Adults Born Preterm

Abstract

Background

Advances in neonatology now enable increasing numbers of very low birth weight neonates (R<1500 g) to survive into early adulthood and beyond. What are the implications for their long-term care?

Methods

Selective literature search on the outcome of very low birth weight neonates in adulthood (“adults born preterm”).

Results

Robust data are available on the pulmonary, metabolic, cardiovascular, renal, neurocognitive, sensory-visual, social-emotional, mental, reproductive, and musculoskeletal long-term risks. On the somatic level, elevated rates have been documented for asthma (odds Ratio [OR] 2.37), diabetes mellitus (OR 1.54), and chronic renal disease (hazard ratio [HR] 3.01), along with the cardiovascular and cerebrovascular sequelae of a tendency toward arterial hypertension. On the psychosocial level, the main findings are deficits in romantic partnerships (OR 0.72) and a lower reproduction rate (relative risk [RR] male/female 0.24/0.33). The affected women also have an elevated risk of preterm delivery.

Conclusion

A risk profile with both somatic and psychosocial aspects can be discerned for adults who were born prematurely, even if some of these risks are present in low absolute numbers. As the ability to compensate for latent deficits declines with age, such adults may suffer from “premature aging as the late price of premature birth.” A holistic approach to care with personalized prevention strategies—which for most of them was discontinued at discharge from pediatric follow-up—therefore seems appropriate in adulthood as well.

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de. The deadline for submissions is 8 August 2022.

Thanks to advances in neonatology, the mortality rate in preterm infants has continuously declined in recent years. Even in preterm infants born in the 23^rd–24^th gestational week (GW), that is to say, at the border of viability, one can expect a survival rate of 60–80%; having said that, between a quarter and a third of surviving neonates suffer immediate neurological sequelae (1, 2, e1– e4).

These patients are only the most striking representatives of the large group of infants born prematurely, that is, before the completed 37^th week of gestation—a group that accounts for approximately 10% of all births worldwide. In turn, around 10% of these are born with a birth weight < 1500 g, corresponding to a gestational age of < 30 GW, and are referred to as “very low birth weight infants” (VLBWI) (3, e5, e6).

In the short and medium term, the majority of preterm infants can lead a full or largely unimpaired life. However, irrespective of organic disabilities, which are mostly diagnosed at an early age, other functional deficits sometimes occur that typically do not become apparent until an age is reached at which corresponding skills are required (2, e7). There is no cut-off value for behavioral disorders and learning disabilities of this kind, which represent a burden on families that should not be underestimated. Indeed, it is far more the case that special educational needs, for example, increase from the 37^th GW downwards with each week of prematurity, reaching a rate of 50–60% among the smallest preterm infants (4). Here, the causes of preterm birth, in addition to the degree of prematurity, determine the prognosis: whereas perinatal infections, for example, increase the risk of neurological sequelae, intrauterine growth restriction may promote later metabolic syndrome through what is referred to as fetal programming (5).

Although neonatal intensive care had already been introduced in the 1960s, it was initially doomed to fail in many cases primarily due to the newborn respiratory distress syndrome that occurs before the 30^th GW. It was not until the introduction of surfactant replacement therapy to treat fetal lung immaturity in the 1980s that the treatment of very low birth weight infants succeeded—and has been continuously perfected ever since (e8, e9). As a result, a growing number of people belonging to this group will reach medium to advanced age in the coming years.

Many of these patients will have undergone pediatric follow-up ending at the latest in adolescence and, thus, in a phase of life at which most have achieved, at least subjectively, a satisfactory quality of life (6, e10, e11). When they seek medical advice again for new health problems as they grow older, they will introduce their former preterm birth into the conversation with degrees of importance that vary from individual to individual. The primary care physicians or specialists being consulted will then ask themselves what objective significance the history of preterm birth could have for their now adult patients—as well as in terms of the possible impact on their ongoing care.

