Prematurity and Fetal Growth Restriction

Slide 1 · Prematurity and Fetal Growth Restriction

Definitions, etiologic mechanisms, pathologic correlates, and consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish gestational immaturity from impaired fetal growth.

Explain membrane rupture, infection, structural factors, and multiple gestation as causes of prematurity.

Classify maternal, fetal, and placental determinants of growth restriction.

Link causal mechanisms with neonatal hazards and growth patterns.

Clinicopathologic perspective

Two related clinical problems; Different causal questions

Slide 3 · Two distinct questions in perinatal pathology

Gestational age

Was delivery before 37 completed weeks?

Immaturity creates organ-system vulnerability.

A preterm infant can be appropriate in size for gestational age.

Fetal growth

Did the fetus achieve expected growth?

Growth reflects maternal supply, intrinsic fetal potential, and placental function.

An undergrown infant may be born at term.

Birthweight alone does not answer either question completely.

Slide 4 · Prematurity is defined by gestational age

<37

Completed weeks of gestation

An age-based category—not a weight-based diagnosis.

Prematurity contributes neonatal illness related to organ immaturity.

Always interpret neonatal weight in the context of gestational age.

Slide 5 · Birthweight is not a surrogate for gestational age

Birthweight measured

Gestational age established

Weight interpreted relative to age

Premature newborns may weigh less simply because fetal growth time was shortened.

At term, low birthweight may instead signal restricted fetal growth.

Slide 6 · Two dimensions: Gestation and attained size

Gestation

Appropriate size

Undergrown / SGA

Preterm

Shorter intrauterine maturation; weight may match age

Prematurity and undergrowth can coexist

Term

Completed gestational maturation with expected size

Low weight may reflect growth restriction

Schematic categories; No invented percentile threshold.

Slide 7 · Prematurity: A pathologic cascade

Early delivery

Immature neonatal organs

Higher vulnerability to disease

Timing of birth is the upstream event.

Clinical effects depend on maturity and superimposed complications.

Slide 8 · Clinical significance of preterm birth

Prematurity as the second most common cause of neonatal mortality after congenital anomalies.

The burden includes respiratory, intestinal, infectious, and intracranial complications.

Gestational age is central to risk assessment.

Clinicopathologic perspective

Source statement refers to the textbook context.

Slide 9 · U.S. Preterm birth in 2022

10.4%

Of infants born in the United States

CDC figures quoted by Robbins, 11th edition.

The source describes a 1% decrease compared with 2021.

These are historical 2022 figures—not a current prevalence estimate.

Slide 10 · Preterm birth rates differed between population groups (2022)

Percentage of live births classified as preterm

Historical 2022 figures. Group differences are descriptive and do not establish an individual causal mechanism.

Slide 11 · Four etiologic domains of prematurity

Preterm delivery

Premature membrane rupture

Intrauterine infection

Maternal reproductive-tract or placental structural problems

Multiple gestation

These factors can overlap rather than forming mutually exclusive diagnoses.

Slide 12 · PPROM: Failure of membranes before term

Membranes rupture

Verify prelabor onset and <37 weeks

Classify as PPROM

Preterm prelabor rupture of membranes (PPROM) exposes the amniotic cavity.

Timing distinguishes PPROM from rupture after 37 weeks.

Slide 13 · PPROM versus PROM

PPROM

Spontaneous membrane rupture before labor.

Occurs before 37 weeks of gestation.

Fetal immaturity is a major additional concern.

PROM after 37 weeks

Spontaneous rupture before labor.

Occurs after 37 weeks terminology.

Risks related to extreme prematurity are reduced.

Use gestational age and labor status together to classify rupture.

Slide 14 · PPROM: Contribution to preterm delivery

≈3%

Of all pregnancies complicated by PPROM

The book attributes as many as one-third of preterm deliveries to PPROM.

Frequency in all pregnancies is not the same denominator as fraction of preterm births.

Data are approximate figures as presented.

Slide 15 · Recognized clinical risk factors for PPROM

History during pregnancy

Maternal / social context

Previous preterm delivery

Maternal smoking

Current preterm labor

Low socioeconomic status

Vaginal bleeding in current pregnancy

Poor maternal nutrition

Risk factors are associations; None determines outcome alone.

Slide 16 · Antecedent obstetric history matters

Prior preterm delivery is a recognized risk factor for PPROM.

Preterm labor during the current pregnancy is also associated with rupture.

Current-pregnancy vaginal bleeding is another warning context.

