Premature birth and low birthweight are associated with a lower rate of reproduction in adulthood: a Swedish population-based registry study.

BACKGROUND: The aim of this study was to investigate if individuals born with sub-optimal birth characteristics have reduced probability of reproducing in adulthood. METHODS: Using population-based registries, the authors included 522 216 males and 494 692 females born between 1973 and 1983 and examined their reproductive status as of 2006. Outcome measure was the hazard ratio (HR) of reproducing. Adjustments were made for socio-economic factors. RESULTS: Males and females born very premature displayed a reduced probability of reproducing [HR = 0.78, 95% confidence interval (CI): 0.70-0.86 for males; HR = 0.81, CI: 0.75-0.88 for females]. Likewise for very low birthweight (HR = 0.83, CI: 0.71-0.95 for males; HR = 0.80, 95% CI: 0.72-0.89 for females). Individuals born large for gestational age (LGA) displayed no significant changes. Males born small for gestational age (SGA) had a 9% lower reproductive rate (CI: 0.89-0.94) and that reduction increased as the individuals aged. Women born SGA tended to start reproducing at an earlier age. CONCLUSION: The results suggest that being born with low birthweight, premature or SGA (for males) is associated with a reduced probability of reproducing as an adult. LGA shows no statistically significant relationship with future reproduction.

Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?

BACKGROUND: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. AIM: To investigate the risk for ADHD in children conceived after IVF. METHODS: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. RESULTS: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio=1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR=1.40) than boys (OR=1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. CONCLUSIONS: The study suggests a weak association between IVF and drug treated ADHD.

Malignancies among women who gave birth after in vitro fertilization.

BACKGROUND: Relatively few studies published to date have investigated IVF and cancer risk. In this study we compared the occurrence of cancer in women who gave birth after IVF with all other women who gave birth in the study period. METHODS: All women who were treated with IVF and gave birth during the years 1982-2006 in Sweden were identified from all IVF clinics, and the occurrence of cancer in these women was identified by linkage with the nationwide Swedish cancer register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting for year of delivery and maternal age, parity and smoking. Cancer before IVF was only studied in first parity women. Specific cancer forms were also studied. RESULTS: Among 24058 women who had been treated with IVF, 1279 appeared in the cancer register. The total number of women studied in the population was 1 394 061, and 95 775 of these were registered in the cancer register. The risk for cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48] and was especially high for ovarian cancer (3.93). The risk for cancer after IVF was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than expected risk for breast and cervical cancer. The risk for ovarian cancer was increased but lower than the risk before IVF (2.13). CONCLUSIONS: Cancer or cancer treatment may increase the risk for infertility leading to IVF. After IVF, in most cases with treatment with fertility hormones, a significantly low cancer risk was found. Ovarian cancer showed an increased risk, although lower than before IVF. One possible reason is ovarian pathology causing both infertility and an increased cancer risk.

Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?

BACKGROUND: Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. AIMS: To follow up children conceived by IVF with respect to risk for CP. METHODS: Infants born after IVF were identified from all IVF clinics in Sweden 1982-2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. RESULTS: The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52-2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004-2007) when the twinning rate after IVF was <10%, the odds ratio for CP was 0.97 (95% CI 0.57-1.66). CONCLUSIONS: The moderately increased risk for CP was most likely a consequence of an increased risk of neonatal morbidity, notably associated with multiple births.

Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years.

BACKGROUND: Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment. METHODS: This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred. RESULTS: There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little. CONCLUSIONS: The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

Selected neonatal outcomes in dizygotic twins after IVF versus non-IVF pregnancies.

