Cerebroplacental Ratio ( CPR) as Screening Test

for Respiratory Morbidity with Diabetes Mellitus

Moreno Uribe N, Romero Nava Rodrígo, Juan Carlos Hinojosa Cruz, Mary Flor Díaz
Velázquez, Amado Miranda Rodríguez, Antonio Helue Mena
 • 2nd /3er Trimester
• 75-g oral glucose-tolerance testing at 24 to 32
Gestational weeks of gestation. Considered diagnosis if the
plasma glucose level was:
Diabetes  Fasting 92 mg/dl (5.11mmol/l)
 1 hr 180 mg/dl (9.99mmol/l)
 2 hr 153 mg/dl (8.49mmol/l)

Diabetes Mellitus • FPG > 126 mg/dl ( 7.0mmol/L)

• 2HPG > 200 mg/dl (11.1mmol/L) with 75 g
(Pre- gestational) anhydrous glucose disolved in water.
• AIC> 6.5% (48 mmol/mol)
Type 1 • Classic symptoms of hyperglycemia or
hyperglycemic crisis or a random plasma glucose >
200 mg/dl (11.1 mmol/L)
Type2

𝐼𝑛𝑐𝑟𝑒𝑎𝑠𝑖𝑛𝑔 𝑃𝑟𝑒𝑣𝑎𝑙𝑒𝑛𝑐𝑒
Pregnancy and Diabetes Up to 13% of women
HAPO Study. 2008

25,505 women 15 centers 9

countries
• Load 75 grams of anhydrous glucose
• 24-32 weeks

Primary Outcomes

Large for gestational

age Clinical Symptoms of C Peptide > 90 centile Preterm Birth
Hypoglicaema 2.1% : 90 8.4% (<37sem) 1.3%
9.5%

Obstetric Trauma: Hyperbilirrubinaemia

NICU admission 8.0%
1.3% 8.3%
Respiratory Morbidity in newborns exposed to Diabetes in
pregnancy

OR 8.28 (IC 95% 5.90-11.6)

Fetal Haemodynamics. Pulsatility Index and Cerebroplacental
Ratio

PICMA
CPR=
PIUa

Cafici, D. (2007) Ultrasonido Doppler en Obstetricia. Editorial Journal.

Fetal Haemodynamics

• Brainsparing
↓PI event.
• Under response
CMA to hypoxia

• Higher placental
↑ resistency
• 30% loss of

PIUa placental
function

Cafici, D. (2007) Ultrasonido Doppler en Obstetricia. Editorial Journal.

REGULATION OF CEREBRAL FLOW

Autoregulation CBF=AP-ICP
CVR
of Cerebral Flow
CBF= Cerebral blood flow AP= Arterial
pressure ICP= Intracraneal pressure CVR=
Cerebrovascular resistance

CO2 Sensitive

Roy CS, Sherrington CS. On the regulation of the blood-supply of the brain. J Physiol. 1890;
85–158
Hall CN, Reynell C, Gesslein B, et al. Capillary pericytes r regulate cerebral blood flow in
health and disease. Nature. 2014; 55–60.
Ainslie PN, Duffin J. Integration of cerebrovascular CO2 reactivity and chemoreflex control
of breathing: mechanisms of regulation, measurement, and interpretation. Am J Physiol
Regul Integr Comp Physiol. 2009; 1473–1495.
Hyperglycaemia? Somers K, Mark A, Zavala D, et al. Contrasting effects of hypoxia and hypercapnia on
ventilation and sympathetic activity in humans. J Appl Physiol. 1989; 2101–2106.
Zappe A, Uludaǧ K, Oeltermann A, The influence of moderate hypercapnia on neural
activity in the anesthetized nonhuman primate. Cereb Cortex. 2008; 2666–2673.
CPR in Term Pregnancies

Outcome García Belido Trieunfo Figueras Prior

Simón González 2016 2015 2015
2015 2016 Heterogeneous
Weeks of >37 >37.1 >37 Groups
gestation
Estimated LGA IUGR All LGA LGA
fetal weight
(N) 164 120 946 509 775
Abnormal 89 32 NR 200 284
CPR Different cut- off
Set point <0.6765 < P5th Z score < P5th <0.676 points
MoM <7days 5
MoM
Days between < 14 days < 7 days NR < 24 hrs < 72
USG – Birth hrs

