You are asked to see a baby boy in the labour ward.
He was born at 38 weeks and 5 days gestational age and weighs 2600 grams.
His mother is healthy, but she does mention that her first-born daughter was also small. She weighed 2570 grams at 39 weeks and is now perfectly healthy.
The parents are of South-Asian descent. There were no issues during the pregnancy, and estimated fetal growth by ultrasound was constant.
According to the Obstetric resident, the placenta looked a little small.
Fetal Growth Restriction (FGR) and dysmaturity are common in neonatology and are a leading cause of morbidity during the neonatal period and later in life. However, there are no agreed-upon definitions for growth restriction and significant knowledge gaps. In everyday medical practice, it is sometimes difficult to pinpoint the cause of the growth restriction. In our example, you might wonder whether this child is growth-restricted or small for gestational age (SGA). The latter carries little risk of long-term consequences. Do heritage and the fact that his sister was SGA suggest that the child is just constitutionally small? Or do they both share another risk factor for FGR?
Definitions and diagnosis of fetal growth restriction
The most common definition used to define SGA refers to a group of neonates weighing less than a certain percentile of the normal weight distribution in a population for a given gestational age. The centile used to define “small” may differ both by scientific study and by hospital. We commonly use less than the tenth centile.
Generally, boys and girls yield different weight curves, and more distinctions can be made (e.g., the first-born child versus multiparity and by ethnicity). It is useful to know that there are two kinds of weight curves:
Descriptive, in which nearly all mothers and their children are included with few exclusion criteria, and
Prescriptive, in which groups of women with pathologies that affect neonatal morbidity and mortality outcomes have been excluded. For example, women who smoke are more likely to have SGA babies.
There is some evidence that prescriptive weight curves, by omitting greater groups of women, are better at predicting future morbidity than descriptive curves. However, they may also lead to overdiagnosis, as healthy children may be categorized as small.
Growth retardation (FGR) is usually defined as fetuses who experience a decline in (estimated) weight or abdominal circumference of more than 20 percentile points over two weeks or more. Babies who experienced fetal growth restriction while in utero may be more at risk for morbidity/mortality than SGA babies with no concomitant pathologies and no signs of malnourishment, who have reached their full growth potential, and who are just small.
It is possible to have been growth restricted while still having a weight considered appropriate for gestational age! In other words, not all SGA babies experienced growth restriction, and not all growth-restricted neonates are SGA.
Fetal Growth Restriction can be divided into early (<32 weeks) and late (>32 weeks). It can also be divided into symmetric (in which all anthropometric measures are small) and asymmetric (in which the head circumference is normal, but other measures have gradually declined). It is thought that symmetric FGR occurs in early pregnancy and asymmetric later on, but this difference is not absolute.
There is currently no easy way to identify FGR and/or SGA babies at risk of future complications. Refer to your local or national guidelines to decide whether a patient is SGA, but remember that, depending on which definition is used, over- and underdiagnosis can occur.
Differential diagnosis of small babies
The differential diagnosis for SGA and growth-restricted babies is extensive:
The diagnosis of growth restriction in utero has improved because of the better use of ultrasound but still remains challenging. After birth, a good maternal and obstetric history and a physical examination may point to the cause, but it is often difficult to be certain.
Growth-restricted babies often have an “old man-look”, increased skin desquamation and shedding, with loose skin, a lack of subcutaneous fat, a relatively big anterior fontanelle, and an immature aspect of the female genitalia.
Ask about placental abnormalities and, if necessary, send the placenta for pathological analysis.
Think about possible signs of infection that might have caused FGR. Look for microcephaly, petechiae, hepatosplenomegaly, cardiological problems, blueberry muffin spots, and cataracts. If you suspect an infection, you can send in maternal blood for TORCHes, but the results are not always clear-cut. If there are dysmorphic features, it might be worth enlisting the help of a geneticist. You could consider a cranial ultrasound, cytomegalovirus PCR, and maternal toxicology screening.
Potential consequences of fetal growth restriction
Short-term
- Preterm birth (sometimes iatrogenic)
- Hypo- and hyperglycaemia
- Jaundice and cholestasis
- Hypocalcaemia, hypophosphatemia
- Early or late-onset sepsis
- Thrombocytopaenia and polycythaemia
- Impaired temperature regulation
- Necrotising enterocolitis
- Meconium aspiration syndrome
- Respiratory distress syndrome
- Persistent pulmonary hypertension of the newborn
- Asphyxia
- Intra-ventricular haemorrhage
- Constipation / not passing stools within 48 hours
- SGA babies are at 2 – 8x higher risk of mortality than children with appropriate weight
Long-term consequences
- Bronchopulmonary dysplasia (in combination with prematurity)
- Bronchiolitis and Asthma
- Neurodevelopmental problems such as cerebral palsy
- Behavioural and learning problems
- Obesity, metabolic syndrome, and associated insulin resistance
- Diabetes
- Dyslipidaemia
- Hypertension
- Cardiovascular disease (due to vascular remodelling and aforementioned problems)
- Kidney problems (growth-restricted children have fewer nephrons)
Some of these long-term consequences of FGR may relate to epigenetic changes in the fetus’s DNA. Poor nutrition during pregnancy may pre-dispose the fetus to chronic disease in later life – the so-called Barker hypothesis.
Treatment
Preventing growth restriction is hard and depends on the cause. Similarly, treatment depends on the problems that arise.
- Hypothermia should be prevented both directly after birth (this includes considering the use of polythene bags in very small neonates born >32 weeks) and during admission.
- There is an increased risk of persistent pulmonary hypertension of the newborn (PPHN). This should be treated accordingly.
- Enteral feeds (preferably breast milk) should be started early, but volumes should be increased carefully. SGA babies may depend on parenteral and/or nasogastric tube feeding for longer periods
- Depending on the situation, Hypoglycaemia should be corrected using oral feeds, dextrose gel, or intravenous glucose.
- Severe hypophosphatemia and hypocalcaemia should be corrected
- Severe polycythaemia should be corrected
- An enema may treat constipation if they haven’t passed stools after 48 hours.
Literature list
Beune IM et al. Consensus-based definition of growth restriction in the newborn. J Pediatr 2018;196:71-6.
Burchard PR et al. Glycerin suppositories and enemas in premature infants: a meta-analysis. Pediatrics 2022;149:e2021053413.
Colella M et al. Neonatal and long-term consequences of fetal growth restriction. Curr Pediatr Rev 2018;14:212–8.
de Boo HA & Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust N Z J Obstet Gynaecol 2006;46:4-14.
Francis J et al. Perinatal mortality by birthweight centile. ANZJOG 2014;54:354-9.
Gordijn SJ et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol 2016;48:333-9.
Hoftiezer L et al. Defining small-for-gestational-age: prescriptive versus descriptive birthweight standards. Eur J Pediatr 2016;175:1047-57.
Hoftiezer L et al. Prescriptive birthweight charts can improve the prediction of adverse outcomes in very preterm infants who are small for gestational age. Acta Pediatrica 2018;107:981-9.
Mandy GT. Infants with fetal (intrauterine) growth restriction. Up To Date, https://www.uptodate.com/contents/infants-with-fetal-intrauterine-growth-restriction Accessed on: 11 August 2022.
Roseboom T et al. The Dutch famine and its long-term consequences for adult health. Early Hum Dev 2006;82:485-91.
Thornton PS et al. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 2015;167:238-45.