Clinicopathologic perspective

Clinical history helps identify susceptibility, not a single mechanism.

Slide 17 · Maternal context and PPROM

Smoking, low socioeconomic status, and poor nutrition are associated with PPROM.

These exposures can coexist with obstetric risk factors.

The Robbins excerpt lists associations without assigning an individual causal effect size.

Clinicopathologic perspective

Avoid treating one association as sufficient proof of cause.

Slide 18 · PPROM prognosis is strongly dependent on timing

PPROM occurs

Assess fetal gestational age

Counsel about maturity-related prognosis

Second-trimester PPROM is described as having a very poor prognosis.

Risk changes as gestational maturity increases.

Slide 19 · PPROM also opens a route to intra-amniotic infection

Membrane barrier lost

Amniotic cavity exposed

Infection risk influences outcome

Prevention of infection in the exposed amniotic cavity contributes to outcome.

The source emphasizes infection prophylaxis alongside gestational maturity.

Slide 20 · Intrauterine infection and prematurity

≈25%

Of preterm births implicated

Intrauterine infection as a major cause of preterm labor.

This approximate contribution is not restricted to one pathogen.

Placental inflammatory morphology provides pathologic corroboration.

Slide 21 · Earlier preterm births: Infection becomes more prominent

Intra-amniotic infection

Inflammatory response

May precipitate early preterm labor

The association is qualitative; The source does not provide an age-stratified risk curve.

Do not interpret it as proof that all very early births are infectious.

Slide 22 · Placental inflammation has an anatomic location

PLACENTAL MEMBRANES

UMBILICAL CORD

Chorioamnionitis

Inflammation involving the placental membranes

Cord tissue

Funisitis

Inflammation involving the fetal umbilical cord

Simplified anatomic localization — schematic only, not a histologic specimen.

Slide 23 · Chorioamnionitis and funisitis

Chorioamnionitis

Inflammation of placental membranes.

Maternal–fetal interface is affected.

Histologic correlate of intrauterine infection.

Funisitis

Inflammation of the fetal umbilical cord.

Evidence that the fetal cord is involved.

May accompany infection-associated preterm labor.

Anatomic distinction is more useful than treating these terms as synonyms.

Slide 24 · How to read an inflammation-related placental report

Identify sampled tissue

Localize inflammatory infiltrate

Use correct pathologic term

Membranes → chorioamnionitis.

Umbilical cord → funisitis.

Slide 25 · Organisms implicated in intrauterine infection

Organism or infection

Textbook context

Ureaplasma urealyticum

Genital-tract organism implicated in preterm labor

Mycoplasma hominis

Implicated in intrauterine infection

Gardnerella vaginalis

Associated with bacterial vaginosis

Trichomonas

Protozoal infection listed among contributors

The list is illustrative, not a diagnostic ranking.

Slide 26 · Bacterial vaginosis: A polymicrobial context

Gardnerella vaginalis as a dominant organism found in bacterial vaginosis.

Bacterial vaginosis is described as polymicrobial.

Its placement in the source links genital-tract ecology with infection-associated prematurity.

Clinicopathologic perspective

Do not equate one isolated species with every case of bacterial vaginosis.

Slide 27 · Additional genital infections implicated in preterm labor

The source lists gonorrhea and Chlamydia among implicated infections.

Trichomonas is also listed in the relevant infectious spectrum.

The presence of a listed organism is not proof of causation in any individual delivery.

Clinicopathologic perspective

Infection is one cause among several.

Slide 28 · Global variation in infectious contributors

Malaria and HIV as important contributors in developing countries.

The epidemiologic context therefore differs across settings.

The source does not specify comparable country-level prevalence or relative risks.

Clinicopathologic perspective

Interpret population attribution in its geographic context.

Slide 29 · Proposed inflammation-to-contraction pathway

Bacterial components

Toll-like receptor signaling

Altered prostaglandin production

Uterine contractions

This chain as a proposed molecular mechanism.

TLRs recognize microbial ligands and may initiate signaling that changes uterine activity.

Slide 30 · Mechanistic uncertainty must remain visible

The TLR–prostaglandin model in the source is explicitly postulated.

Inflammation-associated preterm labor can be mechanistically plausible without being demonstrated in every case.

Histologic inflammation, organism detection, and clinical labor are distinct observations.

Clinicopathologic perspective

Hypothesis ≠ universal causal proof.

Slide 31 · Uterine distortion versus cervical support failure

Uterine distortion

Uterine fibroids can distort uterine architecture.