Methods

In order to help answer this question, we selected in a targeted manner articles with the term “adults born preterm” that addressed the long-term outcome (> 20 years) of very low birth weight infants (< 1500 g). The most robust data can be found in meta-analyses and birth registry studies, which are particularly common in Scandinavian countries. Although relative increases in risk are usually argued here, the statistical significance of which sometimes contrasts to some extent with the low absolute incidences and prevalences, a relevant risk profile can be discerned from these studies and can be subdivided into 10 somatic and psychosocial categories.

Pulmonary risk

Even after surfactant therapy for respiratory distress syndrome and despite ever less invasive ventilation, a highly variable percentage (10–70%) of very low birth weight infants develop primarily inflammation-mediated and likely genetically underpinned bronchopulmonary dysplasia (BPD) (e12, e13). Although the cardinal symptom, a persistently elevated oxygen requirement, usually resolves with age, a 15–20 percentage point reduction in forced expiratory volume in 1 s (% FEV₁), as evidenced by an extensive meta-analysis (7), remains following BPD (table 1) and can progress to (manifest) chronic obstructive pulmonary disease (COPD) (8, 9, e14). As early on as in young adulthood, some former very low birth weight infants exhibited severe asthma in a Norwegian study (10), at a prevalence of 1.5–2.5% compared to approximately 0.5% in full-term newborns (adjusted OR 2.4) (table 1).

Table 1. Pulmonary risk in adults born preterm*.

Source	Country/Baseline population	Study population	Long-term sequelae	Relative risks, adjusted [95% CI]	Incidences/prevalences, relative and absolute
(7)	Meta-analysis n = 2085 (59 studies)	1984–2010 (Publication years) < 37 gw	% FEV1 All – BPD + BPD28 + BPD36	–8.70% [–10.98; –6.42] –7.15% [–8.73; –5.58] –16.16% [–19.90; –12.42] –18.92% [–21.14; –16.70]	Versus FTN (n = 3820)
(10)	Norway n = 1 760 821	1967–2001 (→ 2005) 23–31 GW	Asthma	OR 2.37 (2.01; 2.79)	Ca. 2.0 versus 0.5% (FTN) Ca. 190 of 9512

*Here using the example of % FEV1 (forced expiratory volume in 1 s) and asthma. This table and Tables 2– 5 list the studies and meta-analyses specifically mentioned in the text regarding the long-term risks of preterm birth (weeks of gestation [GW], observation period [→], life years [LY]). In addition to the relative risks (odds ratio [OR]; hazard ratio [HR]; relative risk [RR]; confidence interval [CI]), the associated incidences and prevalences (person-years [PY]), where available, are given in percentages and absolute numbers compared to the respective reference population (baseline population [BP], full-term neonates [FTN], study control group [CG]). In the case of meta-analyses, the number of preterm infants included is listed in the “Baseline population” column, while the number of individuals in the comparison collective is listed in the “Incidences/prevalence” column. In the meta-analysis on forced expiratory volume in 1 s, the difference in FEV₁ percent was recorded in former preterm infants with/without bronchopulmonary dyplasia (±BPD), defined as persistent oxygen requirement at 28 days of life (BPD₂₈) or 36 postmenstrual weeks (BPD₃₆).

Metabolic risk

Based on the observation that patients with coronary heart disease often had low birth weights, Barker (11) arrived at his ground-breaking hypothesis on the intrauterine origin of metabolic syndrome. It would appear that the growth-retarded fetus is programmed for a “thrifty” metabolism to such an extent that even a normal substrate intake can have the effect of an excessive intake in later life and, through obesity, hyperglycemia, and hyperlipoproteinemia, lead to atherosclerosis and its sequelae (12, e15, e16). For example, in a Finnish study (13), former very low birth weight infants already exhibited at 18–27 years a 6.7% higher 2-h blood glucose (95% confidence interval [CI]: [0.8; 12.9]) despite a 40.0% (CI: [17.5; 66.8]) higher insulin level compared to full-term infants. Latent insulin resistance is a precursor of manifest diabetes mellitus. Although it was rare overall in a Swedish VLBWI collective (14) aged 26–37 years, diabetes was seen to develop (with an adjusted odds ratio of 1.5) significantly more frequently (table 2).

Table 2. Metabolic, cardiovascular, and renal (cardiometabolic) risks in adults born preterm*.

