Suvi Alenius

People born preterm have reduced BMD, subnormal peak bone mass, and an increased risk of osteoporosis. Whether this translates to increased risk of bone fractures is uncertain. We assessed fracture risk from childhood to early adulthood in relation to gestational age and sex by conducting a nationwide register-linkage cohort study comprising all 223 615 liveborn (January 1987–September 1990) singletons (9161, 4.1%; preterm) in Finland. Cox regression models provided hazard ratios (HRs) for fracture diagnosis in public specialty health care in both first and recurrent event settings during the whole follow-up (0–29 years) and during different age periods (0–4, 5–9, 10–29 years). Gestational age was considered categorical (full-term, 39–41 weeks; reference). A total of 39 223 (17.5%) children or young adults had at least 1 fracture. In analyses not stratified by sex, only extremely preterm birth (<28 completed weeks’ gestation) was associated with risk of bone fracture at 0–29 years (adjusted HR [aHR]: 0.46; 95% CI: 0.28–0.74) compared with those born full-term. Among females, gestational age was unrelated to fracture risk at 0–29 years. Among males, extremely and very preterm (28–31 weeks) birth was associated with lower risk of fracture at 0–29 years compared with those born full-term (aHR: 0.38 [95% CI: 0.21–0.71] and 0.75 [95% CI: 0.59–0.95], respectively). Restricting the analyses to the individuals without severe medical condition(s) attenuated the associations. However, the fracture risk varied according age and sex: at 10–29 years, moderately preterm (32–33 weeks) females and extremely and very preterm males had a lower risk (aHR: 0.63 [0.43–0.94], 0.35 [0.17–0.69], and 0.74 [0.57–0.95], respectively), while late-preterm birth (34–36 weeks) was associated with a 1.6-fold higher risk among females at 0–5 years, and a 1.4-fold risk among males at 5–10 years. Analyses on recurrent fractures showed a similar pattern. Children and young adults, in particular males, born extremely or very preterm may have fewer bone fractures; this is partly explained by severe medical conditions in this group.

Aims/hypothesis: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23–27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. Methods: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23–27 completed weeks), very preterm (28–31 weeks), moderately preterm (32–33 weeks), late preterm (34–36 weeks), early term (37–38 weeks), full term (39–41 weeks; reference) and post term (42–45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. Results: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. Conclusions/interpretation: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term. Graphical

Background: Preterm birth affects lungs in several ways but few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease (COPD)) at age 18–50 years.Methods: We used nationwide registry data on 706 717 people born 1987–1998 in Finland (4.8% preterm) and 1 669 528 born 1967–1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland for 2005–2016 and in Norway for 2008–2017. We used logistic regression to estimate odds ratios (ORs) for having a care episode with either disease outcome.Results: Odds of any obstructive airway disease in adulthood for those born at <28 or 28–31 completed weeks were 2–3-fold of those born full term (39–41 completed weeks), persisting after adjustments. For individuals born at 32–33, 34–36 or 37–38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18–29 and 30–50 years. For COPD at age 30–50 years, the OR was 7.44 (95% CI 3.49–15.85) for those born at <28 weeks, 3.18 (95% CI 2.23–4.54) for those born at 28–31 weeks and 2.32 (95% CI 1.72–3.12) for those born at 32–33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born at <28 and 28–31 weeks.Conclusion: Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD call for diagnostic vigilance when adults born very preterm present with respiratory symptoms.

Attendance in special education (SE) is more common among individuals born preterm than among those born at term. Less is known about school grades of those born preterm in mainstream education (ME), and how these grades predict later educational attainment. This population-based register-linkage study assessed (1) attendance in SE, and then focused on those in ME by assessing (2) school grades at 16 year, (3) completed educational level at 25 year, and (4) school grades as predictors for completed education by gestational age (GA) with full-term birth (39–41 completed weeks) as reference. The sample comprised 223,744 individuals (10,521 preterm, 4.7%) born in Finland (1/1987–9/1990). Of the sample, 4.9% attended SE. Those born preterm had up to 5.5-fold rates for SE. In ME, those born extremely preterm (EPT) had marginally lower mathematics grades compared with full-term counterparts, whilst those born late preterm or early term had slightly higher grades. Those born EPT or very preterm had lower physical education grades in ME. However, the minor differences in school grades according to GA appear not to translate into educational differences in young adulthood. The associations between school grades at 16 year and completed education at 25 year did not vary by GA.

