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Documenti di Cultura
Johanes C.Mose
Cerebral palsy
Minor neurological
dysfunction
Poor social competence
Figure 7. Increased risk for various physical and neurodevelopmental problems in intrauterine growth restricted neonates when they reach their
childhood and adulthood. Figure Copyright Deepak Sharma.
Tybe 2 diabetes
Hypertension/obesity
Metabolic programming/Epigenetic
modification in antenatal period
Ischemic Heart
disease/Stroke
Postnatal abnormal nutrition
PCOD/premature
pubarche
Renal/Hepatic
Adult male and female disease
Figure 8. Figure showing various adult disease the IUGR infant is prone to develop in his adulthood as per “Developmental origin of health and diseases
(DoHaD)”. IUGR infants undergoes epigenetic modification in-utero and postnatally have abnormal nutrition and growth leading to various disease of
adulthood in these infants. Figure Copyright Deepak Sharma.
Placental factors
Less cell in fetal Abnormal vascular
Genetic factors pancreas development
Postnatal excessive
nutrition
Abnormal postnatal
growth (obesity) Type 2 diabetes
Adult with decreased mellitus
cell of pancreas
Figure 9. Barker Hypothesis (Thrifty phenotype) explaining the Fetal Origin of Adult Disease (FOAD) or “Developmental origin of health and diseases
(DoHaD)” in IUGR infants. Figure Copyright Deepak Sharma.
Table 7. Various “developmental origin of health and diseases
(DoHaD)” seen in IUGR neonates in adulthood.
v Hypertension
v Ischemic Heart disease/ Stroke
v Type 2 diabetes mellitus
v Kidney disease
v Liver disease
v Hypercholesterolemia
v Metabolic syndrome X
v Obesity
v Lung abnormalities- reactive airways disease
v Cancer- breast, ovarian, colon, lung, blood
v Schizophrenia/ Parkinsonism
v Alzheimer disease
v Polycystic ovarian syndrome, premature pubarche
v Shortened life span
v Depression, anxiety, bipolar disorder
v Immune dysfunction
v Osteoporosis
v Social problems
v Poor cognitive performance
Figure 1. IUGR can be the result of maternal, fetal, placental, genetic cause or can be combination of either of the combination. (Copyright images
Deepak Sharma).
e 2. Maternal causes for
Table 2. Maternal intrauterine
causes growthgrowth
for intrauterine restriction.
restriction. TableTable
3. Placental causes
3. Placental for for
causes intrauterine growth
intrauterine growthrestriction.
restriction.
v Maternal age (less than 16 years and more than 35 years) v Placental weight (weight less than 350 gram)
Maternal age (less than 16 years and more than 35 years)
v High altitude and maternal hypoxia
v Placental weight (weight less than 350 gram)
v Abnormal uteroplacental vasculature
igh altitude
v Low and maternal hypoxia
socioeconomic status and developing country v Abnormal uteroplacental
v Placental vasculature
dysfunction (PIH, pre-eclampsia)
v Ethnicity or race
ow socioeconomic status and developing country v v Thrombophilia-related
Placental dysfunction (PIH,uteroplacental
pre-eclampsia) pathology
v Maternal substance abuse (smoking both active and passive, v Confined placental mosaicism (CPM)
thnicity alcohol,
or race illicit drugs like marijuana or cocaine) v Thrombophilia-related
v Avascular villi uteroplacental pathology
v Maternal
Maternal substancemedication
abuse (smoking
(warfarin,both activeanticonvulsants,
steroids, and passive, v v Decidual
Confined placental
or spiralmosaicism (CPM)
artery arteritis
antineoplastic, anti-metabolite, and folic acid antagonists) v Multiple infarctions