OBJECTIVE: To compare neonatal outcome among twins conceived after in vitro fertilisation (IVF) with that of spontaneously conceived twins. DESIGN: Comparison of different-sex (dizygotic) twins born after IVF with non-IVF dizygotic twins. SETTING: National health registers in Sweden. POPULATION: All births in Sweden during the period 1982-2007. METHODS: We studied gestational duration, lowest birthweight and birthweight difference in the twin pair, presence of one or two twins with a respiratory complication, and with jaundice in one or both twins. Risk estimates were calculated as odds ratios with adjustments for year of birth, maternal age, parity and smoking in pregnancy. MAIN OUTCOME MEASURES: Gestational duration, birth weight, respiratory complications, jaundice. RESULTS: We studied 1545 pairs of dizygotic twins born after IVF, and 8675 pairs of dizygotic twins where IVF was not known to have occurred. The risk for preterm delivery before 32 weeks of gestation was significantly increased among dizygotic twin pairs born after IVF compared with non-IVF dizygotic twin pairs. No significant difference in low birthweight or birthweight difference within twin pairs was seen. There was an increased occurrence of twin pairs with respiratory problems or jaundice, but only the latter diagnosis occurred in a statistically significant excess. CONCLUSIONS: The study confirms recent findings that IVF is associated with an increased risk for some neonatal complications, not only among singletons but also among twins.

Most very low birth weight subjects do well as adults.

AIM: To study health, quality of life, educational level and occupation in very low birth weight (VLBW) children in early adulthood and the relationship of the findings to neonatal risk factors and later handicap. METHODS: This is a prospective long-term follow-up study of a regional cohort of 20-year-old VLBW subjects (n = 77) of all surviving VLBW children (n = 86) and 69/86 term controls born in 1987-1988 in the south-east of Sweden. Postal questionnaires were used: 1. A study-specific form, 2. Medical Outcomes Study, Short Form (SF-36), 3. Sense of Coherence. RESULTS: VLBW subjects did not differ significantly from their controls in self-perceived health, use of tobacco, education, occupation and way of living, or scoring on SF-36 and Sense of Coherence. Sixteen had cerebral palsy, attention deficit hyperactivity disorder or isolated mental retardation, and these subjects differed significantly from controls on SF-36 in physical functioning and physical health score, but not on Sense of Coherence. VLBW subjects were significantly lighter and shorter than their controls. Extremely low birth weight (ELBW), bronchopulmonary dysplasia and intraventricular haemorrhage were significantly associated with poorer scores on physical function. CONCLUSION: The 20-year old VLBW subjects reported perceived health and managed transition to adulthood similar to controls. Handicapped subjects had poorer self-perceived physical function. ELBW and severe neonatal complications were associated with poorer self-perceived physical health.

Hospitalization in adolescence affects the likelihood of giving birth: a Swedish population-based register study.

AIM: To examine the effect of hospitalization during adolescence on the likelihood of giving birth. METHODS: 142 998 women born in 1973-75 were followed with the help of the Swedish Medical Birth Register (MBR) and the Swedish Total Population Register (TPR) up until the end of 2000 with respect to their likelihood of giving birth. All analyses were adjusted for parental socio-economic characteristics and factors related to the studied women's own birth. RESULTS: The likelihood of giving birth between 20 and 27 years of age was positively affected by hospitalization at least once during adolescence according to the Swedish Hospital Discharge Register (HDR); adjusted hazard ratio (HR) = 1.32, 95% confidence interval: 1.29-1.35. Women hospitalized due to genitourinary diseases, respiratory diseases, abdominal problems and abuse of alcohol and drugs were more likely to have given birth during the study period, while hospitalizations according to cerebral palsy and congenital malformations tended to decrease childbearing. Women hospitalized due to psychiatric diseases had an increase likelihood of given birth at 20-24 years but a reduced thereafter. CONCLUSION: A majority of the causes of hospitalization during adolescence increased the likelihood of giving birth between ages 20 to 27.

Intergenerational effects of preterm birth and reduced intrauterine growth: a population-based study of Swedish mother-offspring pairs.