Anatomic abnormality is associated with prematurity.

Cervical structural weakness

Compromised cervical support is termed cervical incompetence.

Mechanical competence of pregnancy support is reduced.

Both belong to structural, rather than infectious, predisposition.

Slide 32 · Placental structural conditions linked with prematurity

Placenta previa is associated with an increased risk of preterm delivery.

Placental abruption (abruptio placentae) is another recognized association.

These complications are considered separately from infections and membrane rupture.

Clinicopathologic perspective

Some placental disorders also influence fetal growth.

Slide 33 · Multiple gestation and preterm delivery

Twin pregnancy

Greater risk of prematurity

Potential neonatal immaturity

Multiple gestation appears among Robbins’ major risk factors.

It may also contribute to growth restriction by placental mechanisms.

Slide 34 · A mechanistic map of prematurity

Preterm birth

Membrane rupture

Infection / inflammation

Uterine–cervical–placental anatomy

Multiple pregnancy

The unifying result is delivery before completion of gestation.

Slide 35 · Neonatal hazards of prematurity

Premature infant

Respiratory distress syndrome

Necrotizing enterocolitis

Sepsis

Germinal matrix / intraventricular hemorrhage

These complications are specifically named.

Slide 36 · Respiratory distress: An immature lung

Preterm delivery

Pulmonary immaturity

Neonatal respiratory distress syndrome

Robbins also calls this hyaline membrane disease.

The immediately following textbook section discusses surfactant deficiency in detail.

Slide 37 · Necrotizing enterocolitis as a neonatal hazard

Premature infant

Vulnerable intestinal system

Necrotizing enterocolitis

The condition is a recognized complication of prematurity.

Detailed NEC pathogenesis belongs to the adjacent Robbins topic.

Slide 38 · Sepsis in the premature newborn

Preterm birth

Newborn systemic infection hazard

Potential neonatal deterioration

Sepsis among the principal hazards of prematurity.

Intrauterine infection and neonatal sepsis should not be conflated as identical events.

Slide 39 · Germinal matrix and intraventricular bleeding

Premature infant

Vulnerable cerebral compartment

Germinal matrix / intraventricular hemorrhage

Bleeding in and around the germinal matrix is a named major hazard.

It exemplifies neurologic susceptibility associated with prematurity.

Slide 40 · Different hazards involve different organ systems

Complication

Dominant affected system

Teaching distinction

Respiratory distress syndrome

Lung

Respiratory immaturity

Necrotizing enterocolitis

Intestine

Necrotizing bowel disease

Sepsis

Systemic infection

Infectious complication

Germinal matrix hemorrhage

Central nervous system

Intracranial bleeding

Not a ranking of frequency or severity.

Slide 41 · Prematurity and restricted fetal growth can coexist

Prematurity

Age at birth is the defining variable.

Immaturity explains many neonatal vulnerabilities.

Size may be normal for gestational age.

Fetal growth restriction

Inadequate attainment of growth potential is the central issue.

Can occur in an infant delivered at term.

Causes are maternal, fetal, and placental.

Classification should consider both dimensions simultaneously.

Slide 42 · Low birthweight does not always imply prematurity

<2500 g

Includes a substantial term-born subgroup

As many as one-third of infants under 2500 g are born at term.

Such infants may be undergrown rather than gestationally immature.

Always assess age-appropriate size.

Slide 43 · FGR: The underlying problem is failed growth

An infant can be small because gestation ended early or because fetal growth was restricted.

, the undergrown term infant is considered in the small-for-gestational-age (SGA) context.

An underlying cause is sometimes unidentified despite evaluation.

Clinicopathologic perspective

Cause and phenotype should not be confused.

Slide 44 · Three major sources of fetal growth restriction

Fetal growth restriction

Maternal abnormalities

Intrinsic fetal abnormalities

Placental abnormalities

Grouping by compartment helps organize the diagnostic explanation. An unspecified cause remains possible.

Slide 45 · Maternal vascular disease: The common pathway

Maternal vascular disease

Reduced placental blood flow

Less effective fetal growth support

Maternal conditions that decrease placental blood flow are common among SGA infants.

This is an extrinsic limitation of fetal growth.

Slide 46 · Preeclampsia and chronic hypertension

Preeclampsia

Vascular disorder in pregnancy.

Named common maternal association with SGA.

Chronic hypertension

Pre-existing or chronic vascular burden.

Also implicated in impaired placental blood flow.

