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Examining the growing body of evidence on foetal growth

Is my baby normal?’ is a common question faced by any obstetrician and is usually followed by a ‘how big is s/he now?’ enquiry. Yet few of us consider exactly how the lines measured on an ultrasound screen translate into kilos and grams in a predicted weight. Fewer still consider how differences in maternal characteristics can influence these calculations. A major international conference held in Cork recently put this question to the experts. ‘Fetal Growth’ is in its sixth year and brings together researchers from areas of obstetrics, neonatology, epidemiology, public health and statistics. The two-day conference had a focus on the use of standardised centile charts to accurately assess a baby’s growth in utero, along with the causes and management of foetal growth restriction and stillbirth.

To understand ultrasound prediction of foetal weight, we must go back to the 1980s. We take it for granted these days that we can accurately measure foetal weight by measuring various parts of a baby on an ultrasound screen. In the early 1980s, several competing groups developed formulae for estimating foetal weight and checked their accuracy in the days following birth. Ironically, the person who contributed most to this branch of obstetrics was not an obstetrician, but a radiologist called Frank P Hadlock of Houston, Texas. Prof Hadlock had a special interest in the emerging field of ultrasound in pregnancy and published a seminal series of papers on foetal growth measurements and foetal abnormalities in the 1980s. His measurement formulae are still used in the software of ultrasound machines today to estimate foetal weight.

Research

Later, researchers such as those at the World Health Organisation (WHO) developed centile charts to score foetal growth against a standardised ‘normal’ foetus, and thus provide information on whether a baby has normal growth.

However, foetal growth and birth weight are not necessarily the same thing and a preterm baby has a different growth pattern to a baby still in utero. Using a foetal growth standard to assess a preterm baby’s growth is therefore problematic, particularly if this is a baby in the developing world. The WHO birth weight estimates were based on a population of births in California in the 1970s — typically a white, middle-class mother who may or may not have smoked.

This is very different to today’s mother, 40 years later — especially when that mother is African, Indian or Asian. Population studies of these women have shown significant differences from the typical WHO mother. Using the wrong centile chart in pregnancy can potentially lead to an incorrect diagnosis of intrauterine growth restriction — and unnecessary intervention for a normal baby incorrectly labelled as ‘small’. 

One of the largest projects to date to formulate new population charts is the Bill and Melinda Gates Foundation ‘International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21ST).’ This global collaboration of over 80 investigators aimed to provide an estimate of baby growth in eight geographically-distinct regions spanning North and South America, Europe, Africa, Western Asia and the Indian subcontinent. The premise is that if all other conditions are optimal, INTERGROWTH-21ST would be a single international reference of the best growth a baby could achieve. Foetal growth restriction can have a devastating impact on a baby, both in terms of brain growth and in long-term neurodevelopmental outcomes. When these babies are delivered early, they have the added issue of prematurity and long stays in a neonatal intensive care unit. A baby weighing between 2.0-to-2.5kg is 2.8 times more likely to die in the neonatal period than a baby weighing over 2.5kg. Out of 125 million births globally each year, approximately 20 million babies are of low birth weight — that is, they weight less than 2.5kg. This represents 16 per cent of global births but the developing world is disproportionately represented, with 95 per cent of these small babies delivering in a developing country. More than two-thirds of low-birth-weight babies have signs of intra-uterine growth restriction, particularly in South Central Asia, where a staggering one-quarter of babies are of low birth weight. The causes of these population-wide features are a combination of genetics, malnutrition, environmental exposures, poor access to healthcare and maternal infections.

Conference

These problems were at the heart of the Cork conference programme — 240 delegates from 26 countries descended on Fota Island Resort Hotel for two days of animated debate. The format of keynote speakers headlining a topic, followed by oral presentations of local and international research, gave a feel for the breadth of research being presented. Almost immediately, issues with the new INTERGROWTH-21ST centiles were at the forefront of discussion, with researchers from both Europe and America highlighting that INTERGROWTH-21ST results in lower proportions of small for gestational age (SGA) babies. This could potentially mislabel a small baby as ‘normal’, unless there is a different local percentile cut-off used to identify babies at risk. Research was also presented on WHO-based growth charts and local GROW (Gestation Related Optimal Weight) charts customised for maternal characteristics such as height, weight, parity and ethnic origin. The use of GROW software in Birmingham is thought to have resulted in a reduction in stillbirths in the north-east of England. When compared to INTERGROWTH-21ST, being SGA using GROW software was more sensitive for identification of placental pathology in pregnancies that end in late stillbirth, giving an indication of what is at stake when using different charts.

