Investing in early life to promote health across the life course (Session)

Health and socioeconomic characteristics underlying educational attainment of children born preterm (James Boardman, UK)

Background

• In the UK, 27% of children live in poverty after housing costs, which is about 4.3 million children. That figure has risen since 2010. The EU’s at-risk-of-poverty-or-social-exclusion figures are similar on average, ranging from about 12% in Slovenia to about 35% in Bulgaria.

• In earlier work, his group used parent reports at age 2 to define four developmental clusters: typical, communication, neuromotor, and multiple problems. Neighbourhood deprivation at birth was among the top six predictors for every cluster. For the communication cluster it was the strongest predictor, ahead of all medical factors.

This study

• It is a new linkage between the National Neonatal Research Database (NNRD) and England’s National Pupil Database. The pupil database covers state-funded schools, which educate about 93% of children. This was a collaboration with Cheryl Battersby (Imperial College London).

• About 16,000 very preterm children were followed with six binary teacher-assessed outcomes from age 5 to 7:

  • school readiness at 5 (Early Years Foundation Stage Profile)

  • phonics screening at 6

  • reading, writing, maths and science at 7

Key findings

• 55.9% of very preterm children were not ready for school at 5. That is about 21 percentage points worse than the general population. Gaps in the other domains were 12 to 23 percentage points.

• There was a steep gestational age gradient. Almost 90% of 23-weekers were not school-ready, compared with just under 50% at 31 weeks.

• For 23–26 weeks, the most common pattern (29.5%) was not reaching the expected level in any domain between ages 5 and 7. The difficulties affect the whole classroom, not one subject.

• Deprivation and gestational age were additive. The curves ran in parallel and there was no statistical interaction. Deprivation hurts equally at every gestation.

• Mutually adjusted model:

  • Risk factors:

    • 23–25 weeks: OR about 2–3

    • most deprived neighbourhood: 20–40% higher risk

    • free school meal eligibility (a close proxy for family income): OR 1.72

    • maternal smoking

    • maternal diabetes

    • summer birth: strong effect at every age (in England, summer-born children are the youngest in their school year)

    • postnatal steroids. Given the era, these are mainly rescue steroids for severe lung disease or extubation, not low-dose prophylactic hydrocortisone.

    • NEC, BPD, sepsis, ROP

    • IVH grade 3–4 and PVL

    • any nutrition other than exclusive breast milk

  • Protective factors:

    • higher birth weight

    • female sex

    • antenatal steroids

  • No added risk:

    • IVH grade 1–2

  • Disadvantages that faded:

    • English as an additional language affected school readiness only and was gone by ages 6–7.

• 💡 Free school meal eligibility carried roughly the same risk as grade 3–4 IVH. Far more children are affected by the first than by the second.

Take-home messages

1. Prematurity and social disadvantage are a double burden. In no sense does prematurity override the social determinants.

2. Only gestational age, sex and season of birth are fixed. The rest can potentially be changed:

   • neighbourhood deprivation and family income

   • smoking in pregnancy

   • judicious corticosteroid use, both antenatal and postnatal

   • fewer brain injuries, cases of BPD, NEC and ROP

   • better nutrition, including breast milk

3. There may be a role for precision support before school entry. One example is boys born into deprivation in the summer months. This needs further research.

Q&A

• Person-centred or intersectional analyses? These are being considered in a deeply phenotyped cohort.

• Genetics? Boardman disputed that genetic risk for these outcomes is high in this population.

• ADHD and autism? New funding will map the age-2 clusters onto education. The communication cluster may include children later diagnosed with autism or ADHD.

🔹 Early growth trajectories and body composition in very preterm children: critical windows for fat-free mass accretion (Anna le Clercq, NL)

Why it matters

• Body composition, especially fat-free mass (FFM), may matter more than weight gain alone. FFM is linked to better neurodevelopment.

• Body composition is rarely measured in follow-up clinics, so a child can look fine on weight while lean mass accretion lags behind.

