Introduction

Definition of placental insufficiency

Placental insufficiency is when placental vascular remodelling fails to occur, which is a process that increases the capacity of the maternal blood vessels to supply nutrients and oxygen to the developing foetus. This condition can lead to complications such as a failure in the formation of the placenta, intrauterine growth restriction, premature birth, or even foetal death. In general placental insufficiency is a progressive deterioration in the functioning of the placenta. Oxygen and nutrient transfer to the foetus via the placenta is decreased, resulting in decompensated hypoxia (reduced oxygen to the tissue) and acidosis, giving way to foetal hypoxemia (reduced oxygen to the blood).¹

Overview of stillbirth

Stillbirth has been recognised as a global public health issue reflecting the quality of care provided by healthcare professionals and institutions.² In the United States 1 child in every 175 children born is affected by stillbirth.³

Stillbirth is defined as the death of a foetus at 20 weeks gestation or later, which in most cases is due to placenta insufficiency.⁴ Here the baby is delivered with no signs of life. The global prevalence of stillbirth worldwide is at 13.9 stillbirths per 1000 total births. This prevalence varied across various regions with a prevalence of 22.8 in West and Central Africa compared to 2.9 stillbirths in Europe per 100 births.² Of note 98% of stillbirths occur in low- and middle-income countries. The underlying causes of stillbirth remain unknown in as many as half of recorded cases.

Placental insufficiency is associated with various obstetric disorders such as pre-eclampsia and intrauterine growth restriction, both of which predispose to preterm labour, a leading cause of perinatal morbidity (suffering from a disease/condition) and mortality (death) around the world.¹

Risk factors for placental insufficiency

Maternal factors

There are known maternal risk factors associated with pre-eclampsia or other maternal hypertensive disorders such as maternal cigarette use, maternal drug use (including cocaine or heroin), maternal alcohol consumption, being a first-time mother (primiparity), advanced maternal age, and a prior history of delivering an intrauterine growth restriction neonate.¹ 

Foetal factors

Advanced maternal age continues to be an independent risk factor for stillbirth, even when considering medical conditions that commonly affect older women. These conditions include multiple pregnancies (i.e. twin pregnancies), hypertension, diabetes, prior abortions, and placental abruption, each associated with increased stillbirth rates.⁵ 

Foetal growth restrictions have been reported as the major marker of placenta insufficiency. ⁶

Placental factors 

Placenta abruption occurs when the placenta separates from the womb before the baby is born (mothers may have bleeding or abdominal pain).

Various risk factors for stillbirth include low socio-economic status, ethnic minorities, advanced maternal age, pre-existing hypertension, diabetes mellitus, antepartum haemorrhage (APH), pre-eclampsia, foetal growth restriction, and reduced foetal movements.⁷ 

Clinical presentation and diagnosis of placental insufficiency

Signs and symptoms

Decreased foetal movement 

Reduced foetal movements have been increasingly found in women presenting with placenta dysfunction. Decreased foetal movements are considered an indicator of less-than-ideal conditions within the uterus. The foetus adapts to chronic hypoxia by conserving energy, and the resulting decrease in foetal movements is a survival mechanism to minimise oxygen consumption.⁸

Abnormal foetal growth patterns

Intrauterine growth restriction is defined as below-normal foetal growth considering the growth potential of a specific infant based on the foetus's race and gender. A normal neonate is defined as a baby whose birth weight falls between the 10^th and 90^th percentile for gestational age, gender, and race, with no signs of malnutrition.⁹ 

Foetal growth restriction secondary to placental insufficiency develops due to inadequate remodelling of the uterine spiral arteries as well as an obstruction to the umbilical cord. This causes a decrease in placenta function which causes foetal growth restriction.¹⁰

Diagnostic methods

Ultrasound findings 

Umbilical artery Doppler studies are important for checking if the placenta is working properly, and adding a middle cerebral artery (MCA) Doppler test helps provide more detailed information. The MCA Doppler looks at how well blood is flowing to the developing foetus, particularly to the brain, and can show if there are any problems with the small blood vessels in the brain. Normally, the MCA shows high resistance to blood flow during pregnancy, but if there is a placental disease, it can cause an increase in blood flow during certain phases of the heartbeat and a decrease in the pulsatility index, which helps doctors spot potential issues.¹ 

Non-stress test 

In the past two decades, the foetal non-stress test (NST) has been used primarily as a foetal surveillance method to assess foetal well-being.¹¹ Its major aim is to reduce the occurrence of stillbirth by monitoring foetal heart rate and movements.

Biophysical profile scoring

Biophysical profile is a painless procedure that combines ultrasound imaging with a non-stress test to assess the well-being of a foetus in the uterus. The biophysical profile (BPP) combines ultrasound observation of foetal behaviour (including foetal breathing movements, foetal movements, foetal tone, and amniotic fluid volume) with foetal heart rate monitoring. It is a sensitive test for determining the exhaustion of foetal reserve.⁸ 

Placental insufficiency as a cause of stillbirth

Mechanisms leading to stillbirth

Hypoxia occurs due to a reduction in oxygen supply in tissues. Intrauterine hypoxia refers to a deficiency of oxygen in maternal, placental, or foetal compartments as a result of compromised oxygen supply/demand balance.¹² Placental oxygen varies throughout pregnancy as oxygen delivery and metabolic demand increase with both placental and foetal development.

