.wiley.com/doi/10.1002/uog.14644/abstract

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UOG Journal Club: Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio and Human fetal growth is constrained below optimal for perinatal survival

  1. 1. 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 Volume 45, Issue 2, Date: February (pages 162–167) Journal Club slides prepared by Dr Aly Youssef (UOG Editor for Trainees)
  2. 2. 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)
  3. 3. 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 ratio Morales-Roselló et al., UOG 2015
  4. 4. 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015
  5. 5. • 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015 • 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)
  6. 6. • 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015 Methods
  7. 7. 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) Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015 Solid lines represent best fit with linear regression; dashed lines are 95% confidence intervals
  8. 8. 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) Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015 Solid lines represent best fit with linear regression; dashed lines are 95% confidence intervals
  9. 9. 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015
  10. 10. • 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015
  11. 11. 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015
  12. 12. 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 Poor neonatal acid–base status in term fetuses with low cerebroplacental ratio Morales-Roselló et al., UOG 2015
  13. 13. UOG Journal Club: February 2015 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 Volume 45, Issue 2, Date: February (pages 162–167)
  14. 14. • 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
  15. 15. To investigate the distribution and timing of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery Objective Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  16. 16. • 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 Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015 • 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
  17. 17. 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 Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  18. 18. Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015 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)
  19. 19. 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 Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  20. 20. Results: perinatal mortality and gestational age Perinatal mortality decreased as gestational age progressed for all groups Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  21. 21. • 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 Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  22. 22. 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 Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015
  23. 23. 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? Human fetal growth is constrained below optimal for perinatal survival Vasak et al., UOG 2015

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