Source	Country/Baseline population	Study population	Long-term sequelae	Relative risks, adjusted [95% CI]	Incidences/prevalences, relative and absolute
(14)	Sweden n = 630 090	1973–79 (→ 2005–09) 23–28 GW 29–34 GW	Diabetes mellitus	OR 1.54 [0.76; 3.15] OR 1.09 [0.90; 1.32]	1.9 vs. 1.2% (FTN) 8 of 419 1.4 vs. 1.2% (FTN) 117 of 8509
(15)	Meta-analysis n = 1571 (9 studies)	1977–93 (birth cohorts) < 1500 g	Arterial Systolic hypertension Diastolic	+ 3.4 mm Hg [2.2; 4.6] + 2.1 mm Hg [1.3; 3.0]	vs. FTN (n = 777)
(17)	Sweden n = 2 141 709	1973–94 (→ 18–43 LY) < 34 gw < 37 gw	Coronary 18–43 LY heart disease 30–43 LY 18–43 LY 30–43 LY	HR 0.93 [0.58; 1.51] HR 1.22 [0.69; 2.16] HR 1.44 [1.19; 1.73] HR 1.53 [1.20; 1.94]	5.7 vs. 5.9 x 10–5 PY (FTN) 17 of 21 748 15.3 vs.11.9 x 10–5 PY (FTN) 12 of 21 748 8.8 vs. 5.9 x 10–5 PY (FTN) 126 von 101 988 19.0 vs. 11.9 x 10–5 PY (FTN) 74 von 101 988
(20)	Sweden n = 4 186 615	1973–2014 (→ 43 LY) 22–27 GW 28–33 GW	Chronic kidney disease	HR 3.01 [1.67; 5.45] HR 2.22 [1.79; 2.75]	13.3 vs. 4.5 x 10–5 PY (FTN) 11 of 8129 10.7 vs. 4.5 x 10–5 PY (FTN) 87 of 43 516

*Here using the example of diabetes mellitus, propensity to arterial hypertension, coronary heart disease, and chronic kidney disease. In the Swedish study on coronary heart disease, the increase in risk was even more marked if the subgroup of already somewhat older subjects (30–43 LY) was considered separately and if the less premature (late) preterm infants (< 37 GW) were included.

HR, hazard ratio; CI, confidence interval; LY, life years; OR, odds ratio; PY, person years; FTN, full-term neonate; GW, gestational weeks; vs.,versus; →, observation period

Cardiovascular risk

According to a large meta-analysis (15), former very low birth weight infants exhibit systolic/diastolic arterial blood pressure that is on average 3.4/2.1 mm Hg higher, representing a further risk factor for cardiometabolic diseases (table 2). The propensity to arterial hypertension given attention not so much for its severity as for its regular occurrence (12, 16, e17) is explained by, among other factors, the fact that the wall stiffness in the large arteries is increased and the capillary bed rarefied (e18). In addition, cardiac magnetic resonance imaging (MRI) demonstrated altered geometry of the left ventricular myocardium (e19). All these risk factors likely contribute to the (slightly) increased risk (adjusted HR 1.22) for coronary heart disease found in a Swedish study (17) on adults aged 30–43 years following preterm birth before the 34^th GW (table 2). This result corrected earlier statistics that had found no significant increase in risk (18), and was used by authors and editorialists to recommend cardiac prevention for the affected group of individuals (17, 19).

Renal risk

As is true for the lungs and the brain, it is also true for the kidneys that, following preterm birth, their maturation (nephrogenesis) takes place partially extrauterine—with possible consequences in terms of organ size and function (e20, e21). In addition, there appear to be close interactions with cardiovascular status (16), be it that the (unduly small) kidney contributes to arterial hypertension or that it is (additionally) damaged by metabolic and hemodynamic factors. In a large Swedish cohort study (20), former very low birth weight infants had an adjusted HR of 3.01 for chronic kidney disease in young adulthood (table 2). The incidence rose from 4.5 to 13 (per 100,000 patient-years), prompting the study authors to warn of a silent epidemic of chronic kidney disease in this patient group (21). This concern applies especially to young women with regard to possible transgenerational nephrogenic complications of pregnancy (22).

