Intrauterine growth discordance across gestation and birthweight discordance in dichorionic twins

Abstract

Background: Although intertwin size difference is an important measure of fetal growth, the appropriate cut point to define discordance is unclear. Few studies have assessed intertwin differences in estimated fetal weight longitudinally or in relation to size differences at birth.

Objectives: The objectives of the study were to estimate the magnitude of percentage differences in estimated fetal weight across gestation in dichorionic twins in relation to a fixed discordance cut point and compare classification of aberrant fetal growth by different measures (estimated fetal weight differences, birthweight discordance, small for gestational age).

Study design: Women aged 18-45 years from 8 US centers with dichorionic twin pregnancies at 8 weeks 0 days to 13 weeks 6 days gestation planning to deliver in participating hospitals were recruited into the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Dichorionic Twins study and followed through delivery (n = 140; 2012-2013). Ultrasounds were conducted at 6 targeted study visits to obtain fetal biometrics and calculate estimated fetal weight. Percent estimated fetal weight and birthweight differences were calculated: ([weightlarger - weightsmaller]/weightlarger)*100; discordance was defined as ≥18% for illustration. Birth sizes for gestational age (both, 1, or neither small for gestational age) were determined; twins were categorized into combined birthweight plus small for gestational age groups: birthweight discordance ≥18% (yes, no) with both, 1, or neither small for gestational age. Linear mixed-models estimated percentiles of estimated fetal weight percent differences across gestation and compared estimated fetal weight differences between combined birthweight discordance and small for gestational age groups. A Fisher exact test compared birthweight discordance and small for gestational age classifications.

Results: Median estimated fetal weight percentage difference increased across gestation (5.9% at 15.0, 8.4% at 38.0 weeks), with greater disparities at higher percentiles (eg, 90th percentile: 15.6% at 15.0, 26.3% at 38.0 weeks). As gestation advanced, an increasing percentage of pregnancies were classified as discordant using a fixed cut point: 10% at 27.0, 15% at 34.0, and 20% at 38.0 weeks. Birthweight discordance and small for gestational age classifications differed (P = .002); for birthweight discordance ≥18% vs <18%: 44% vs 71% had neither small for gestational age; 56% vs 18% had 1 small for gestational age; no cases (0%) vs 11% had both small for gestational age, respectively. Estimated fetal weight percent difference varied across gestation by birthweight discordance plus small for gestational age classification (P = .040). Estimated fetal weight percentage difference increased with birthweight discordance ≥18% (neither small for gestational age: 0.46%/week [95% confidence interval, 0.08-0.84]; 1 small for gestational age: 0.57%/week [95% confidence interval, 0.25-0.90]) but less so without birthweight discordance (neither small for gestational age: 0.17%/week [95% confidence interval, 0.06-0.28]; 1 small for gestational age: 0.03%/week [95% confidence interval, -0.17 to 0.24]); both small for gestational age: 0.10%/week [95% confidence interval, -0.15 to 0.36]).

Conclusion: The percentage of dichorionic pregnancies exceeding a fixed discordance cut point increased over gestation. A fixed cut point for defining twin discordance would identify an increasing percentage of twins as discordant as gestation advances. Small for gestational age and percentage weight differences assess distinct aspects of dichorionic twin growth. A percentile cut point may be more clinically useful for defining discordance, although further study is required to assess whether any specific percentile cut point correlates to adverse outcomes.

Trial registration: ClinicalTrials.gov NCT01369940.

Keywords: dichorionic; estimated fetal weight; fetal growth; small for gestational age; twin.

Conflict of interest statement

Conflicts of Interest: The authors report no conflict of interest.

Published by Elsevier Inc.

Figures

Figure 1:

Participant flow diagram (N=140; NICHD Fetal Growth Studies--Dichorionic Twins, USA, 2012–13) Retention of women in this secondary analysis of NICHD Fetal Growth Studies--Dichorionic Twins. Participants were followed until occurrence of an event (e.g., delivery, deactivation). Delivery data from chart abstraction was available for n=137 women (n=1 with no delivery data; n=2 with partial delivery data due to delivery at a non-participating hospital). Following visit 6, n=2 live births ≥20 weeks one twin, fetal deaths ≥20 weeks one twin occurred. Numbers in parentheses represent women missing data for that visit †Mean gestational age (range) for women with percent difference in estimated fetal weight for that visit

Figure 2:

Distribution of inter-twin percent differences in estimated fetal weight across gestation among dichorionic twin pregnancies (N=140; NICHD Fetal Growth Studies--Dichorionic Twins, USA, 2012–13) Estimated 10th, 25th, 50th, 75th, 80th, 85th, 90th percentiles of inter-twin percent differences in estimated fetal weight among dichorionic twins, as estimated by linear mixed models with random slopes and intercepts, centered at 15 weeks. Percentiles plotted in relation to an 18% cut-point to define clinically significant discordance (horizontal black line) to demonstrate impact of using a fixed cut-point across gestation to define discordance.

Figure 3:

Percent difference in EFW* by combined birth size at gestational age†+birthweight discordance‡ group (NICHD Fetal Growth Studies--Dichorionic Twins, USA, 2012–13) Abbreviations: BW, birthweight; EFW, estimated fetal weight; GA, gestational age; SGA, small for GA Percent difference in EFW across gestation differed by combined birth size at GA+BW discordance group (p=0.040), but not at 15 weeks gestation. A statistically significant pairwise difference in percent difference in EFW across gestation was found between the BW concordant+neither SGA group (reference group; 0.17% per week, 95% CI 0.056, 0.28) and the BW discordant+1 twin SGA group (0.57% per week, 95% CI 0.25, 0.90; p=0.020). Estimates used to create figure derived from an unadjusted linear mixed model with random slopes and intercepts (centered at 15 weeks). *Percent difference in weight (EFW or BW; %)=([Weightlarger twin- Weightsmaller twin]/Weightlarger 598 twin)*100 †Birth size for GA of each twin was determined based on GA at delivery and neonatal sex specific percentiles (n=132; missing n=8 [n=5 GA<24 weeks, n=3 no BW]) ‡BW discordance: categorized as concordant (<18% difference in BW) or discordant (≥18% difference in BW) based on a prospective study which found BW differences exceeding 18% may be pathologic