OBJECTIVE: To estimate the intergenerational effects of preterm birth and reduced intrauterine growth. DESIGN: Population-based cohort study. SETTINGS: Mother-first-born offspring pairs recorded in the Swedish Medical Birth Registry. POPULATION: Children born before 2001 to 38 720 women born in 1973-75. METHODS: The relationships between the mother's and the child's birth characteristics were estimated using logistic regression analysis. Adjustments were made for smoking habits, body mass index (BMI), and current and childhood socio-economic conditions. Analyses were performed on all mother-offspring pairs and on the pairs for which information on neither of the included background variables was missing (n= 24 520). MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and small for gestational age (SGA) (<-2 SD of the Swedish standard). RESULTS: Mothers who themselves had been born preterm were not significantly more likely to deliver their own children preterm, compared with those who had been born at term (adjusted OR 1.24, 95% CI 0.95-1.62). Also, preterm birth in the mothers did not influence the occurrence of SGA in the children. However, the odds ratio for giving birth to SGA and preterm children, respectively, was higher among SGA mothers (OR 2.68, 95% CI 2.11-3.41 and OR 1.30, 95% CI 1.05-1.61). Mothers whose intrauterine growth was moderately reduced but who did not meet the criterion of being born SGA were also at higher risk of giving birth to both preterm and SGA children, respectively. CONCLUSIONS: The present study showed evidence of intergenerational effects of reduced intrauterine growth even when socio-economic factors as well as BMI and smoking were adjusted for. There was, however, no consistent intergenerational effect of preterm birth.

The probability of giving birth among women who were born preterm or with impaired fetal growth: a Swedish population-based registry study.

The primary aim of this study was to investigate whether women born prematurely or with impaired fetal growth have a reduced probability of giving birth. Using Swedish population-based registries, the authors identified 148,281 women born in 1973-1975 for follow-up until 2001. Of these women, 4.1% were born preterm and 0.32% very preterm, 0.29% were born with a very low birth weight, and 5.4% were small for gestational age. Outcome measures were the hazard ratios for giving birth during the study period. Adjustments were made for socioeconomic factors. Very-low-birth-weight women displayed a reduced probability of giving birth (hazard ratio = 0.74, 95% confidence interval: 0.60, 0.91), most apparent among women aged 25 or more years. There were also tendencies of reduced hazard ratios of giving birth among women born preterm or very preterm in this age interval. Women born small for gestational age (below -2 standard deviations) seemed to be more likely to have given birth (hazard ratio = 1.09, 95% confidence interval: 1.04, 1.14), but when a more extreme group of small-for-gestational-age women (below -3 standard deviations) was defined, the association was less evident (hazard ratio = 1.04, 95% confidence interval: 0.94, 1.16). The results suggest that very-low-birth-weight women and, possibly, women born preterm or very preterm have a reduced probability of giving birth, while the results regarding small for gestational age are less clear.

Can daily repeated doses of orally administered glucose induce tolerance when given for neonatal pain relief?

AIM: Orally administered sweet solutions have a pain-relieving effect during painful procedures in newborn infants. The underlying mechanism is not fully understood, but, from the results of animal research, an opioid-like mechanism is often suggested. The aim of this study was to determine whether repeated doses of orally administered glucose would cause tolerance to glucose. METHODS: Fifty-seven healthy, full-term infants were recruited on the day of birth to receive three daily doses of either 1 ml 30% glucose or sterile water for 3-5 d, after which routine blood samples were collected by heel-lance. All infants received 1 ml 30% glucose before the heel-lance was carried out. Crying time, Premature Infant Pain Profile scores and changes in heart rate were used as pain measures. RESULTS: No differences were found between the groups, either in demographic data or in the outcome variables. CONCLUSION: No tolerance was observed under the conditions prevailing in this study. However, we cannot rule out an endogenous opioid mechanism. What is clinically important is that repeated doses of glucose do not decrease the pain-relieving effect.

Very-low-birth-weight children at school age: academic achievement, behavior and self-esteem and relation to risk factors.

OBJECTIVE: To investigate school performance, behavior and self-esteem of children with very low birth weight (VLBW). METHODS: All children with birth weight below 1501 g (VLBW) and normal birth weight controls, born in the south-east region of Sweden during a 15-month period in 1987-88, were enrolled in a prospective follow-up study. At the age of 9 years, 81% and 82%, respectively, were re-examined regarding growth, neurofunctional classification, academic achievement tests, need for special education and behavioral problems. At 12 years, 89% and 76%, respectively, were re-examined regarding growth, neurofunctional classification, visual acuity and self-esteem. RESULTS: VLBW children were shorter and lighter, and differed from the controls with regard to neurological functional classification. They produced poorer results in most academic achievement tests. When the comparison was restricted to children with normal intelligence, almost all the differences in other academic achievements disappeared. VLBW children had more reading difficulties but were less often than expected defined as dyslexics compared to control children. We did not find any major disparity in visual acuity and self-esteem between the groups. Low Apgar scores, intracranial hemorrhage and the need for mechanical ventilation neonatally were associated with poorer results in most outcome measures. Neurofunctional assessments in early childhood were associated with most outcome measures. The mother's education was related to delayed reading skills and need for special education. CONCLUSIONS: Although VLBW children performed less well in most academic achievement tests and on some behavioral subscales, those who had a normal intellectual capacity did not differ in any important aspects from the controls.