Blinded Yes NR Yes Yes NR Controversial

Low Apgar 49.0% vs Results
33%
Acidosis at 11.2%
birth vs6.7%
Admision to 14.3% vs 21.9% vs NS 2%
NICU 9.7% 11.1% vs 1.8% Diagnostic cut- off
point may differ
Composite 37.5% vs
depending of the
outcome 19.1% selected population
CPR in Diabetes

Author (year) Selected Maneuver

Populationn Outcomes
Study Type
1089 fetuses CPR Low Apgar,
G1: <P10
34-36 weeks with Hypoxia Compound Perinatal Outcome
Gestational G2: P 11- ORa 2.93 (IC 1.95-4.40)
Diabetes 89 NICU Admission
Gibbons (2017) Respiratory Distress Syndrome
G3 > P 90 Respiratory Distress (OR 1.93 IC 1.52-165)

Retrospective Hypoglycaema

Perinatal Death
Aim

To evaluate the Sensibility and Specificity of

CPR as a screening test of respiratory
morbidity** in term pregnancies with
Diabetes .

*** Transient Newborn Tachypneea, Respiratory Distress Syndrome or suplementary

O2 need
Term Pregnancies with Any Respiratory Morbidity with
Type of Diabetes Diabetes Mellitus
(Type 1, Type2 or Cerebroplacental Index Any of: Transient Newborn
Gestational) Tachypneea, Respiratory
Distress Syndromee or
suplementary O2 need

Diagnostic Demarcation Prognostic Status

•Universe : Mexican Institute of Social Security Users
•Diagnostic Criteria: •Status: Diabetes Type (Type 1, Type 2, Gestational Diabetes)
•ADA 2018, HAPO 2008 Metabolic Control (HbA1c < 6.5%)
•Term Pregnancies: (37/0 - 41/6) weeks)
•Exclusion Criteria • Clínical 1. I Nutritional Pregestational Status (Clasification by Body
• Associated morbidity (Hypertension, Renal Dissease, Thyroid Dissease, Mass Index)
Autoinmunne Dissease)
• Suspicion of fetal anomalies •Clínical 2. Ponderal Gain (kg)
• Multiple Pregnancy
• Denial to participate •Clinical 3. Fetal Weight
•Elimination Criteria
• Delivery in other hospital •Other maneuvers: Type of Treatment used to get diabetes control
• Delivery ocurrs more than after 7 days from the doppler ultrasound
• Newborn detection of anomalies
• Preeclampsia, HELLP Syndrome or Placental Abruption.
• Ultrasound Suspicion of dilated myocardiopathy.
Results:
Figure 1. Diagram Flowchart

205 patients
were invited to participate

10 denied participation
2 had probable fetal
anomalies

193 patients
were selected for CPR
meassurement

4 patients were eliminated:

2 delivery in an other hospital
1 delivery after 7 days
1 developed abruptio placentae

189 patients
were included in the
analysis
Table 1. General Characteristics
General Caracteristics
*
Age (years) 31 (18-46)
*
Pre-pregnancy weight (Kg)* 70 (42-109)
¥
Pre-pregnancy BMI (Kg/m2) 28.8 (+/- 5.23)
Clasification of BMI
£
Normal (< 24.9 mg/kg) 46 (24.2%)
£
Overweight (25.0- 29.9 mg/kg) 63 (33.2%)
£
Obese (>30 mg/kg 81 (42.6%)
¥
Actual weight (Kg)- 79.35 (+/- 12.49)
*
Evolution time (Weeks)* 14 (+/- 1078)
*
Gestational age at (Weeks)* 38.3 (37-41)
ultrasound
*
Fetometry (Weeks)* 37.6 (35-40)
*
Fetal weight (Kg)* 3423 (2035-3828)
*
HbA1C (%)* 5.7 (5-7)
*
Weight gain (Kg)* 8 (<17-25)
£
Smoking (Positive) 4 (2.1%)
£
Alcoholism (Positive) 1 (0.5%)
£
Type of diabetes Type 1 3 (1.6%)
£
Type 2 35 (18.4%)
£
Gestational 152 (80%)
£
Type of treatment Diet 103 (54.2%)
£
Diet + oral hypoglycemic 50 (26.3%)
£
Diet + insulin 37 (19.5%)
£
Fetal gender Men 13%
£
Women 83%
£
Metabolic control (%)) 158 (83.2%)

