Defining poor growth and stillbirth risk in pregnancy for infants of mothers with overweight and obesity.

BACKGROUND: Mothers who are obese carry heavier fetuses and have lower rates of small for gestational age (<10th birthweight centile) infants. However, their infants may be growth-restricted (with an increased risk of stillbirth) at a higher birthweight centile compared with infants from healthy-weight women. OBJECTIVE: This study aimed to quantify the birthweight centile at which the risk of stillbirth in infants born to obese women equaled that of <10th-centile infants born to healthy-weight women, and clarify the relationship between maternal body mass index, infant size, and stillbirth. STUDY DESIGN: We conducted a retrospective cohort study on all infants born in Victoria, Australia, from 2009 to 2019 (754,946 cases for analysis). We applied uncustomized birthweight centiles to all infants, and stratified the maternal cohort by body mass index (<20 kg/m2, 20-25 kg/m2, 25-30 kg/m2, 30-35 kg/m2, 35-40 kg/m2, ≥40 kg/m2). For each body mass index category, we assessed proportions of infants born <10th centile and <3rd centile, stillbirth rates among infants of all sizes, and small for gestational age infants. We calculated the stillbirth rate (per 1000) and relative risk (risk of stillbirth if born <10th centile vs >10th centile) for healthy-weight women (body mass index, 20-25 kg/m2). We then determined the birthweight centile for infants born to mothers within other body mass index categories that equaled that rate or risk. RESULTS: Stillbirth rates increased with increasing maternal body mass index. Infants classified as small for gestational age (<10th centile) from mothers with high body mass index had a higher risk of stillbirth (relative risk, 3.15; 95% confidence interval, 2.22-4.47; for mothers with body mass index ≥40 kg/m2 vs healthy-weight mothers [body mass index, 20-25 kg/m2]). The stillbirth rate (stillborn infants per 1000 births) among <10th-centile infants born to healthy-weight mothers was 7.5 per 1000. The same stillbirth rate was observed at higher birthweight centiles for infants of women with higher body mass index (<18th centile for those with a body mass index of 25-30 kg/m2, <25th centile for body mass index of 30-35 kg/m2, <31st centile for body mass index of 35-40 kg/m2, <41st centile for body mass index of ≥40 kg/m2). The relative risk of stillbirth among small for gestational age infants of healthy-weight mothers was 5.46 (95% confidence interval, 4.65-6.40). The birthweight centile with a comparable relative risk of stillbirth increased with increasing body mass index (<16th centile for women with body mass index of 25-30 kg/m2, <19th centile for body mass index of 30-35 kg/m2, <28th centile for body mass index of 35-40 kg/m2, <30th centile for body mass index ≥40 kg/m2). CONCLUSION: Obesity affects the relationship between infant size and perinatal mortality. The stillbirth risk observed in <10th-centile infants from healthy-weight mothers occurs at higher birthweight centiles with overweight or obese mothers. Clinicians should be aware that the same infant risk exists at a higher birthweight centile for women with higher body mass index.

Adjusting growth standards for fetal sex improves correlation of small babies with stillbirth and adverse perinatal outcomes: A state-wide population study.