Neurocognitive risk

Neurological risks in adults born preterm include severe early-onset organic brain complications as well as less severe learning disabilities that come to light in the further course. In addition to this, and much like the cardiovascular risk, cerebrovascular diseases occur more frequently. A Swedish study (18) found an HR of 1.89 in this regard in former very low birth weight infants, corresponding to an increase in incidence to 0.13% compared to 0.07% in former full-term infants (table 3). In addition, MRI studies of former preterm infants identified structural abnormalities in individual areas of the brain that are presumably the result of (cerebral) brain development occurring under unnatural extrauterine environmental conditions. In neuropsychological tests, these correlated with abnormal cognitive and executive functions (e22– e24). Finally, the internal architecture of the brain also appears to be able to change in adaptation to existing sensory deficits (23).

Table 3. Neurological and sensory (visual) risks in adults born preterm*.

Source	Country/Baseline population	Study population	Long-term sequelae	Relative risks, adjusted [95% CI]	Incidences/prevalences, relative and absolute
(18)	Sweden n = 1 306 943	1983–95 (→ 15 LY to 2010) < 32 gw	Cerebrovascular diseases	HR 1.89 (1.01; 3.54)	0.13 vs. 0.07% (FTN) 10 of 7764
(24)	Sweden n = 3 423 697	1973–86/1987–2008 (→ 1 LY to 2009) < 28 gw 28–31 GW	Retinal detachment 1973–86 1987–2008 1973–86 1987–2008	HR 19.2 (10.3; 35.8) HR 8.95 (3.98; 20.1) HR 4.32 (2.70; 6.90) HR 2.80 (1.38; 5.69)	1.6 vs. 0.1% (FTN) 10 of 636 0.18 vs. 0.02% (FTN) 6 of 3328 0.34 vs. 0.1% (FTN) 18 of 4680 0.06 vs. 0.02% (FTN) 8 of 11 826

*Here using the example of cerebrovascular diseases and retinal detachment. The data on retinal detachment reflect the progress made between an observation period longer ago and one that is more recent; it is mainly patients in the older age cohorts that will more frequently seek medical advice in the coming years. HR, hazard ratio; CI, confidence interval; LY, life years; FTN, full-term neonate; GW, gestational week; vs.,versus; →, observation period

Sensory (visual) risk

These sensory deficits primarily include visual disturbances that largely result from the “retinopathy of prematurity” (ROP) typical at the ocular level in the smallest preterm infants, despite all the advances in prevention and treatment (e25). A cohort study of >3 million Swedish citizens (24) described an increased adjusted HR for retinal detachment in former preterm infants (<28 GW): before screening eye examinations were introduced in neonatology in 1987, it was 19.2, and subsequently still 8.95—at incidences of 1.6 and 0.18%, respectively, compared to 0.1 and 0.02%, respectively, in former full-term infants (table 3). In addition, there are also other visual impairments following preterm birth, for example, of visual acuity, convergence, and stereopsis, which—together with the disorders of central nervous visual processing recently observed more frequently—may be contributing, undetected, to presumed cognitive deficits (25, e26, e27).

Socio-emotional risk

At the intersection between neurosensory and mental health risks, one finds socio-emotional problems that, although in themselves without pathological significance in the narrower sense, can still be life-determining (e28). According to the groundbreaking research conducted by Wolke and coworkers, although most very low birth weight infants later develop “in an adaptive manner and within the normal range” (26), they tend—due to various minor performance deficits and significantly compounded by negative experiences with peers (bullying) (e29)—to be anxious, socially withdrawn, and more rarely achieve full occupational and financial independence. Also, with a pooled OR of 0.72, a remarkably high number of adults born prematurely did not experience a romantic partnership, as shown in an extensive meta-analysis (27, e30) of numerous cohort and registry studies (table 4). These and other abnormalities impair not only quality of life, but also contribute to the manifestation of mental illness (28).

Table 4. Socio-emotional, mental health, and reproductive risks in adults born preterm*.