Both are linked through uteroplacental perfusion in the source.

Slide 47 · Maternal exposures: Preventable factors named by Robbins

Maternal opiate abuse is associated with fetal growth restriction.

Alcohol intake is another listed factor.

Heavy cigarette smoking is specifically emphasized.

Clinicopathologic perspective

Clinical counseling should distinguish association from proof in one fetus.

Slide 48 · Medications and maternal nutritional influences

Potential contributor

Textbook example

Chemotherapeutic agents

Classic teratogenic drug exposure

Phenytoin (Dilantin)

Commonly administered therapeutic agent listed

Maternal malnutrition

Reduced substrate availability for fetal growth

Prolonged hypoglycemia

Nutritional/metabolic influence specifically emphasized

The source provides examples, not an exhaustive medication-risk list.

Slide 49 · Maternal compromise: Interpret the pathway

Maternal abnormality or exposure

Affected fetal environment; Pathways vary

Potential fetal growth restriction

Decreased placental blood flow is the main pathway for maternal vascular disease.

Other listed maternal exposures may act through distinct mechanisms not specified in the excerpt.

Slide 50 · Intrinsic fetal factors: A different causal logic

Fetal genetic / developmental / infectious abnormality

Reduced intrinsic growth capacity

Symmetric growth restriction often results

Fetal causes may impair growth despite sufficient maternal nutrient supply.

Fetal pathology therefore differs conceptually from reduced uteroplacental delivery.

Slide 51 · Intrinsic fetal etiologies

Fetal abnormalities

Chromosomal disorders

Congenital structural anomalies

Congenital infections

These are the prominent fetal categories in the chapter.

Slide 52 · Chromosomal findings in selected FGR evaluations

Up to 17%

Of fetuses sampled for FGR

The source separately reports up to 66% in fetuses with ultrasonographically documented malformations.

These percentages describe selected samples, not universal population prevalence.

Sampling context is essential to interpretation.

Slide 53 · Chromosomal abnormalities in the selected FGR group

Abnormality

Proportion reported in source

Triploidy

7%

Trisomy 18

6%

Trisomy 21

1%

Trisomy 13

1%

Deletions and translocations

2%

These within the sampled FGR group; Do not generalize uncritically.

Slide 54 · Malformations change the cytogenetic context

FGR detected

Ultrasonographic malformation present

Chromosomal abnormalities more common in selected sample

Up to 66% in the malformation-enriched sampled group.

Interpretation depends on selection for testing rather than growth measurements alone.

Slide 55 · Congenital infections included in the TORCH framework

TORCH group

Toxoplasmosis

Other: E.g., syphilis

Rubella

Cytomegalovirus

Herpesvirus

Congenital infection should be considered in infants with growth restriction.

Slide 56 · Fetal pathology often yields proportionate small size

Intrinsic fetal insult

Multiple organ systems affected

Symmetric / proportionate FGR

Fetal etiologies with relatively uniform growth effects.

Pattern helps reason about cause but does not establish it on its own.

Slide 57 · Late gestation increases placental supply requirements

Third-trimester fetal growth

High demand on uteroplacental flow

Insufficiency can restrict growth

Placental function becomes especially important during rapid late fetal growth.

Mid-gestation placental development underpins later reserve.

Slide 58 · Placental growth in mid-trimester supports later growth

Mid-trimester placental development

Third-trimester perfusion capacity

Fetal oxygen and nutrient delivery

Insufficient development or disease may become functionally important later.

This explains why placental growth and fetal growth can become uncoupled.

Slide 59 · Umbilical–placental vascular abnormalities

Vascular/anatomic factor

How Robbins categorizes it

Single umbilical artery

Umbilical-placental vascular anomaly

Abnormal cord insertion

Umbilical-placental vascular anomaly

Placental thrombosis

Thrombotic placental abnormality

Placental infarction

Vascular injury to placenta

These entities may impair effective uteroplacental support.

Slide 60 · Additional placental lesions linked to FGR

Placental condition

Source grouping

Placental abruption

Placental abnormality

Placenta previa

Placental abnormality

Chronic villitis of unknown etiology

Inflammatory placental lesion

Placental infection

Infectious placental lesion

Multiple gestations

Placental context / demand

The chapter also allows unexplained small placenta and infant.

Slide 61 · An unexplained small placenta can accompany FGR

The placenta and infant may both be small with no discernible underlying cause.

Absence of a detectable lesion does not rule out clinically meaningful growth restriction.

