Date Published: March 22, 2019
Publisher: Oxford University Press
Author(s): Sarah J Kotecha, W John Watkins, John Lowe, Raquel Granell, A John Henderson, Sailesh Kotecha.
Although respiratory symptoms, including wheezing, are common in preterm-born subjects, the natural history of the wheezing phenotypes and the influence of early-life factors and characteristics on phenotypes are unclear. Participants from the Millennium Cohort Study who were born between 2000 and 2002 were studied at 9 months and at 3, 5, 7, and 11 years. We used data-driven methods to define wheezing phenotypes in preterm-born children and investigated whether the association of early-life factors and characteristics with wheezing phenotypes was similar between preterm- and term-born children. A total of 1,049/1,502 (70%) preterm-born children and 12,307/17,063 (72%) term-born children had recent wheeze data for 3 or 4 time points. Recent wheeze was more common at all time points in the preterm-born group than in term-born group. Four wheezing phenotypes were defined for both groups: no/infrequent, early, persistent, and late. Early-life factors and characteristics, especially antenatal maternal smoking, atopy, and male sex, were associated with increased rates for all phenotypes in both groups, and breastfeeding was protective in both groups, except late wheeze in the preterm group. Preterm-born children had similar phenotypes to term-born children. Although early-life factors and characteristics were similarly associated with the wheezing phenotypes in both groups, the preterm-born group had higher rates of early and persistent wheeze. However, a large proportion of preterm-born children had early wheeze that resolved with time.
From a total of 19,244 families, data were available from 18,552 (96.4%), 15,590 (81.0%), 15,246 (79.2%), 13,857 (72.0%), and 13,287 (69%) families at 9 months and 3, 5, 7, and 11 years, respectively. From 19,517 children in the original cohort, 18,565 (95.1%) had data on gestational age; 1,502 (8.1%) children were born preterm, of whom 1,049 (69.8%) had recent-wheeze data for at least 3 time points and thus were included in the phenotype analyses. From 17,063 term-born children, data for phenotype analyses were available for 12,307 (72.1%). Web Table 1 compares included and excluded children (results are discussed in Web Appendix 2), and Table 1 compares included preterm- and term-born children. Included preterm-born children had lower birth weight and gestational age, were less likely to be breastfed, and had fewer siblings and lower rates of formal childcare than included term-born children. However, they had higher rates of IUGR, cesarean delivery, neonatal unit admissions, hospital stays, asthma diagnosis, and antenatal maternal smoking, and the body mass index of a larger percentage of mothers of preterm-born children was outside the normal range, compared with mothers of term-born children. Socioeconomic status was similar.
Table 1.Demographic Characteristics of Preterm-Born and Term-Born Children, Born During 2000–2002, Who Had Wheezing Phenotype Data, Millennium Cohort Study, United KingdomCharacteristicPreterm Born (n = 1,049)Term Born (n = 12,307)P ValueNo.%Mean (SD)No.%Mean (SD)Mean birth weight, kga2.33 (0.68)3.43 (0.51)0.00Mean birth-weight z score0.01 (1.20)−0.03 (1.00)0.18Mean gestation, weeksa34.3 (2.4)39.8 (1.3)0.00 24–28 weeks’ gestation504.8 24–32 weeks’ gestation19218.3Male sex53651.16,20250.40.66IUGR at birtha,b,c14513.81,23810.10.00Antenatal maternal smokinga,b,d40839.03,98032.40.00Antenatal maternal smoking, no. of cigarettes per daya,b,d0.00 063961.08,31167.6 1–910610.11,0418.5 10–1917116.31,72514.0 ≥2013112.51,2149.9Socioeconomic statusb,e0.81 Management/professional29931.63,65532.9 Intermediate17818.82,14819.3 Self-employed384.04644.2 Supervisory/technical555.86636.0 Semiroutine/routine37539.74,17937.6Breastfeda,b,f68865.68,49369.00.02White ethnicityb,g88184.110,41684.80.53Cesarean deliverya,b,h45843.72,51620.50.00Admitted to neonatal unita,b,i54151.67105.80.00Length of stay after birth, daysa17.6 (24.3)3.1 (5.8)0.00Exposure to smoking after birth31730.23,43627.90.11Atopy at any age62359.47,37759.90.73Asthma diagnosisa33932.32,96924.10.00Maternal age at child’s birth, years29.1 (6.1)28.8 (5.8)0.16Maternal history of atopy0.13 Missing10.090.0 Asthma and eczema737.06975.7 Asthma or eczema24323.22,71622.1 None73269.88,88572.2Maternal prepregnancy BMIj23.8 (5.2)23.8 (4.4)0.86Maternal prepregnancy BMI categorya0.00 Refusal00.020.0 Not available918.79607.8 Underweight747.15934.8 Normal weight61358.47,39660.1 Overweight16515.72,36819.2 Obese928.89067.4 Morbidly obese141.3820.7Damp or condensation exposureb,k12612.01,65413.50.18Pollution, grime, and environmental problemsb,l0.51 Very common706.77496.1 Fairly common15014.51,94315.9 Not very common40338.34,77339.2 Not at all common41540.04,71838.7Number of siblings in householda0.86 (1.1)0.93 (1.0)0.03Childcarea,b,m0.00 Formal13512.91,75814.3 Informal28427.23,88231.6Abbreviation: BMI, body mass index; IUGR, intrauterine growth restriction; SD, standard deviation.aP < 0.05 between the term and preterm children with wheezing phenotype data.b Data was missing for some of the variables.c The total number of preterm children with data was 1,048. The total number of term children with data was 12,300.d The total number of preterm children with data was 1,047. The total number of term children with data was 12,291.e The total number of preterm children with data was 945. The total number of term children with data was 11,109.f The total number of term children with data was 12,306.g The total number of preterm children with data was 1,048. The total number of term children with data was 12,284.h The total number of preterm children with data was 1,048. The total number of term children with data was 12,252.i The total number of preterm children with data was 1,048.j Weight (kg)/height(m)2.k The total number of term children with data was 12,285.l The total number of preterm children with data was 1,038. The total number of term children with data was 12,183.m The total number of preterm children with data was 1,043. The total number of term children with data was 12,183. Using a well-established cohort with longitudinal data, we noted that rates of recent wheeze in preterm-born children, when compared with term-born children, were higher at each time point (although the association was weaker at 11 years), as previously reported (8, 32). We also defined 4 wheezing phenotypes as recently reported in largely term-born children in the MCS (33). The odds ratios for early and persistent wheeze were greater in the preterm group, but late wheeze was similar in both groups. Early-life factors and characteristics, especially antenatal maternal smoking, atopy, and male sex, were associated with wheezing phenotypes in both preterm and term groups, and breastfeeding was associated with decreased rates of wheezing phenotypes in both groups, except for late wheeze in the preterm-born children, although the magnitude of association according to various early-life factors and characteristics varied between the groups. However, prematurity was associated with higher rates of wheezing in the early and persistent groups but not the late-wheeze group, suggesting that delivery at an early stage of lung development is a risk factor for the development of certain wheezing phenotypes. Source: http://doi.org/10.1093/aje/kwy268