OBJECTIVES: Sex impacts birthweight, with male babies heavier on average. Birthweight charts are thus sex specific, but ultrasound fetal weights are often reported by sex neutral standards. We aimed to identify what proportion of infants would be re-classified as SGA if sex-specific charts were used, and if this had a measurable impact on perinatal outcomes. METHODS: Retrospective cohort study including all infants born in Victoria, Australia, from 2005-2015 (529,261 cases). We applied GROW centiles, either adjusted or not adjusted for fetal sex. We compared overall SGA populations, and the populations of males considered small by sex-specific charts only (SGAsex-only), and females considered small by sex-neutral charts only (SGAunadjust-only). RESULTS: Of those <10th centile by sex-neutral charts, 39.6% were male and 60.5% female, but using sex-specific charts, 50.3% were male and 49.7% female. 19.2% of SGA females were reclassified as average for gestational age (AGA) using sex-specific charts. These female newborns were not at increased risk of stillbirth, combined perinatal mortality, NICU admissions, low Apgars or emergency CS compared with an AGA infant, but were at greater risk of being iatrogenically delivered on suspicion of growth restriction. 25.0% male infants were reclassified as SGA by sex-specific charts. These male newborns, compared to the AGAall infant, were at greater risk of stillbirth (RR 1.94, 95%CI 1.30-2.90), combined perinatal mortality (RR 1.80, 95%CI 1.26-2.57), NICU admissions (RR 1.38, 95%CI 1.12-1.71), Apgars <7 at 5 minutes (RR 1.40, 95%CI 1.25-1.56) and emergency CS (RR 1.12, 95%CI 1.06-1.18). CONCLUSIONS: Use of growth centiles not adjusted for fetal sex disproportionately classifies female infants as SGA, increasing their risk of unnecessary intervention, and fails to identify a cohort of male infants at increased risk of adverse outcomes, including stillbirth. Sex-specific charts may help inform decisions and improve outcomes.

Fetal size classified using gestational days rather than gestational weeks improves correlation with stillbirth risk: A statewide population study.

OBJECTIVE: Many growth charts provide single centile cutoffs for each week of gestation, yet fetuses gain weight throughout the week. We aimed to assess whether using a single centile per week distorts the proportion of infants classified as small and their risk of stillbirth across the week. DESIGN: Retrospective cohort study. SETTING: Victoria, Australia. POPULATION: Singleton, non-anomalous infants born from 2005-2015 (529,261). METHODS: We applied growth charts to identify small-for-gestational-age (SGA) fetuses on week-based charts (single centile per gestational week) and day-based charts (centile per gestational day). MAIN OUTCOME MEASURES: Proportions <10th centile by each chart, and stillbirth risk amongst SGA infants. RESULTS: Using week-based charts, 12.1% of infants born on the first day of a gestational week were SGA, but only 7.8% on the final day; ie. an infant born at the end of the week was 44% less likely to be classed as SGA (p<0.0001). The relative risk of stillbirth amongst SGA infants born on the final day of the week compared with the first was 1.47 (95%CI 1.09-2.00, p = 0.01). Using day charts, SGA proportions were similar and stillbirth risk equal between the beginning and end of the week (9.5% vs 9.9%). CONCLUSIONS: Growth standards using a single cutoff for a gestational week overestimate the proportion of infants that are small at the beginning of the week and underestimate the proportion at the end. This distorts the risk of stillbirth amongst SGA infants based on when in the week an infant is born. Day-based charts should be used.

Risk of major labour-related complications for pregnancies progressing to 42 weeks or beyond.

BACKGROUND: Post-term gestation beyond 41+6 completed weeks of gestation is known to be associated with a sharp increase in the risk of stillbirth and perinatal mortality. However, the risk of common adverse outcomes related to labour, such as shoulder dystocia and post-partum haemorrhage for those delivering at this advanced gestation, remains poorly characterised. The objective of this study was to examine the risk of adverse, labour-related outcomes for women progressing to 42 weeks gestation or beyond, compared with those giving birth at 39 completed weeks. METHODS: We performed a state-wide cohort study using routinely collected perinatal data in Australia. Comparing the two gestation cohorts, we examined the adjusted relative risk of clinically significant labour-related adverse outcomes, including macrosomia (≥ 4500 at birth), post-partum haemorrhage (≥1000 ml), shoulder dystocia, 3rd or 4th degree perineal tear and unplanned caesarean section. Parity, maternal age and mode of birth were adjusted for using logistic regression. RESULTS: The study cohort included 91,314 women who birthed at 39 completed weeks and 4317 at ≥42 completed weeks. Compared to 39 weeks gestation, those giving birth ≥42 weeks gestation had an adjusted relative risk (aRR) of 1.85 (95% CI 1.55-2.20) for post-partum haemorrhage following vaginal birth, 2.29 (95% CI 1.89-2.78) following instrumental birth and 1.44 (95% CI 1.17-1.78) following emergency caesarean section; 1.43 (95% CI 1.16-1.77) for shoulder dystocia (for non-macrosomic babies); and 1.22 (95% CI 1.03-1.45) for 3rd or 4th degree perineal tear (all women). The adjusted relative risk of giving birth to a macrosomic baby was 10.19 (95% CI 8.26-12.57) among nulliparous women and 4.71 (95% CI 3.90-5.68) among multiparous women. The risk of unplanned caesarean section was 1.96 (95% CI 1.86-2.06) following any labour and 1.47 (95% CI 1.38-1.56) following induction of labour. CONCLUSIONS: Giving birth at ≥42 weeks gestation may be an under-recognised risk factor for several important, labour-related adverse outcomes. Clinicians should be aware that labour at this advanced gestation incurs a higher risk of adverse outcomes. In addition to known perinatal risks, the risk of obstetric complications should be considered in the counselling of women labouring at post-term gestation.