lcohol,v illicit drugstolike
Moderate marijuana
heavy physicalorwork
cocaine) v Avascular
v Partialvilli
molar pregnancy
Maternal medication
v Maternal (warfarin, steroids,
pre-pregnancy height andanticonvulsants,
weight (BMI less than 20, v Decidual or spiral
v Syncytial knotsartery arteritis
weight less than 45 kg and more than 75 kg) v Chronic inflammatory lesions
ntineoplastic,
v Parity anti-metabolite,
(none and more than and 5folic acid antagonists)
birth) v Multiple infarctions
v Single umbilical artery
Moderate to heavy
v Inter physical
pregnancy work(less than 6 months or 120 months or
interval v Partial molarplacenta
v Abruptio pregnancy
Maternal more)
pre-pregnancy height and weight (BMI less than 20, v v Velamentous
Syncytial knots cord
v Previous delivery of a SGA newborn v Placental hemangioma
eightv less than 45reproductive
Assisted kg and more than 75 kg)(ART)
technologies v Chronic inflammatory
v Placental infectionslesions
(Placental malaria)
v Pregnancy
arity (none and morepoorthan 5 birth)
medical care v v Infectious
Single umbilicalvillitis
artery
v Pregnancy severe maternal starvation. v Multiple gestation
nter pregnancy
v Pregnancy interval
poor (less
weightthan
gain6 months or 120 months or v Abruptio placenta
v Chronic villitis of unknown etiology (CVUE)
more) v Maternal Bronchial asthma, cyanotic congenital heart diseases v Velamentous cord
v Reduced expression of enzymes for redox regulation (thiore-
v Hematologic and immunologic disorders (Acquired doxin, glutaredoxin)
revious delivery of a SGA
thrombophilias, suchnewborn
as anti-cardiolipin antibodies and lupus v Placental hemangioma
ssisted anticoagulant)
reproductive technologies (ART) v Placental infections (Placental malaria)
v Maternal medical disorders (hypertensive disorders (gesta-
regnancy poor medical care
tional and non-gestational), diabetes associated with vascul-
v Infectious villitis
regnancyopathy,severechronic
maternal
renalstarvation.
disease, systemic lupus erythematosus, v Thegestation
Multiple role of Insulin-like growth factor-II (IGF-II),
regnancyantiphospholipid
poor weight gain syndrome, sickle cell disease v Insulin-like
Chronic villitis ofgrowth
unknown factor binding
etiology (CVUE)protein-2 (IGFBP-2),
v Pathological conditions in pregnancy like preeclampsia and
Maternal diabetes
Bronchialassociated
asthma, cyanotic congenital heart diseases
with vasculopathy v Insulin-like
Reduced growthoffactor
expression binding
enzymes protein-3
for redox (IGFBP-3),
regulation (thiore- and
ematologic
v Maternal and immunologic disordersinfestations
infection and parasite (Acquired(TORCH, malaria, vasoactive
doxin, intestinal polypeptide (VIP) in IUGR have been
glutaredoxin)
tuberculosis, urinary tract infections and bacterial vaginosis) proved. In the various preclinical trials, mutation in IGF-II
hrombophilias, such as anti-cardiolipin antibodies and lupus
Curr Obstet Gynecol Rep (2013) 2:102–111 107
trimester serum screening can be associated with IUGR [68•]. Another simple tool commonly used in office includes
Curr Obstet Gynecol Rep (2013) 2:102–111 107
Absent - Preeclampsia
ABRUPTION
PLACENTAE
GESTATIONAL
12 16 < 34 > 34
AGE (WEEKS)
LATE
SPONTANEOUS
ABORTION
DEFECTIVE
PLACENTATION
IUGR
THE “GREAT OBSTETRICAL SYNDROMES” ARE ASSOCIATED WITH DISORDERS
OF DEEP PLACENTATION
Ivo Brosens, MD, Robert Pijnenborg, PhD, Lisbeth Vercruysse, MSc, and
Roberto Romero, MD. Am J Obstet Gynecol. 2011 Mar; 204(3): 193–201.