Moving on from centiles and graphs, Prof Leslie McGowan of the University of Auckland, New Zealand, gave a keynote address on causes of foetal growth restriction, with a particular focus on smoking. Smoking remains the single largest modifiable risk factor for foetal growth restriction. In higher-income countries, the rate of smoking in both the general population and in pregnancy is declining. However, this decline is uneven, with higher rates of smoking still encountered in lower socioeconomic groups. Prof McGowan urged continued population-level interventions to reduce cigarette consumption, in addition to individual interventions with the women themselves.

Irish contribution

Research on the placenta as a witness to foetal growth restriction and stillbirth was presented by several groups. Dr Brendan Fitzgerald, Consultant Histopathologist and Specialist in Perinatal Pathology at Cork University Hospital, gave a keynote address on the placenta in early- and late-onset growth restriction, with Dr Khadijah Ismail of the University of Limerick winning Best Poster for her presentation on the link between placental morphology and stillbirth. In general, Irish research was well represented at the conference. Dr Helena Bartels of the National Maternity Hospital, Holles Street, presented data from a secondary analysis of the ‘Low glycaemic index diet in pregnancy to prevent macrosomia’ — the ROLO study. This found that foetal growth trajectories were significantly associated with both maternal BMI and maternal glucose levels, with potential implications for intervention in pregnancy and BMI in childhood.

Midwife Ms Grainne Milne of Our Lady of Lourdes Hospital, Drogheda, discussed the unit’s experience with the implementation of customised GROW charts to reduce stillbirth rates, while Dr Paul Corcoran of the National Perinatal Epidemiology Centre in Cork presented national audit data, which revealed poor detection rates of SGA babies among stillbirths. Dr Fionnuala Mone of the Perinatal Research Centre, School of Medicine, University College Dublin and the National Maternity Hospital, presented feasibility data from the ‘TEST’ trial — a new, randomised, controlled trial on the use of aspirin with an early screening test for pre-eclampsia in low-risk women.

Big babies

The penultimate keynote presentations were on patterns of growth in twins and the increasing problem of ‘big babies’. Dr Katherine Grantz of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), US, presented research from their twin growth study. This revealed that twin growth trajectories are different from singletons, particularly from 32 weeks’ gestation onwards. As this is often thought to be a normal adaptation of twin pregnancies to a smaller intrauterine environment, Dr Grantz called for an ultrasound reference specifically for twins to avoid unnecessary intervention.

Dr Katie Cresswell of North Middlesex University Hospital, UK, discussed the problem of macrosomia — big babies. Predicted big babies in their unit had led to a significant increase in elective Caesarean sections by maternal request, which is problematic, as many of these women would potentially have had successful and safe vaginal deliveries. This is particularly relevant considering the landmark Montgomery ruling on informed consent in the UK in 2015, which has led to discussion of all possible negative consequences of vaginal delivery in these situations. 

The conference was closed with a keynote presentation on ‘Perinatal Ireland’ from Dr Alyson Hunter of the Royal Jubilee Maternity Hospital, Belfast. Perinatal Ireland is a research collaboration between seven of Ireland’s largest maternity units — Rotunda, Coombe and National Maternity Hospital, Dublin, Cork, Limerick, Galway and Belfast. The Perinatal Ireland research consortium has published extensively on the use of ultrasound as a predictor of perinatal outcomes. Their research includes the ESPRIT twin study, which examined twin growth discrepancies and mode of delivery; the PORTO foetal growth study, which examined identification and monitoring of small babies most at risk from foetal growth restriction; and the GENESIS study, which examined head circumference at term and birth outcomes.

Dr Hunter highlighted the advantages of working in such a collaborative research setting to the international audience present, and the conference concluded with a debate on what research is needed next to secure the futures of small babies everywhere.

The sixth International Conference on Fetal Growth 2017 took place in Fota Island, Cork, from 20-22 September 2017.

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