Growth restriction in gastroschisis: quantification of its severity and exploration of a placental cause

Abstract

Background: Gastroschisis patients are commonly small for gestational age (SGA, birth weight [BW] < 10th centile). However, the extent, symmetry and causes of that growth restriction remain controversial.

Methods: We compared BW, crown-heel length (LT), occipitofrontal circumference (OFC) and ponderal index (PI) in 179 gastroschisis cases and 895 matched controls by univariate and multiple regression. Fetal ultrasounds (N = 80) were reviewed to determine onset of growth restriction. Placental histology was examined in 31 gastroschisis patients whose placental tissue was available and in 29 controls.

Results: Gastroschisis cases weighed less than controls (BW = 2400 ± 502 g vs. 2750 ± 532 g, p < 0.001) and their BW frequency curve was shifted to the left, indicating lower BW as a group compared to controls (p < 0.001 by Kolmogorov-Smirnov test). BW differences varied from -148 g at 33 weeks to -616 g at 38 weeks gestation. Intrauterine growth restriction was symmetric with gastroschisis patients having a shorter LT (45.7 ± 3.3 vs. 48.4 ± 2.7 cm, p < 0.001), smaller OFC (31.9 ± 1.9 vs. 32.9 ± 1.6 cm, p < 0.001), but larger ponderal index (2.51 ± 0.37 vs. 2.40 ± 0.16, p < 0.001) compared to controls. Gastroschisis patients had a similar reduction in BW (-312 g, 95% confidence interval [CI] = -367, -258) compared to those with chromosomal abnormalities (-239 g, CI = -292, -187). Growth deficits appeared early in the second trimester and worsened as gestation increased. Placental chorangiosis was more common in gastroschisis patients than controls, even after removing all SGA patients (77% vs. 42%, p = 0.02).

Conclusions: Marked, relatively symmetric intrauterine growth restriction is an intrinsic part of gastroschisis. It begins early in the second trimester, and is associated with placental chorangiosis.

Figure 1

Flow diagram showing the total study population, exclusions, and final sample sizes. Percentages are calculated using the total number of available patients before exclusions.

Figure 2

The percent of SGA infants (birth weight <10^th centile) by maternal age group in gastroschisis cases (black bars) and controls (gray bars). For neither gastroschisis nor controls was the rate of SGA significantly different among the maternal age groups (p = 0.931 and p = 0.326, respectively by Fisher exact test).

Figure 3

Frequency line graphs of the birth weight distribution of gastroschisis cases (black line) and controls (gray line). Kolmogorov-Smirnov test confirmed that this difference was significant (p < 0.001).

Figure 4

Generalized Lorenz graphs of the birth weight for gastroschisis cases (black line) and controls (interrupted gray line). The X-axis represents the proportion of the population of both cases and controls. The Y-axis represents the cumulative mean birth weight, calculated as cumulative birth weight at the given proportion of the population divided by the total population. These curves are a measure birth weight distribution and indicate gastroschisis cases have a lower cumulative mean birth weight at almost all proportions of the study sample.

Figure 5

Adjusted mean BW of gastroschisis cases (black line) and controls (gray line) by gestational age with the 95% confidence intervals represented by the error bars. The 10^th and 50^th centiles were obtained from published standards[24]. BW was adjusted using the regression equation from Table 2 and included maternal race, cigarette smoking, GHP, recreational drug use, previous pregnancies and inborn status. From 33 weeks to about 38 weeks gestation, gastroschisis cases weighed progressively less than controls, changing from -148 grams to -616 grams. The percentage of BW deficit in gastroschisis cases increased from 7% at 33 weeks gestation to 18% at 38 weeks. The small number of patients available for analysis prior to 33 and after 38 weeks resulted in wide confidence intervals and potentially unreliable estimates.

Figure 6

Figure 6. A 10× photomicrograph of chorangiosis in a placenta from a woman who delivered a patient with gastroschisis. The arrow points to an area with multiple vascular channels. Diffuse chorangiosis was defined as ≥ 10 capillaries in ≥ 10 terminal villi in 10 fields at 10× magnification in each of 3 areas (slides). Red blood cells can be seen in many of the capillaries. Capillary proliferation can be seen in numerous terminal villi.

Figure 7

Figure 7. A 10× photomicrograph of a placenta from a woman who delivered a control patient. Chorangiosis is not present in this photmicrograph.