Study

• 1,402 children born at less than 30 weeks (median GA about 28 weeks, mean birth weight z-score about 0).

• Longitudinal weight z-scores from birth to 5.5 years.

• Two approaches:

  • Data-driven: latent class trajectories.

  • Hypothesis-driven: low FFM at 5.5 years (z-score < −1) compared with normal or high FFM, with growth looked at retrospectively.

Findings

• Two trajectories were found: stable and early reduced growth. Birth z-scores were similar. The groups diverged during the first ~2 years and ran in parallel afterwards.

• The reduced-growth group had lower FFM at 5.5 years.

• The hypothesis-driven approach showed the same pattern. Children with low FFM had a larger early postnatal fall in weight z-score and a weaker recovery. The difference came from weight-gain velocity in the first two years.

• Fat mass % did not differ. Both groups were below the population mean, so the better weight gain reflects lean tissue, not excess fat.

• GA, birth weight z-score and BPD did not modify these differences.

Take-home messages

• The first ~2 years after birth are a window to watch for later body composition.

• Whether nutritional or other interventions in this window can improve body composition, and in turn long-term health, is still to be tested.

Q&A

• Nutrition data were available at 2 years corrected age for about half the cohort and showed no difference. Clinical decisions such as adding nutritional support could not be captured, and may have been made for the slower-growing children.

• Which trajectory is better if weight at 5.5 years ends up similar? The authors hypothesise the higher-FFM group will do better neurodevelopmentally, but the cohort is too small to test IQ. There were no adverse cardiometabolic signs at 5.5 years. Follow-up continues.

🔹 Immune cross-talk between mother and baby – basis for longevity (Anke Diemert, Germany)

A maternal–fetal medicine view.

The fetal immune system develops in layers

• The fetal immune system is not simply “immature.” It builds up in overlapping waves of cell lineages from the yolk sac, liver and bone marrow. Some lineages exist only before birth.

• These cells shape immunity, barrier tissues and neurodevelopment.

• Preterm birth interrupts this process, and the consequences can be long-lasting.

Chronic maternal immune activation

• Stressors in modern pregnancies, such as high BMI, smoking, infections and lifestyle, drive chronic maternal immune activation.

• For the mother, this raises the risk of complications such as preeclampsia and hypertension.

• For the child, it reprograms the developing immune system. Examples given:

  • antenatal betamethasone affecting immune cell development

  • gestational diabetes and excess weight gain leading to a pro-inflammatory state in cord blood

  • preeclampsia associated with lower neutrophil counts and impaired neutrophil function

• Mode of birth also changes microbiome seeding.

Windows of opportunity

• Vaccination in pregnancy

• Appropriate gestational age at birth

• Optimising how antibodies are transferred

• Reducing harmful exposures

Maternal vaccination

• Maternal vaccination bridges the newborn’s susceptibility gap. Placental IgG transfer through the FcRn receptor is active, so cord IgG can reach about 120–150% of maternal levels.

• Some vaccines protect mostly the mother (for example influenza), which also helps prevent iatrogenic preterm delivery.

• Others are aimed mainly at the baby: pertussis and RSV.

New data from her cohort

• Mothers vary a lot in how efficiently they transfer IgG to the baby, even after correcting for GA.

• Each mother’s transfer efficiency stays the same in her next pregnancy. This individual variation is not currently taken into account.

Turning transfer off

• FcRn antagonists block transfer of harmful IgG to the fetus. They are being tested in randomised double-blind trials for:

  • HDFN (haemolytic disease of the fetus and newborn)

  • FNAIT (fetal and neonatal alloimmune thrombocytopenia)

Take-home message: Immune programming for lifelong health starts before birth. Learning how to modulate mother–baby immune cross-talk is a frontier for both obstetrics and neonatology.

Disclosure: This is an AI-assisted summary of the session, generated from a recording made by our team in attendance. We believe it is as accurate as our own notes would be, but please refer to the speakers’ original work before applying anything in clinical practice.