Source	Country/Baseline population	Study population	Long-term sequelae	Relative risks, adjusted [95% CI]	Incidences/prevalences, relative and absolute
(27)	Meta-analysis n = 176 632 (14 studies)	≥ 18 LY < 37 gw, < 2500 g	Romantic partnership	OR 0.72 [0.64; 0.81]	vs. FTN (n = 4,190,857)
(30)	Meta-analysis n = 1426 (12 studies)	3.5–32 LY < 32 gw, < 1500 g	Attention deficit hyperactivity disorder	RR 3.04 [2.19; 4.21]	vs. FTN (n = 4737)
(32)	Norway n = 1 167 506	1967–76 (→ 2004) 22–27 GW 28–32 GW	Reproduction (parenthood)	RR 0.24 [0.17; 0.32] M RR 0.33 [0.26; 0.42] F RR 0.70 [0.66; 0.74] M RR 0.81 [0.78; 0.85] F	14 vs. 50% (FTN) M 30 of 216 25 vs. 68% (FTN) F 54 of 216 39 vs. 50% (FTN) M 747 of 1935 59 vs. 68% (FTN) F 913 of 1543

*Here using the example of having a romantic partnership, the incidence of attention deficit hyperactivity disorders, and the rate of fulfilled parenthood. CI, confidence interval; LY, life years; M, male; OR, odds ratio; FTN, full-term neonate; RR, relative risk; GW, gestational weeks; vs.,versus; F, female; →, observation period

Psychological risk

In extremely low birth weight infants (< 1000 g), internalizing problems fail to decline between the second and the fourth decade of life, as would be expected (29, e31), which is consistent with the depressive symptoms often complained of in self-help groups. The psychiatric diagnoses typical of preterm birth include—in addition to autism spectrum disorders, which are closely associated with the abovementioned socio-emotional abnormalities—attention deficit hyperactivity disorder (ADHD) (e32, e33). A recent meta-analysis (30) found a pooled relative risk for ADHD of 3.04 with a striking prevalence of 21.5% in the group of former very low birth weight infants (table 4). Eating disorders, which are well known from pediatric follow-up, have been little studied as yet—although recent data suggest they occur in up to 20% of former very low weight infants (31). Their progression to anorexia nervosa have already been noted in the past (e34).

Reproductive risk

With remarkable concordance, epidemiological studies conducted in several countries have found a lower reproductive rate in adults born preterm (32, e35, e36). In a Norwegian study (32) of extremely preterm women, only 25% had had children by the age of 28–37 years compared to 68% of women born full-term. This phenomenon depends on the degree of prematurity and affects males even more than females (table 4). Whether this can be attributed to somatic causes in addition to the abovementioned problems of partner selection (27) remains an unanswered question. In addition, former preterm women have an increased risk for experiencing preterm births themselves. This could be as a result of the fact that metabolic syndrome predisposes to diabetic or hypertensive complications of pregnancy (22, e37). According to a Canadian study, however, this phenomenon also appears to exist independently of epigenetic factors of this kind (33).

Musculoskeletal risk

Little is known about the long-term consequences of preterm birth on the musculoskeletal system. Since the introduction of osteopenia of prematurity prevention using adequate calcium, phosphate, and vitamin D supplementation, pathologic fractures have become rare on preterm intensive care units (e38). However, decreased bone density of the femoral neck has been repeatedly reported in former preterm infants, particularly after intrauterine growth restriction (e39– e41), thereby suggesting an increased risk for fractures in advanced age. In an Australian study (34), preterm birth (by ≥ 2 GW) was associated with an adjusted HR of 2.53 for hip arthroplasty at age ≥ 40 years, with incidences of 3.8% versus 2.1% in the baseline population (table 5). Finally, motor handicaps or physical inactivity may contribute to musculoskeletal symptoms in adults born preterm.

Table 5. Musculoskeletal risk in adults born preterm*.