£ Cualitative variables are described in percentages and frecuencies. * Cuantitative variables with non parametric
distributions are described with median and minimum and maximum ranges. ¥ Cuantitative variables with parametric
distribution are described with median and standard distribution
Figure 1. ROC Curve analysis showing the clinical performance
< 13th for respiratory morbidity in term pregnancies with
Diabetes Mellitus

Sensibility: 95.4% (75.1-99.7%)

Specificity: 74.8% (67.4-81.0%)
PPV: 33.33% (22.2-46.4%)
NPV: 99.21%(95.0-99.9%)
LR+: 3.8 (2.8-5.0)
LR-: 0.06 (0.01-0.41)
Table 1.5 General Characteristics divided by brainsparring

Brainsparring Without Brainsparring p

CPR (<13
n=63 n=126
Age (years) 31 (20-46) 31 (18-42) 0.840
Pre-pregnancy weight (Kg) 74 (49-100) 70 (42-109) 0.880
Pre-pregnancy BMI * (Kg/m2) 28.5 +/-5.09 29.01 +/- 5.31 0.416
BMI Clasification
Normal 18 (28.1%) 28 (22.2%) 0.127
Overweight 15 (23.4%) 48 (38.1%)
Obese 31 (48.4%) 50 (39.7%)
Actual weight * (Kg) 80.8 +/- 12.3 78.5 +/- 12.5 0.772
Weight gain (Kg) 8 (1-22) 8 (-17-25) 0.294
Evolution time (Weeks) 18 (1-780) 12 (1-1078) 0.015
Gestational age at ultrasound (Weeks) 38.3 (37-40) 38.2 (37-41) 0.996

Fetometry (Weeks) 38.0 (37-40) 37.6 (37-40) 0.425

Fetal weight (Kg) 3434 (2035-3828) 3380 (2784-3846) 0.692
HBa1C (%) 5.7 (5-7) 5.6 (5-7) 0.065

Smoking 1 (1.6%) 3 (2.4%) 1.0

Alcoholism 1 (1.6%) 0 (0%) 0.098

£ Cualitative variables are compared wit X2* Cuantitative variables with non parametric distributions are compared using U Mann Whitney. ¥ Cuantitative
variables with parametric distribution are compared using Studen T Test. P value considered statistically significative is <0.05
 Brainsparring Without Brainsparring p
CPR (<13) CPR (>13)
n=63 n=126

Type of diabetes 0.018

- Type 1 3 (4.7%) 0 (0%)
- Type 2 15 (23.4%) 20 (15.9%)
- Gestational 46 (71.9 %) 106 (84.1%)
Type of treatment 0.388
- Diet 32 (50%) 71 (56.3)
- Diet + Metformyn 16 (25%) 34 (27%)
- Diet + Insulin 16 (25%) 21 (16.7%)
Emergency C-Section 39 (60.9%) 67 (53.2%) 0.425
Metabolic control (%) 13 (20.3%) 19 (15.1%) 0.414
Neonatal weight (grams) 3300 (2400-3920) 3275 (2560-4650) 0.417
Neonatal weight clasification 0.065
Adecuate for gestational age 54 (84.4%) 110 (87.3%)
(11-89 centil)
Big for gestational age 10(15.6%) 10 (7.9%)
(>90th centil)
Gestational age at delivery 39 (37-41.6) 39 (37-41) 0.942
Apgar at 5 minutes 9 (6-9) 9 (7-9) 0.01
Respiratory Morbidity 21 (33%) 1 (0.8%) 0.001
DRS 12 (18%) 0 0.001
Transient tachypnea of newborn 9 (14%) 1 (0.8%) 0.031
Suplementary O2 21 (32.8%) 4 (3.2%) 0.001
Cephalic helmet 2 (3.1%) 0 0.010
PPI 6 (9.4%) 0 0.001
UCIN 11 (17.2%) 0 0.001
£ Cualitative variables are compared wit X2* Cuantitative variables with non parametric distributions are compared using U Mann Whitney. ¥ Cuantitative
variables with parametric distribution are compared using Studen T Test. P value considered statistically significative is <0.05
Table 2. General characteristics divided by metabolic control