of both symmetrical and asymmetrical IUGR at birth. This deficiency, IUGR results because of reduced uptake and uti-
type of IUGR results when early IUGR is affected further by lization of nutrients.12 In preclinical trials, it has been shown
placental causes in late pregnancy.6 that pancreatic agenesis of the fetus leads to fetal hyperglyce-
mia and this results in secondary decrease in the maternal–
Causes of IUGR fetal glucose concentration gradient; thus, there is a decrease
IUGR is the common end result of maternal, placental, in glucose transport to the fetus, leading to IUGR.13
fetal, or genetic factors, and IUGR can also result due to a Insulin-like growth factor-I (IGF-I) is positively regu-
combination of any of these factors (Fig. 1). Various maternal lated by glucose supply in the fetus. It has mitogenic properties
Note: Adapted from Sharma D, Farahbakhsh N, Shastri S, Sharma P. Intrauterine growth restriction–part 2. J Matern Fetal Neonatal Med. 2016 Mar 15:1–12.
[Epub ahead of print] PubMed PMID: 26979578 with permission.
CLINICAL ASPECT
• SCREENING & PREDICTION
• DIAGNOSIS
• FETAL SURVEILLANCE
• MANAGEMENT
RISK FACTORS
CLINICAL ASPECT
PREDICTION &
SCREENING ,
DIAGNOSIS
SFH
MEASUREMENT
SIGNS AND SYMPTOMS
DOPLER USG
GESTATIONAL
12 16 < 34 > 34
AGE (WEEKS)
PREVENTION &
MANAGEMENT
TREATMENT
1. CLINICAL SCREENING & EARLY
DETECTION
• Identifying Risk Factors
• Measurement of Fundal
Height
• Uterine artery Doppler
CLINICAL SCREENING
A Risk factors
Ø Low socioeconomic environment
Ø Family history of IUGR
Ø Previous delivery of IUGR infant
Ø Cigarette smoking
Ø Low pre-pregnancy weight
Ø Poor maternal weight gain
Ø Medical complication of pregnancy
Ø Decreased fundal height
RISK FACTORS FOR IUGR
• DETECTABLE BEFORE CONCEPTION
- Previous fetal growth restriction
- History of chronic illness
- History of antiphospholipid syndrome
- Low maternal body mass index
- Substance abuse (including alcohol)
- Maternal hypoxia
CONSTITUTIONALLY
SMALL
IUGR
C ULTRASOUND SCREENING
MONITORING/ SURVEILLANCE
CARDIOTOCOGRAPHY
UMBILICAL ARTERY DOPPLER
NORMAL REDUCED
ABSENT REVERSED
Umbilical Artery (UA) Doppler
Middle Cerebral Artery (MCA) & Thoracic
Aorta Doppler
DUCTUS VENOSUS
Ductus Venosus
• Normal
• Reversed
EDF
UMBILICAL VENOUS PULSATIONS
MONITORING
&
EVALUATION
(Arduini D,et al,
1992)
(Baschat AA,
2004)
(Baschat AA, 2005)
Mari G, Hanif F, Drennan K, Kruger M. Staging of intra-uterine growth restriction fetuses. J
Ultrasound Med 2007;26:1469-1477
MANAGEMENT/INTERVENTION
Booking assessment
(first trimester)
Risk assessment must always be individualised (taking into account previous medical and obstetric history and current pregnancy history). Disease progression or
institution of medical therapies may increase an individual’s risk.
Fetal biometry
Single AC or EFW <10th customised centile
serial measurements indicative of FGR
UA Doppler
Refer
for
fetal medicine
specialist
opinion
Normal PI or RI >2 SDs, EDV present AREDV
Bujold, Emmanuel MD, MSc; Roberge, Stéphanie MSc; Lacasse, Yves MD, MSc; Bureau, Marc MD; Audibert, François MD,
MSc; Marcoux, Sylvie MD, PhD; Forest, Jean-Claude MD, PhD; Giguère, Yves MD, PhD
Abstract
OBJECTIVE: To estimate the effect of low-dose aspirin started in early pregnancy on the incidence of preeclampsia and
intrauterine growth restriction (IUGR).