Source	Country/Baseline population	Study population	Long-term sequelae	Relative risks, adjusted [95% CI]	Incidences/prevalences, relative and absolute
(34)	Australia n = 3604	Age ≥ 40 LY PB ≥ 2 GW	Hip arthroplasty	HR 2.53 [1.30; 4.92]	3.9 vs. 2.1% (BP) 11 of 279

*Here using the example of artificial hip replacement. PB, preterm birth; BP, baseline population; HR, hazard ratio; CI, confidence interval; LY, life years; GW, gestational weeks; vs.,versus

Discussion

The studies cited here are subject to three caveats: First, the majority of very low birth weight infants have only now reached middle adulthood, where health problems—measured in absolute numbers—are still minor, and a significant relative increase in risk could be due to a handful of patients with particularly unfavorable outcomes. As such, it is unclear whether the current risk profile will be substantiated or will level out in older age. Second, many of the oldest patients followed-up were born before the introduction of surfactant replacement therapy, at a time when neonatal intensive care was far more limited and, at the same time, more invasive than today. Therefore, this article on the current outcome of infants born preterm at that time should not be interpreted as a description of the—presumably and hopefully in many points more favorable— future prognosis of today’s preterm infants. Third, a number of questions that are equally of interest in this context, such as concerning cancer or dementia, cannot be answered as yet due to the lack of sufficient follow-up time.

Nevertheless, the available data make it possible to identify a risk profile that is characterized by a combination of somatic and psychosocial factors that varies in an age-dependent manner (5, 26): initially, neurocognitive deficits and problems of social integration appear to predominate, making occupational independence difficult and hindering successful family formation. Then, the predisposition to metabolic syndrome may promote the early onset of cardiovascular disease, while the reduced pulmonary reserve may bring patients to the limits of their respiratory capacity faster than is usual in the physiological aging process. Consistent with this, not all (e42, e43) but some recent molecular biological studies (35, e44) in adults born preterm have found shorter telomere length. Thus, premature aging may be the price that affected individuals pay later in life for preterm birth not only at the systemic level, but also at the cell biological level (8, 16, e14, e45).

The growing number of patients that reach adulthood at all thanks to advances in medicine is reminiscent of the transition problems known in rare (metabolic) diseases (36, e46)—with the difference that preterm birth is not only much more frequent compared to the rare diseases in question, but that most preterm infants are also not subject to seamless ongoing treatment. The result of this, however, is that when they subsequently seek medical advice once again, the continuity of their former preterm follow-up care has been discontinued and is sorely missed by at least some of the affected individuals (37, e47). There is an analogy to be made here to adults with congenital heart disease (ACHD) for whom so-called ACHD centers were set up, likewise around 30 years after the early days of pediatric cardiac surgery (38, e48)—again with the difference that in preterm infants it is less a matter of previously unknown organ complications and more one of a novel, perinatal risk profile.

To assess this risk profile, a differentiated medical history is first required, for which some key questions are listed in Table 6. It is generally true that not all preterm births are alike, and that possible subjective (mis-)attributions can be differentiated from objective risk constellations based only on the degree of prematurity and the causes of preterm birth. Whether specialist neonatology outpatient clinics for adults born preterm, much like the ACHD centers mentioned above, may be able to help with this differentiation in the future—at least in particularly complex cases—remains to be seen. If risks can be demonstrated, one can expect to see increased vulnerability to exogenous noxious agents (pulmonary function) (8– 10, e13, e14) or lifestyle factors (cardiometabolic risk) (e15, e16, e49). This in turn leads to consequences for personalized prevention (12, 19, 21, 39, 40, e50), which, in this case, must also take into account the special interrelationship between somatic and psychosocial factors. However, it is even more important to recognize that (extremely) preterm birth represents a chapter of life for those affected that can never be completely closed. Therefore, adults born preterm can benefit in particular from holistic, long-term, and, in the best sense of the word, general practitioner care.

Table 6. Key medical history questions to objectively assess preterm birth.

