Intrauterine Growth Restriction (IUGR)

Intrauterine Growth Restriction (IUGR) is a common pregnancy complication that occurs when a fetus is not growing at the normal, expected rate during pregnancy. IUGR increases the fetus' risk of morbidity and birth injuries. The formal definition of IUGR is a fetal weight rank lower than the 10th percentile for the gestational age. Fetal weight below this mark is called small for gestational age (SGA). However, not all babies who are small for gestational age suffered from IUGR during pregnancy. There are 2 recognized types of IUGR:

• Symmetric / Primary IUGR: primary or symmetric IUGR occurs when all parts of the baby including the internal organs are proportionally small in size. Around 25% of all IUGR cases are classified as symmetric.
• Asymmetric / Secondary IUGR: with secondary or asymmetric IUGR the baby's head and brain are normal sized but the abdominal area and rest of the body are abnormally small.

IUGR is caused by an inadequate supply of nutrients and oxygen to the fetus during gestation. Nutrients and oxygen fuel the growth and development of the fetus during pregnancy. They are basically like food for the fetus. When the fetus does not get enough food it doesn't grow at a normal rate. The real question is what is causing the nutrient insufficiency. Transmission of maternal oxygen and nutrients to the fetus during pregnancy is the normally the function of the placenta and umbilical cord. Most causes of inadequate nutrients and IUGR involve the placenta. Placental insufficiency is the leading cause of IUGR:

• Placental Insufficiency: placental insufficiency (also called placental dysfunction) is a serious pregnancy complication where the placenta develops abnormally or becomes damaged. This abnormal development is usually the result of the placenta not getting adequate blood flow from the mother when pregnancy begins. Many IUGR can be seen in cases there is placental malperfusion that prevents sufficient nutrients from being delivered from the mother to the baby.

Other potential causes of IUGR include the following:

• Substance Use: smoking cigarettes, using alcohol, or drug use during pregnancy can disrupt nutrient and oxygen supply and trigger IUGR.
• Maternal Infection: a number of maternal infections have been shown to affect the delivery of nutrients to the baby during pregnancy.
• Maternal Hypertension: maternal high blood pressure or other cardiovascular disorders can restrict blood circulation to the placenta and restrict nutrient supply to the baby.
• Birth Defects: genetic birth defects and chromosomal abnormalities can also interfere with nutrient and oxygen delivery to the baby during pregnancy.

There are a number of known risk factors for IUGR, many of which tend to overlap with the underlying causes listed above. One of the strongest risk factors for IUGR is multiple pregnancy (i.e., twins, triplets, etc.). A pregnancy with twins or triplets is much more likely to involve IUGR than a singleton pregnancy. Women who are chronically underweight or with a history of eating disorders are also at increased risk of IUGR. Finally, certain maternal medical conditions including diabetes, anemia and cardiovascular disorders can make IUGR during pregnancy more likely.

The first critical step in diagnosing IUGR is dating the start of the pregnancy with a high degree of accuracy. The timely diagnosis of IUGR is essential to ensuring a positive outcome. Many studies have shown that fetal mortality and morbidity increase when IUGR is not properly or timely diagnosed. When properly diagnosed, the standard of care requires intense antenatal surveillance with regular non-stress tests and biophysical profiles.

Dating the pregnancy (i.e., the day shortly after conception when the embryo attached to the uterus) is crucial because a diagnosis of IUGR is wholly dependent on the gestational age of the baby and gestational age is based on dating the pregnancy. During the first 2 months of pregnancy, gestational age is based on the date of the mother's last period. Sometime after week 9-10 the first ultrasound test is done and doctors use this to further refine the date of the pregnancy. Dating the pregnancy allows doctors to calculate the baby's gestational age. Once the gestational age is fixed the growth of the baby can be tracked and analyzed based on charts of normal growth rates. Calculating the size and weight of fetus can be difficult. Doctor estimate size based on uterine fundal height measurements and ultrasound imaging.