DATA SOURCES: A systematic review and meta-analysis were performed through electronic database searches (PubMed,
Cochrane, Embase).
METHODS OF STUDY SELECTION: Randomized controlled trials of pregnant women at risk of preeclampsia who were
assigned to receive aspirin or placebo (or no treatment) were reviewed. Secondary outcomes included IUGR, severe
preeclampsia and preterm birth. The effect of aspirin was analyzed as a function of gestational age at initiation of the
intervention (16 weeks of gestation or less, 16 weeks of gestation or more).
TABULATION, INTEGRATION, AND RESULTS: Thirty-four randomized controlled trials met the inclusion criteria, including
27 studies (11,348 women) with follow-up for the outcome of preeclampsia. Low-dose aspirin started at 16 weeks or
earlier was associated with a significant reduction in preeclampsia (relative risk [RR] 0.47, 95% confidence interval [CI]
0.34–0.65, prevalence in 9.3% treated compared with 21.3% control) and IUGR (RR 0.44, 95% CI 0.30–0.65, 7% treated
compared with 16.3% control), whereas aspirin started after 16 weeks was not (preeclampsia: RR 0.81, 95% CI 0.63–1.03,
prevalence in 7.3% treated compared with 8.1% control; IUGR: RR 0.98, 95% CI 0.87–1.10, 10.3% treated compared with
10.5% control). Low-dose aspirin started at 16 weeks or earlier also was associated with a reduction in severe
preeclampsia (RR 0.09, 95% CI 0.02–0.37, 0.7% treated compared with 15.0% control), gestational hypertension (RR 0.62,
95% CI 0.45–0.84, 16.7% treated compared with 29.7% control), and preterm birth (RR 0.22, 95% CI 0.10–0.49, 3.5%
treated compared with 16.9% control). Of note, all studies for which aspirin had been started at 16 weeks or earlier
included women identified to be at moderate or high risk for preeclampsia.
CONCLUSION: Low-dose aspirin initiated in early pregnancy is an efficient method of reducing the incidence of
preeclampsia and IUGR.
ASPIRIN TREATMENT WORKS, IF STARTED EARLY
Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu
Original article
a r t i c l e i n f o s u m m a r y
Article history: Background & aims: Vitamin D deficiency during pregnancy is a worldwide epidemic. This study aimed
Received 13 November 2017 to identify whether vitamin D deficiency in early pregnancy is associated with placental inflammation in
Accepted 23 June 2018 high-risk pregnancy.
Methods: This study comprised 23,396 women who provided serum samples in the first trimester for
Keywords: vitamin D analysis from January 2015 to December 2016. Among them, 2648 women with high-risk
Vitamin D
pregnancy underwent placental pathologic examination. Women were divided into placental inflam-
Placental inflammation
mation positive (PIP) and placental inflammation negative (PIN) groups based on placental pathology.
High-risk pregnancy
Neonatal outcome
Multivariate logistic regression was used to evaluate the relationship between vitamin D levels and
placental inflammation.
Results: We found that severe vitamin D deficiency in early pregnancy was associated with placental
inflammation. Maternal vitamin D levels were significantly lower in the PIP group than those in the PIN
group (P ¼ 0.025). Compared with the highest quartile of vitamin D levels, risk for placental inflam-
mation was significantly higher in women with extremely low vitamin D levels (<5th percentile;
P ¼ 0.012). The effect estimate was slightly decreased but still significant (P ¼ 0.027) after adjusting for
maternal age, gestational age at birth, birth weight, infant sex, and sample collection season. In addition,
compared with the PIN group, the incidences of adverse neonatal outcomes, including sepsis (0.5% vs
2.4%) and fetal intrauterine infection (5.7% vs 15.6%), were significantly higher in the PIP group than that
in the PIN group (P < 0.001).
