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Born Small for Gestational Age: Beyond Size at Birth
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk obstetrik)ORCID iD: 0000-0003-4427-1075
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Children born small for gestational age (SGA) run increased risk of perinatal morbidity and mortality, but also of long-term health impairment. Risks on long term may vary depending on postnatal growth patterns. The overall aim of the thesis was to gain further knowledge about long-term consequences of being born SGA, as well as the impact of perinatal exposures on postnatal growth patterns. The thesis is based on four register-based cohort studies.

In paper I, risk of chronic hypertension was assessed in 731,008 first-time mothers. Perinatal exposure to pre-eclampsia, being born SGA and preterm were all independently associated with increased risk of chronic hypertension. The risk was further enhanced after combined exposure. The strongest association was seen in combinations including pre-eclampsia.

In paper II, risk of poor school performance at time of graduation from compulsory school was assessed in 1,088,980 children born SGA at term. Being born SGA was associated with increased risk of poor school performance, following a dose-response pattern with increased risk even for birthweight for gestational age (GA) –1.01 to –2 SD. Boys with short adult stature were associated with higher risk of poor school performance than those with non-short stature.

In paper III, differences in postnatal growth patterns depending on SGA status and maternal smoking habits were assessed in 32,493 children. Children born SGA with smoking mothers had a more rapid catch-up growth than those with non-smoking mothers. Compared with children born appropriate for GA (AGA) with non-smoking mothers, only children born SGA with non-smoking mothers were associated with increased risk of short stature at 1.5 and 5 years.

In paper IV, differences in postnatal growth patterns until age five years, depending on SGA status and GA at birth, were assessed in 41,669 children born between 32-40 gestational weeks. Being born SGA and moderate to late preterm was associated with shorter stature and lower BMI, compared with being born AGA at term. SGA status had greater impact on growth and body proportions than GA at birth.

In conclusion, children born SGA are at higher risk of chronic hypertension and cognitive impairment than children born AGA. Postnatal growth patterns vary in children born SGA, depending on intrauterine exposure to smoking and GA at birth. This may modify risks of long-term health impairment.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 89
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1543
Keywords [en]
Small for Gestational Age, SGA, Epidemiology, Pregnancy, Postnatal growth, Intrauterine growth restriction, Chronic hypertension, School performance
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-374782ISBN: 978-91-513-0581-3 (print)OAI: oai:DiVA.org:uu-374782DiVA, id: diva2:1290575
Public defence
2019-04-12, Humanistiska teatern, Engelska parken, Thunbergsv. 3H, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2019-03-21 Created: 2019-02-20 Last updated: 2019-05-07
List of papers
1. Chronic hypertension in women after perinatal exposure to preeclampsia, being born small for gestational age or preterm
Open this publication in new window or tab >>Chronic hypertension in women after perinatal exposure to preeclampsia, being born small for gestational age or preterm
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2017 (English)In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 31, no 2, p. 89-98Article in journal (Refereed) Published
Abstract [en]

Background: There is an established association between adverse events during perinatal life and chronic hypertension in adult life. However, disadvantageous conditions often coexist in the same pregnancy. We investigated single and joint perinatal exposure to preeclampsia, being born small for gestational age (SGA) or preterm and subsequent risk of chronic hypertension.

 

Methods: The study population consisted of 731,008 primiparous women from Norway and Sweden registered in the Medical Birth Registers, both as infants and as first time mothers between 1967-2009 (Norway) and 1973-2010 (Sweden). Risk of chronic hypertension in early pregnancy was calculated in women perinatally exposed to preeclampsia, born SGA or preterm by log-binominal regression analysis, and adjusted for maternal age and level of education in the 1st generation.

 

Results: The rate of chronic hypertension was 0.4%. Risk of chronic hypertension was associated with single perinatal exposure to preeclampsia, being born SGA or preterm with adjusted relative risks (95% confidence intervals, CI) 2.2 (95% CI 1.8, 2.7), 1.1 (95% CI 1.0, 1.3) and 1.3 (95% CI 1.0, 1.5) respectively. The risks increased after joint exposures, with an almost 4-fold risk increase after perinatal exposure to preeclampsia and preterm birth. Additional adjustment for BMI and smoking in the 2nd generation in a subset of the cohort only had a minor impact on the results.

 

Conclusions: Perinatal exposure to preeclampsia, being born SGA or preterm is independently associated with increased risk of chronic hypertension. The highest risk was seen after exposure to preeclampsia, especially if combined with SGA or preterm birth.

Keywords
chronic hypertension, preeclampsia, preterm birth, small for gestational age
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-319182 (URN)10.1111/ppe.12346 (DOI)000395008000001 ()28218407 (PubMedID)
Funder
Swedish Research Council, 2014-3561The Karolinska Institutet's Research Foundation
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2019-02-20Bibliographically approved
2. Born Small for Gestational Age and Poor School Performance: How Small Is Too Small?
Open this publication in new window or tab >>Born Small for Gestational Age and Poor School Performance: How Small Is Too Small?
2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, p. 215-223Article in journal (Refereed) Published
Abstract [en]

Aim: To assess the relationship between severity of small for gestational age (SGA) and risk of poor school performance, and to investigate whether adult stature modifies this risk.