HbA1c >6.5% HbA1c <6.5% p

n=32 n=158

Age (years) 31 (18-46) 31 (18-42) 0.128

Pre-pregnancy weight (Kg) 72 (52-97) 70 (42-109) 0.871

Pre-pregnancy BMI * (Kg/m2) 28.6 +/- 4.83 28.9 +/- 5.32 0.741

Clasification

Normal 9 (28.1%) 37 (23.4%) 0.779

Overweight 11 (34.1%) 52 (32.9%)

Obese 12 (37.5%) 69(43.7%)

Actual weight * (Kg) 82.4 +/- 9.28 78.7 +/- 12.98 0.01

Weight gain (Kg) 11 (-4-22) 8 (-17-25) 0.021

Evolution time (Weeks) 15 (1-608) 14 (1-1078) 0.987

 HbA1c >6.5% HbA1c <6.5% p

Gestational age at ultrasound (Weeks) 38.1 (37-40) 38.3 (37-41) 0.293

Fetometry (Weeks) 37.1 (37-40) 38 (37-40) 0.164

Fetal weight (Kg) 3366 (2760-3800) 3433 (2035-3828) 0.213

Hba1c 6.9 (6.8-7) 5.6 (5-6) 0.001

Smoking 1 (3.1%) 3 (1.9%) 0.194

Alcoholism 0 (0%) 1 (0.6%) 0.828

Type of diabetes 0.447

- Type 1 0 (0%) 3 (1.9%)
- Type 2 4 (12.5%) 31 (19.6%)
- Gestational 28 (87.5%) 124 (78.5%)

Type of treatment 0.062

- Diet 18 (56.3%) 85 (53.5%)
- Diet + Metformyn 4 (12.5%) 46 (29.1%)
- Diet + Insulin 10 (31.3%) 27 (17.1%)
 HbA1c >6.5% HbA1c <6.5% p
Emergency C-Section 19 (59.4%) 87 (55.1%) 0.714
CPR Ratio Pth 35 (1-94) 30 (1-99) 0.51
Brain sparring effect (CPR <P13th) 13(40.6%) 51(32.3%)
Neonatal weight (grams) 3315 (2680-4650) 3300 (2400-3900) 0.197
Neonatal weight clasification 0.001
Adecuate for gestational age 22 (68.8%) 192(89.9%)
(11-89 centil)
Big for gestational age 10 (3.3%) 22(68.8%)
(>90th centil)
Gestational age at delivery 38 (37-40) 39 (37-41) 0.03
Apgar at 5 minutes 9 (7-9) 9 (7-9) 0.079
Respiratory Morbidity 16(49.5%) 18 (11.4%)
DRS 4(12.5%) 8(5.1%) 0.167
Respiratory taquipnea 12(37%) 10(6.3%) 0.170
Suplementary O2 10 (31.3%) 22(13.9%) 0.137
Cephalic helmet 1 (3.1%) 1 (0.6%) 0.248
PPI 2 (6.3%) 4(2.5%) 0.304
UCIN 4(12.5%) 7(4.4%) 0.119
Table 3. Neonatal outcomes of patients with CPR <13th

ICP < 13th Perinatal DRS Respirato Supplement

percentile Composit ry ary 02 need
e taquipne
Outcome a

OR 41.6 29 20 37.28
95% CI 5.47-316 3.72-23.2 2.57-1.68 12.25-113.41
 CPR in term pregnancies with diabetes
is a valuable and reliable screening
Conclusion test for Newborn´s Respiratory
Morbidity
Contact: moreno.uribe.nallely@gmail.com