Key medical history questions	Prognostic evaluation
Gestational week (GW)?	< 30 gw (very preterm infant) → Long-term risks increased 30 < gw < 37 (moderately preterm or late preterm infant) → Moderate developmental risks, increased after perinatal complications
Birth weight?	< 1500 g (very low birth weight infant) → Long-term risks increased 1500 g < birth weight < 2500 g (low birth weight preterm or hypotrophic full-term infant) → Moderate developmental risks, increased after perinatal complications
Cause (as far as known)?	Infection (amniotic infection syndrome; common!) → Adverse acute outcome typical Intrauterine growth restriction → Long-term metabolic sequelae typical
Ventilation (as far as known)?	Prolonged ventilation/oxygen dependence → Predisposition to long-term pulmonary (and neurological) sequelae
Complications (as far as known)?	Intracranial hemorrhage, hydrocephalus, retinopathy, bowel surgery etc. → Predisposition to particular organ complications and general developmental retardation
Are old medical reports available?	Detailed perinatal history as a basis for an individual risk assessment and personalized prevention

The questions take into consideration the fact that the cause of preterm birth and the extent of possible complications are of similar significance for the long-term prognosis as is prematurity in itself. The threshold below which one refers to a “very low birth weight infant” and, at the same time, the long-term risks significantly increase is a birth weight of 1500 g, which equates to a gestational age of 30 weeks of gestation (GW). If a preterm infant at 30 GW weighs only around 1000 g, significant intrauterine growth restriction is additionally present.

Questions on the article in issue 31–32/2021:

Adults Born Preterm: Long-Term Health Risks of Former Very Low Birth Weight Infants

The submission deadline is 8 August 2022. Only one answer is possible per question. Please select the answer that is most appropriate.

Question 1

What birth weight is defined as the threshold above which one refers to “very low birth weight infants”?

1. < 1300 g

2. < 1800 g

3. < 1200 g

4. < 1500 g

5. < 2000 g

Question 2

Very low birth weight infants account for what percentage of all births?

1. Approximately 0.1%

2. Approximately 1%

3. Approximately 5%

4. Approximately 10%

5. Approximately 20%

Question 3

The most robust data on long-term outcomes in very low birth weight infants come from which countries?

1. Germany and France

2. Great Britain and the Netherlands

3. Asian countries

4. Central African countries

5. Scandinavian countries

Question 4

When was surfactant replacement therapy introduced for the treatment of fetal lung immaturity?

1. In the 1960s

2. In the 1970s

3. In the 1980s

4. In the 1990s

5. In the 2000s

Question 5

In a large Swedish collective, the risk for manifest diabetes mellitus in former preterm infants (23–28 GW) aged between 26 and 37 years was investigated. What was the reported relative risk?

1. aOR 0.7

2. aOR 1.5

3. aOR 2.0

4. aOR 2.5

5. aOR 3.1

Question 6

In the text, what factors are associated with a propensity to arterial hypertension in former very low birth weight infants?

1. Altered geometry of the left ventricular myocardium and rarefication of the postcapillary resistance vessels

2. Dysregulation of vasoconstriction and altered geometry of the atrial myocardium

3. Altered geometry of the aortic arch and increased venule wall stiffness

4. Altered geometry of the left ventricular myocardium and rarefication of the capillary circulation

5. Reduced wall stiffness of the large arteries and altered atrial geometry

Question 7

According to a meta-analysis of long-term studies on former very low birth weight infants (follow-up to the age of 32 years), which diagnosis was made in approximately every fifth patient?

1. Depression

2. Severe asthma

3. Retinal detachment

4. Diabetes mellitus

5. Attention deficit hyperactivity disorder

Question 8

In relation to which bone structure has reduced bone density been more frequently reported in former preterm infants with intrauterine growth restriction?

1. Vertebral bodies of the lumbar spine

2. Femoral neck

3. Carpal bone

4. Ribs

5. Vertebral bodies of the thoracic spine

Question 9

A meta-analysis to determine pulmonary risks in adults born preterm investigated the reduction in forced expiratory volume in 1 s compared to full-term infants. To what extent was the forced expiratory volume in 1 s on average reduced in subjects that still required oxygen at the age of 36 postmenstrual weeks (BPD₃₆) following preterm birth?

1. Approximately 3%

2. Approximately 5%

3. Approximately 10%

4. Approximately 20%

5. Approximately 30%

Question 10

Which pre- or perinatal factor promotes in particular the development of metabolic syndrome in later life via what is referred to as “fetal programming”?

1. Perinatal infections

2. Prenatal emotional stress

3. Delivery by emergency cesarean section

4. Birth after > 40 GW

5. Intrauterine growth restriction