Methods: 1,088,980 term Swedish children born 1973-1988 were categorized into severe SGA (<-3 standard deviations (SD) of expected birth weight), moderate SGA (-2.01 to -3 SD), mild SGA (-1.01 to -2 SD) and appropriate for gestational age (-1 to 0.99 SD). Risk of poor school performance at time of graduating from compulsory school (grades <10th percentile) was calculated using unconditional logistic regression models and adjusted for socioeconomic factors. In a sub-analysis, we stratified boys by adult stature, and adjusted for maternal but not paternal height.

Results: All SGA groups were significantly associated with increased risk of poor school performance, with adjusted odds ratios (aOR) and 95% confidence intervals (CI) ranging from 1.85 (1.65-2.07) for severe SGA to 1.25 (1.22-1.28) for mild SGA. In the sub-analysis, all birth weight groups were associated with increased risk of poor school performance among boys with short staturecompared with non-short stature.

Conclusion: Mild SGA is associated with significantly increased risk of poor school performance, and the risk increases with severity of SGA. Further, this risk diminishes after adequate catch-up growth.

Keywords
Small for gestational age, intrauterine growth, cognitive development, catch-up growth, stature
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-330118 (URN)10.1159/000477905 (DOI)000415251200005 ()28697501 (PubMedID)
Projects
Perspectives on Intrauterine Growth and Perinatal Exposure
Funder
Swedish Research Council, 2014-3561
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2019-02-20Bibliographically approved
3. Postnatal growth in children born small for gestational age with and without smoking mother
Open this publication in new window or tab >>Postnatal growth in children born small for gestational age with and without smoking mother
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2019 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 85, no 7, p. 961-966Article in journal (Refereed) Published
Abstract [en]

Background: Maternal smoking impairs fetal growth; however, if postnatal growth differs between children born small for gestational age (SGA) with smoking and non-smoking mother is unknown.

Methods: Cohort-study of term born children born appropriate for gestational age with non-smoking mother (AGA-NS, n=30,561), SGA (birthweight <10th percentile) with smoking mother (SGA-S, n=171) or SGA with non-smoking mother (SGA-NS, n=1761). Means of height and weight measurements, collected at birth, 1.5, 3, 4 and 5 years, were compared using a generalized linear mixed effect model. Relative risks of short stature (<10th percentile) were expressed as adjusted risk ratios (aRR).

Results: At birth, children born SGA-S were shorter than SGA-NS, but they did not differ in weight. At 1.5 years, SGA-S had reached the same height as SGA-NS. At 5 years, SGA-S were 1.1 cm taller and 1.2 kg heavier than SGA-NS. Compared with AGA-NS, SGA-S did not have increased risk of short stature at 1.5 or 5 years, while SGA-NS had increased risk of short stature at both ages; aRRs 3.0 (95% CI 2.6;3.4) and 2.3 (95% CI 2.0;2.7), respectively.

Conclusions: Children born SGA-S have a more rapid catch-up growth than SGA-NS. This may have consequences for metabolic and cardiovascular health in children with smoking mothers.

National Category
Obstetrics, Gynecology and Reproductive Medicine Pediatrics
Identifiers
urn:nbn:se:uu:diva-374779 (URN)10.1038/s41390-019-0352-5 (DOI)000468524800013 ()30808020 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-09-05Bibliographically approved
4. Born small for gestational age and moderate preterm; implications on postnatal growth
Open this publication in new window or tab >>Born small for gestational age and moderate preterm; implications on postnatal growth
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(English)In: Article in journal (Refereed) Submitted
Abstract [en]

Today we lack knowledge if size at birth and gestational age interacts regarding postnatal growth pattern in children born at 32 gestational weeks or later.

This population-based cohort study comprised 41,669 children born in gestational weeks 32-40 in Uppsala County, Sweden, between 2000 and 2015. We applied a generalized least squares model including anthropometric measurements at 1.5, 3, 4 and 5 years. We calculated estimated mean height, weight and BMI for children born in week 32+0, 35+0 or 40+0 with birthweight 50th percentile (standardized appropriate for gestational age, sAGA) or 3rd percentile (standardized small for gestational age, sSGA).

Compared with children born sAGA at gestational week 40+0, those born sAGA week 32+0 or 35+0 had comparable estimated mean height, weight and BMI after 3 years of age. Making the same comparison, those born sSGA week 32+0 or 35+0 were shorter and lighter with lower estimated mean BMI throughout the whole follow-up period.

Our findings suggest that being born SGA and moderate preterm is associated with short stature and low BMI during the first five years of life. The association seemed stronger the shorter gestational age at birth.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-374781 (URN)
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-02-20

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