Once IUGR is diagnosed, the appropriate course of treatment or management will usually depend largely on how far along the pregnancy is and the apparent health of the baby. If the pregnancy is in week 34 or more, most doctors will suggest early delivery of the baby either by inducing labor or scheduling a C-section. Prior to week 34 early delivery of the baby is generally not recommended unless the baby's health is at risk. When IUGR is diagnosed this early the appropriate response is to identify and treat the underlying cause of the IUGR (e.g., treating a maternal infection, improving maternal nutrition). Doctors will try to prolong the pregnancy to allow the baby to continue developing. Very close monitoring will usually be required with weekly or twice weekly appointments for the duration of the pregnancy.

IUGR can result in a number of health problems for the baby and significantly increase the risk of further complications and potential birth injuries. IUGR makes premature delivery much more likely. Few pregnancies with IUGR go full term. Anytime a baby is born prematurely they are at risk of numerous birth injuries from oxygen deprivation. The most significant potential risks of IUGR are:

• Hypoxia from oxygen deprivation during childbirth
• Meconium aspiration
• Low blood sugar

The standards of care for obstetricians requires the doctor to screen for IUGR. You do not need to present with risk factors. Every pregnant woman should be screened. This assessment can be based upon measurements made by looking at the mother's weight gain or lack thereof because IUGR diagnosis is predicated on the weights of the newborn and size of the placenta. Doctors also look at serial ultrasonic studies and fundal height measurements that may be inconsistent with normal fetal development.

If there is a concern about IUGR based upon fetal weight or fetal measurements, the standard of care requires that the woman be placed at bed rest and additional testing be done to ascertain a maternal or fetal cause for the IUGR. The mother and child must be closely monitored. This puts the physician is in a position to determine the best time to induce labor or take the baby by Caesarian delivery. This monitoring requires serial non-stress testing, serial ultrasonic studies, BPP assessments and calculation of an accurate gestational age for the fetus. This allows the doctor to determine the various levels of maturity.

Intrauterine Growth Restriction - Studies & Research

Armengaud, J. B., et al. "Intrauterine growth restriction: Clinical consequences on health and disease at adulthood." Reproductive Toxicology. 99. (2021): 168-176. (This review summarized information on IUGR’s long-term effects.  It reported that this condition affects all organs. The review also reported that IUGR was related to liver and heart diseases, metabolic syndrome, and neuroinflammation. It concluded that increased knowledge of these conditions’ mechanisms could help screen and prevent long-term complications.)  

 Bahado-Singh, R.O., et al. "Artificial intelligence and the analysis of multi-platform metabolomics data for the detection of intrauterine growth restriction." PloS One. 14.4. (2019): e0214121. (This study looked at whether artificial intelligence could detect IUGR. The researchers used a set of metabolites to develop an algorithm that would detect the condition’s signs. They found that their metabolite set detected IUGR with 78 to 82 percent accuracy. The researchers concluded that AI could “accurately detect IUGR in newborn cord blood serum.”) 

 Barenys, M., et al. "Rabbit neurospheres as a novel in vitro tool for studying neurodevelopmental effects induced by intrauterine growth restriction." Stem Cells Translational Medicine. 10.2. (2021): 209-221. (This study looked at the development of 3D rabbit neurospheres that model IUGR’s neurodevelopmental effects. This was done to test for toxicity and pharmaceutical drugs’ efficacy. The researchers showed that neurospheres from IUGR brains showed oligodendrocyte differentiation impairments. They also showed that they could use thyroid hormones via in vitro exposure to treat these impairments.)  

 Menendez-Castro, C., Rascher, W., & Hartner, A. "Intrauterine growth restriction-impact on cardiovascular diseases later in life." Molecular and Cellular Pediatrics. 5.1. (2018): 1-3. (This minireview looked at the association between IUGR and future cardiovascular diseases. The researchers concluded that IUGR “favor[ed] the development of secondary cardiovascular diseases later in life.” They also concluded that an enriched understanding of cardiovascular diseases’ mechanisms would improve IUGR patients’ long-term outcomes.)  

 Priante, E., et al. "Intrauterine growth restriction: new insight from the metabolomic approach." Metabolites. 9.11. (2019): 267. (This study looked at metabolomic approaches to addressing IUGR’s clinical and pathophysiological aspects. The researchers intended to use these approaches to prevent or limit the condition’s long-term complications. They found that the preliminary reports suggested that IUGR neonates suffered from catabolite accumulation, glucose intolerance, insulin resistance, and altered amino acid metabolism. The researchers concluded that larger studies should be conducted to verify these results and clinically apply them.)