Placental examination should be interpreted together with maternal and fetal findings.

Clinicopathologic perspective

Causal classification can remain unresolved.

Slide 62 · Placental insufficiency produces a supply constraint

Placental abnormality

Limited nutrients or oxygen

Down-regulation of later fetal growth

This as a physiologic adaptation to inadequate supply.

The pattern typically develops during the latter half of gestation.

Slide 63 · Relative brain sparing in placental FGR

Limited uteroplacental supply

Disproportionate somatic growth restriction

Relative sparing of brain growth

This is an asymmetric (disproportionate) growth pattern.

Brain sparing is relative, not proof that neurologic development is unharmed.

Slide 64 · Symmetric versus asymmetric restriction

Symmetric / proportionate

All organ systems similarly affected.

More typical of intrinsic fetal causes.

Examples: Chromosomal conditions, congenital infection.

Asymmetric / disproportionate

Relative brain sparing.

More typical of placental insufficiency.

Limited late fetal oxygen or nutrient supply.

Typical patterns are etiologic clues, not absolute diagnostic rules.

Slide 65 · How growth pattern informs the differential

Observed pattern

Etiologic emphasis

What remains unresolved

Proportionately small body and head

Intrinsic fetal abnormalities

Which genetic, developmental, or infectious cause?

Disproportionately reduced somatic growth

Placental nutrient/oxygen limitation

Which placental or maternal vascular lesion?

History and placental/fetal evaluation are still necessary.

Slide 66 · Consequences persist beyond delivery

Perinatal survival challenge

Childhood morbidity

Possible adult-life burden

Consequences beyond the neonatal period.

Outcome depends on underlying cause and, to a lesser degree, prematurity.

Slide 67 · Major disabilities associated with FGR

Potential morbidity

Cerebral dysfunction

Learning disability

Hearing impairment

Visual impairment

The chapter identifies these possible outcomes without assigning individual prognostic probabilities.

Slide 68 · Application: Membrane rupture before term

A pregnancy develops spontaneous membrane rupture before labor at 32 weeks. Which category is correct?

A. PPROM

B. PROM after term

C. FGR by definition

Interpretation: Rupture is prelabor and precedes 37 completed weeks.

Slide 69 · Application: Growth restriction with maternal hypertension

An undergrown infant is delivered at term. The mother has chronic hypertension. Which etiologic compartment deserves particular attention?

A. Intrinsic fetal abnormality exclusively

B. Maternal–placental perfusion

C. Prematurity as sole explanation

Interpretation: Chronic hypertension is a maternal vascular factor associated with reduced placental blood flow.

Slide 70 · Application: Proportionately small fetus

A fetus has uniformly reduced growth and a congenital infection is suspected. Which growth pattern is more consistent with the textbook discussion?

A. Asymmetric FGR with relative brain sparing

B. Prematurity is demonstrated by size

C. Symmetric FGR

Interpretation: Intrinsic fetal causes, including congenital infections, often affect all organ systems.

Slide 71 · Application: Placental vascular insufficiency

A fetus shows disproportionate somatic growth reduction. The placenta has vascular abnormalities. What mechanistic link is most consistent?

A. Uniform intrinsic growth-potential loss in every organ

B. Restricted oxygen and nutrient supply

C. An isolated demonstration of neonatal infection

Interpretation: Placental FGR commonly produces relative brain sparing under later gestational supply constraint.

Slide 72 · Integrated differential: Prematurity versus FGR

Prematurity

Diagnosed by gestational age <37 weeks.

Think PPROM, infection, structural factors, twins.

Anticipate lung, bowel, infection, and cerebral hemorrhage hazards.

Fetal growth restriction

Inadequate growth relative to gestation.

Think maternal, fetal, and placental factors.

Differentiate symmetric from asymmetric patterns.

A neonate may satisfy both clinical descriptions.

Slide 73 · Final synthesis: An etiologic approach

Assess gestational maturity independently from attained fetal size.

For prematurity, trace potential triggers: Membranes, inflammation, anatomy, and multiplicity.

For FGR, classify maternal supply, intrinsic fetal factors, and placental pathology.

Interpret neonatal and long-term consequences in light of both processes.

Clinicopathologic perspective

Mechanism → morphologic correlate → clinical vulnerability.

Slide 74 · Further reading and source context

Primary teaching source

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th ed. (2026). Elsevier.

Teaching emphasis: prematurity is defined by gestational age, whereas fetal growth restriction demands analysis of maternal, fetal, and placental determinants.