Background Preterm born young adults have elevated risks of individual respiratory, neuropsychiatric and cardiovascular diseases. However, the risk of chronic disease multimorbidity (the co-occurrence of ≥2 chronic, non-communicable diseases in one person) in preterm born individuals is unclear. We examined the risks of chronic disease multimorbidity (overall and specific disease combinations) in adolescence and early adulthood among people born across the spectrum of gestational ages. Methods We used individual-level data from nationwide birth, healthcare and population registers to examine the associations of gestational age at birth (ranging from 23 to 42+ completed weeks, with full-term, 39–40 weeks as the reference category) with multimorbidity (specialised healthcare records of ≥2 chronic diseases) in adolescence (age 10–17 years) and early adulthood (age 18–30 years). The study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1^stJanuary 1987 and 31^st December 2006, inclusive. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the multimorbidity outcomes using flexible parametric survival models, with adjustment for birthweight z-score, multiple pregnancy, congenital malformations and mother’s characteristics (age, parity, socioeconomic position, smoking, diabetes and hypertension during pregnancy). Results During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years) and during 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). We found a consistent dose-response relationship between earlier gestational age and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37–38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23–27 weeks (extremely preterm), independently of covariates. Among females, these risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37–38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23–27 weeks. The risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36–37 weeks but up to 3-fold risks observed among those born at 23–27 weeks (extremely preterm). Discussion Our findings indicate that preterm born adolescents and young adults have increased risks of chronic disease multimorbidity, with the risks increasing consistently with increasing degree of prematurity.There are currently no clinical guidelines for following up preterm-born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescents and young adults.

Background: People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. Methods and findings: We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10–17 years) and early adulthood (age 18–30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1^st January 1987 and 31^st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37–38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23–27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37–38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23–27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36–37 weeks but up to 3-fold risks observed among those born at 23–27 weeks. Conclusions: Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients.

Background: Preterm birth predisposes to child protection action in the form out‐of‐home care. The impact of the degree of preterm birth on the likelihood for OHC placement(s) and their timing is unknown.Methods: This population‐based register‐linkage study assessed the likelihood of OHC placement in different gestational age groups using multivariable Cox regression models. All 193 033 traceable singleton (8324 preterm, 4.3%) liveborn in Finland (January 1987‐September 1990), as the first index child of each mother within the cohort period, were followed up until their 18th birthday.Results: A total of 6562 children (3.4%) experienced OHC. In comparison with full‐term children (39‐41 weeks), those born at 23‐33 completed weeks were predisposed to OHC (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.74, 2.56). For those born late preterm (34‐36 weeks) and early term (37‐38 weeks), the HR were 1.54 (95% CI 1.37, 1.73) and 1.19 (95% CI 1.12, 1.26), respectively. Adjustment for parental and child characteristics attenuated the HRs: 23‐33 weeks: 1.31 (95% CI 1.07, 1.59), 34‐36 weeks: 1.17 (95% CI 1.04, 1.31), and 37‐38 weeks: 1.08 (95% CI 1.02, 1.16). However, the adjusted HRs for first OHC entries at 0‐5 years of age were higher: 23‐33 weeks 2.29 (95% CI 1.72, 3.05), 34‐36 weeks 1.76 (95% CI 1.46, 2.13), and 37‐38 weeks 1.40 (95% CI 1.25, 1.56). Among those born preterm or early term, in comparison with their term born peers, no excess risk for OHC was seen after 5 years.Conclusions: A dose‐response relationship exists between the level of preterm birth and OHC placement risk. OHC placements are more common among early and late preterm, and early term children, compared with those born full term, and occur at younger age. Perinatal and postnatal adverse circumstances appear to explain the phenomenon only partly.

BACKGROUND: Parents of very or extremely low birth weight infants have fewer subsequent children after preterm birth. Whether this applies to parents of less preterm infants is unknown.METHODS: In this nationwide cohort study, we identified all 230 308 traceable (>99%) singletons (9983 preterm, 4.3%) live born in Finland between January 1, 1987, and September 30, 1990, and their parents. Quantitative contribution of gestational age of child to the birth of parental subsequent children was assessed by multivariate Cox regression models, stratifying by the number of previous children. The impact of gestational age on sibling count was estimated at individual and population level.RESULTS: Mothers of extremely preterm (23–27 completed weeks) infants were, compared with mothers of term infants (39–41 weeks), less likely to have a subsequent live-born child (adjusted hazard ratio [HR]: 0.74; 95% confidence interval: 0.63–0.86). Corresponding HRs and confidence intervals were as follows: 28 to 31 weeks: 0.72 (0.65–0.80), 32 to 33 weeks: 0.82 (0.74–0.90), and 34 to 36 weeks: 0.90 (0.87–0.93). These HRs were consistent with those of fathers and couples. The cohort included 8002 firstborn preterm children, of whom 356 (4.4%) died in infancy. The 8002 children had a total of 13 826 subsequent siblings (1138 less than expected); per 1000 preterm births, this translates to the death of 44 preterm infants and 142 missing subsequent siblings.CONCLUSIONS: Families with a preterm singleton child have fewer subsequent children. In a high-income country, the main population effect of preterm birth is caused by these “missing siblings,” whose number exceeds the number of those preterm infants who die.