If hypoxia is prolonged in intrauterine life, it can be complicated with intrauterine growth restriction and increased perinatal mortality and morbidity. Some studies have demonstrated that mothers exposed to high altitudes for longer periods are at risk of developing hypoxia.¹³ 

Hypoxia in a foetus can be caused by two main things: pre-placental hypoxia (such as from being at high altitudes) or uteroplacental hypoxia, where the mother’s oxygen levels are fine but the blood flow to the placenta and foetus is restricted. The second type is the main cause of fetal growth restriction.¹²

When the foetus doesn't get enough oxygen, it tries to adapt by redirecting blood flow to vital organs, like the brain, in an effort to survive. But if the oxygen shortage becomes too severe and the foetus can no longer cope, it can lead to severe complications, like foetal death.¹²

Although the foetus has a strong ability to adapt to low oxygen by using protective mechanisms to grow, if the placenta’s function keeps worsening, the foetus may not be able to keep up. This leads to growth restriction due to reduced oxygen and nutrient supply.

Doctors can monitor for signs of hypoxia or acidosis (which indicates oxygen problems) using foetal heart rate monitoring during pregnancy.

Management and prevention of placental insufficiency

Monitoring strategies

Ultrasounds to assess foetal growth

Ultrasounds are used to identify high-risk pregnancies and provide more targeted and appropriate treatment while monitoring foetal well-being in both low- and high-risk pregnancies.

A study among pregnant women in Egypt revealed antenatal ultrasonic evaluation predicted 89.7% of cases with intrauterine growth retardation compared to only  34.7% of cases identified with fundal palpation (a form of physical examination).¹⁴ 

The identification and management of growth-restricted foetus remains a significant opportunity for stillbirth prevention.⁵ Regular prenatal screening associated with Doppler ultrasound should be done throughout the gestation period.

Doppler ultrasound is used to examine placental blood flow velocity, which evaluates foetal and placenta circulations and is recommended in high-risk pregnancies.¹⁵ Foetal death is mostly suspected if the foetal heart cannot be heard.⁷

The gold standard for imaging in pregnancy is real-time ultrasound, which provides an overview of the four chambers of the fetal heart. Features to watch out for in the ultrasound are the absence of foetal cardiac activity, overlapping skull bones (Spalding’s sign) and hydrops. The diagnosis of foetal death requires confirmation by two competent ultrasound practitioners.⁷ 

Interventions to improve outcomes

Maternal lifestyle modifications

In the absence of previous obstetric history, the patient's risk for stillbirth is associated with her underlying health conditions and lifestyle choices. Therefore certain modifications should be undertaken and additional measures should be put in place.

• Screening for hypertension and diabetes is essential to prevent poor pregnancy outcomes.
• Each patient should undergo risk assessment for their case
• Smokers should cease smoking during pregnancy
• Prevalence and surveillance of pregnancies at risk of foetal growth restrictions
• Health professionals should execute effective foetal monitoring during labour⁷
• Nutrient supplementation with balanced calorie intake rather than specific protein supplementation is encouraged⁸

Medical interventions 

Extensive research has been conducted on the use of low-dose aspirin for the prevention and treatment of pre-eclampsia and intrauterine growth restriction.¹⁶ 

In cases where foetal growth restriction is induced by pre-eclampsia, antihypertensive therapy in association with magnesium sulphate should be used to control blood pressure to prevent pulmonary oedema and cerebral haemorrhage. The treatment aims to normalise systolic blood pressure. This prolongs the pregnancy, which is of benefit to the foetus.

Timing and mode of delivery decisions

Pregnant mothers should raise awareness of reduced fetal movements (RFM). The rationale for foetal movement counting is that decreased foetal movements signal decreased oxygenation, which often precedes foetal death.¹⁶ A decrease in these counts indicates possible foetal compromise which needs immediate medical attention for further diagnosis and management.

At full-term, a healthy foetus can handle the lack of oxygen during labour. However, a foetus with placental insufficiency, which causes growth problems, has much less ability to cope because its energy stores are depleted. In most cases of placental insufficiency, a Doppler test on the umbilical cord shows abnormal blood flow and a cesarean section is needed. Vaginal delivery can only be considered with very careful monitoring. Foetal heart rate should also be monitored during labour and if compromised, continue with a caesarian section delivery.⁸ 

Prognosis and outcomes

In cases where the foetus suffers from intrauterine growth restriction due to placenta insufficiency and survives the pregnancy, the foetus is at high risk of developing cognitive deficits in childhood, including cerebral palsy and seizure disorders.¹

Evidence suggests that infants who suffer from intrauterine growth restriction are also predisposed to chronic illnesses in adulthood, such as coronary artery disease, hypertension, and diabetes. Neurodevelopmental disorders will mostly occur if the neonate suffers from uteroplacental hypoxia (where the placenta does not receive enough oxygen).¹²

Understanding the underlying mechanisms associated with the placental dysfunction or placenta insufficiency associated with intrauterine hypoxia, and foetal growth restriction is essential in reducing the occurrence of stillbirth. Each pregnancy is different and needs to be assessed to determine if it's a high-risk pregnancy or not. Mothers should be ready to make adjustments to their lifestyle to improve the probability of delivering a healthy foetus.

Summary

• Placental insufficiency is when the placenta can't provide enough oxygen and nutrients to the fetus, leading to complications like foetal growth restriction, premature birth, and stillbirth
• This is due to poor blood flow in the placenta
• Risk factors:
  • Maternal smoking, drug use, advanced age
  • Fetal growth restrictions
  • Pre-existing health conditions (e.g., hypertension, diabetes)
• Ultrasound and Doppler studies are used to monitor fetal growth and blood flow
• It is treated using lifestyle changes for the mother (e.g., stopping smoking), medications like blood pressure control, and early delivery, often via cesarean section, if necessary
• There is an increased risk of developmental and health issues later in life (e.g., cognitive delays, heart disease)