Identification of the optimal growth charts for use in a preterm population: An Australian state-wide retrospective cohort study.

BACKGROUND: Preterm infants are a group at high risk of having experienced placental insufficiency. It is unclear which growth charts perform best in identifying infants at increased risk of stillbirth and other adverse perinatal outcomes. We compared 2 birthweight charts (population centiles and INTERGROWTH-21st birthweight centiles) and 3 fetal growth charts (INTERGROWTH-21st fetal growth charts, World Health Organization fetal growth charts, and Gestation Related Optimal Weight [GROW] customised growth charts) to identify which chart performed best in identifying infants at increased risk of adverse perinatal outcome in a preterm population. METHODS AND FINDINGS: We conducted a retrospective cohort study of all preterm infants born at 24.0 to 36.9 weeks gestation in Victoria, Australia, from 2005 to 2015 (28,968 records available for analysis). All above growth charts were applied to the population. Proportions classified as <5th centile and <10th centile by each chart were compared, as were proportions of stillborn infants considered small for gestational age (SGA, <10th centile) by each chart. We then compared the relative performance of non-overlapping SGA cohorts by each chart to our low-risk reference population (infants born appropriate size for gestational age [>10th and <90th centile] by all intrauterine charts [AGAall]) for the following perinatal outcomes: stillbirth, perinatal mortality (stillbirth or neonatal death), Apgar <4 or <7 at 5 minutes, neonatal intensive care unit admissions, suspicion of poor fetal growth leading to expedited delivery, and cesarean section. All intrauterine charts classified a greater proportion of infants as <5th or <10th centile than birthweight charts. The magnitude of the difference between birthweight and fetal charts was greater at more preterm gestations. Of the fetal charts, GROW customised charts classified the greatest number of infants as SGA (22.3%) and the greatest number of stillborn infants as SGA (57%). INTERGROWTH classified almost no additional infants as SGA that were not already considered SGA on GROW or WHO charts; however, those infants classified as SGA by INTERGROWTH had the greatest risk of both stillbirth and total perinatal mortality. GROW customised charts classified a larger proportion of infants as SGA, and these infants were still at increased risk of mortality and adverse perinatal outcomes compared to the AGAall population. Consistent with similar studies in this field, our study was limited in comparing growth charts by the degree of overlap, with many infants classified as SGA by multiple charts. We attempted to overcome this by examining and comparing sub-populations classified as SGA by only 1 growth chart. CONCLUSIONS: In this study, fetal charts classified greater proportions of preterm and stillborn infants as SGA, which more accurately reflected true fetal growth restriction. Of the intrauterine charts, INTERGROWTH classified the smallest number of preterm infants as SGA, although it identified a particularly high-risk cohort, and GROW customised charts classified the greatest number at increased risk of perinatal mortality.