Conclusions: Severe vitamin D deficiency in the first trimester is a risk factor for placental inflammation
in high-risk pregnancy.
© 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Article Navigation
The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 5, 1 May 2015, Pages
1912–1919, https://doi.org/10.1210/jc.2014-4407
Published: 01 May 2015 Article history
Obstet Gynecol. Author manuscript; available in PMC 2015 Jan 1. PMCID: PMC3914014
Published in final edited form as: NIHMSID: NIHMS542703
Obstet Gynecol. 2014 Jan; 123(1): 40–48. PMID: 24463662
doi: 10.1097/AOG.0000000000000049
Copyright notice
The publisher's final edited version of this article is available at Obstet Gynecol
See other articles in PMC that cite the published article.
THE GREAT OBSTETRICAL SYNDROMES
PPROM
PRETERM
PRE
ECLAMPSIA LABOR
ABRUPTION
PLACENTAE
GESTATIONAL
12 16 < 34 > 34
AGE (WEEKS)
LATE
SPONTANEOUS
ABORTION
DEFECTIVE
PLACENTATION
IUGR
RISK FACTORS
PREDICTION &
SCREENING ,
DIAGNOSIS
SFH
MEASUREMENT
SIGNS AND SYMPTOMS
DOPLER USG
GESTATIONAL
12 16 < 34 > 34
AGE (WEEKS)
CORTICOSTEROIDS
MgSO4
PREVENTION &
CALCIUM
TREATMENT
ASPIRIN
VITAMIN D
TOP (DELIVERY)
TOP (DELIVERY)
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium : 1,5-2 gram/day
CALCIUM
ASPIRIN
VITAMIN D
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
CALCIUM
2. ASPIRIN 150 mg/day started at 12- 16
weeks of pregnancy
ASPIRIN
VITAMIN D
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
VITAMIN D
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
CALCIUM
2. ASPIRIN 150 mg/day starting at 12- 16 weeks of
pregnancy
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
CALCIUM
2. ASPIRIN 150 mg/day starting at 12- 16 weeks of
pregnancy
FOLATE
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
CALCIUM
2. ASPIRIN 150 mg/day starting at 12- 16 weeks of
pregnancy
LMWH
METFORMIN
PRAVASTATIN
1. Calcium 1,5-2 gram/day
CALCIUM
2. ASPIRIN 150 mg/day starting at 12- 16 weeks of
pregnancy
ASPIRIN 3. Vitamin D : 4000 IU/day starting at 12- 16
weeks of pregnancy
METFORMIN
PRAVASTATIN
MANAGEMENT OF IUGR : SUMMARY
1. Elimination of contributing factors, ie:
Hypertension, infections, alcohol, smoking,
drug abuse, etc.
2. Bed rest, optimally on left side & O2 therapy
3. Vitamin D & Dietary supplementation
4. Calcium 1-2 gm/day, Aspirin 150 mg/day,
Pravastatin, Metformin, Folic Acid, LMWH, etc
5. Corticosteroids at < 36 weeks
6. MgSO4 for fetal brain protection (< 32 weeks)
7. Fetal functional assessment (Doppler, CTG, BPP)
8. Termination Of Pregnancy (TOP) when :
- Doppler : - A/RED umbilical artery
- A/RAV (absent or reversed
arterial contraction) of ductus
venosus.
- UV pulsation
- Olygohydramnion
- Abnormal CTG
- Abnormal BPP
- pH < 7,2
(Evidence level I a, Recommendation A)
9. Mode of delivery :
Caesarean Section : - Premature
- Fetal distress (point 9)
Induction for vaginal delivery :
- Term pregnancy
- Intrapartum continuous monitoring (Ia, III, C)
- Deliver in a unit with optimal neonatal expertise
and facilities are available ( Evidence IV, C)