Use of healthcare resources, family function, and socioeconomic support during the first four years after preterm birth.

OBJECTIVES: To assess the use of healthcare resources for preterm infants and to evaluate family function and socioeconomic support in a defined population from birth to 4 years of age. METHODS: In a prospective case-control study, 39 singleton preterm infants without prenatal abnormalities born during an 18 month period were studied together with their families. The population consisted of 19 very preterm infants (less than 32 weeks) and 20 randomised moderate preterm infants (32-35 weeks), and the control group comprised 39 full term infants. Contacts with medical services, child health services, and the social welfare system were registered, and family function and life events were studied. RESULTS: The preterm children were more often readmitted to hospital (odds ratio (OR) 6.6, 95% confidence interval (CI) 2.0 to 22.1) and had more outpatient attendances (OR 5.6, 95% CI 2.1 to 15.0) during their first year of life. Mothers in the preterm group more often used temporary parental allowance than the control mothers (p < 0.001). The number of contacts with the child health services and the social welfare system did not differ significantly from the controls. Neither was there any significant difference with regard to family function or life events at 4 years of age. CONCLUSIONS: A large proportion of the premature children used specialist care during the first years of life. However, the families of the preterm infants were socially well adapted up to four years after birth compared with the control families.

Can severity-of-illness indices for neonatal intensive care predict outcome at 4 years of age?

AIM: To test four neonatal severity-of-illness indices (CRIB, NTISS, SNAP, SNAP-PE) for their ability to predict short- and long-term outcome in very low-birthweight infants receiving neonatal intensive care. METHODS: Data on 240 newborns with birthweights below 1500 g from two Swedish neonatal units were collected. The predictive values of the indices for an adverse outcome in the neonatal period and at 4 y of age were compared with those of gestational age and birthweight. RESULTS: An early adverse outcome (in-hospital death, severe haemorrhagic-ischaemic brain lesion, retinopathy, chronic lung disease) was better predicted with CRIB (area under ROC curve (Az) = 0.87) and SNAP-PE (Az = 0.86), while SNAP-PE was best for predicting late problems (deviations in growth and psychomotor development, neurosensory impairment, difficulties in concentration, and impairment in vision, and hearing) (Az = 0.63). All indices predicted the early outcome better than the outcome at the 4-y follow-up. Severity-of-illness indices can be used as instruments to follow and improve the level of neonatal intensive care, but unfortunately seem to be of little value in long-term follow-up. CONCLUSION: CRIB and SNAP-PE indices are better in predicting hospital mortality than birthweight. None of the systems can predict adverse outcome at 4 y of age.

Neurological sequelae in children born after in-vitro fertilisation: a population-based study.

BACKGROUND: There is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls. METHODS: We did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres. FINDINGS: Children born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk. INTERPRETATION: Our study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.

[School maladjustment common among children with very low birth weight Special attention and support are required during school start]. / Skolsvårigheter vanliga hos barn med mycket låg födelsevikt. Extra uppmärksamhet och stöd behövs vid skolstart.

Children of very low birth weight (VLBW), defined as less than 1500 g, and normal birth weight controls (NBW) were enrolled in a long-term follow-up study. Five of 86 surviving VLBW children had a neurological handicap. Seventy VLBW children and 72 NBW children were re-examined at the age of nine, which entailed a neurological examination, a non-verbal intelligence test and a test for reading ability, mathematical skills and vocabulary. Their behavior was rated regarding hyperactivity, social behavior and fine and motor skills. The two groups differed with regard to the neurological examination and the tests, with poorer results shown for the low birth weight group. The VLBW children were also more hyperactive and scored lower on fine motor skills. Considering only those who scored normally as regards non-verbal intelligence (54% of VLBW children and 88% of controls), practically all differences disappeared.