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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2009.11.017 Byline: Nisha I. Parikh (a), Sven Cnattingius (b), Paul W. Dickman (c), Murray A. Mittleman (a), Jonas F. Ludvigsson (b)(d), Erik Ingelsson (c) Abstract: Prior studies relating parity with maternal cardiovascular disease (CVD) have been performed in relatively small study samples without accounting for pregnancy-related complications associated with CVD. Author Affiliation: (a) Cardiovascular Division and Cardiovascular Epidemiology and Research Unit, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (b) Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Sweden (c) Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (d) Department of Pediatrics, Arebro University Hospital, Arebro, Sweden Article History: Received 18 September 2009; Accepted 18 November 2009

Background: In small clinical studies, preterm birth was associated with altered cardiac structure and increased cardiovascular mortality in the young.Objectives: The goal of this study was to determine the association between preterm birth and risk of incident heart failure (HF) in children and young adults.Methods: This register-based cohort study included 2,665,542 individuals born in Sweden from 1987 to 2012 who were followed up from 1 year of age to December 31, 2013. The main study outcome was diagnosis of HF in the National Patient Register or the Cause of Death Register. The association between preterm birth and risk of incident HF was analyzed by using a Poisson regression model. Estimates were adjusted for maternal and pregnancy characteristics, socioeconomic status, and maternal and paternal cardiovascular disease.Results: During 34.8 million person-years of follow-up (median 13.1 years), there were 501 cases of HF. After exclusion of 52,512 individuals with malformations (n = 196 cases), 305 cases of HF remained (0.88 per 100,000 person-years). Gestational age was inversely associated with the risk of HF. Compared with individuals born at term (≥37 weeks' gestation), adjusted incidence relative risks for HF were 17.0 (95% confidence interval [CI]: 7.96 to 36.3) after extremely preterm birth (<28 weeks) and 3.58 (95% CI: 1.57 to 8.14) after very preterm birth (28 to 31 weeks). There was no risk increase after moderately preterm birth (32 to 36 weeks) (relative risk: 1.36; 95% CI: 0.87 to 2.13).Conclusions: There was a strong association between preterm birth before 32 weeks of gestation and HF in childhood and young adulthood. Although the absolute risk of HF is low in young age, our findings indicate that preterm birth may be a previously unknown risk factor for HF. [ABSTRACT FROM AUTHOR]

Background: Pregnancy weight-gain z score charts have recently been proposed as a new tool for classifying gestational weight gain and establishing the link between weight gain and adverse maternal and infant outcomes. However, existing charts are few in number, were based on small sample sizes, and were not population based. Objective: We created population-based pregnancy weight-gain-for-gestational-age z score charts for Swedish women who were stratified by early pregnancy body mass index (BMI). Design: Serial prenatal electronic medical records were obtained from women who were receiving obstetrical care in the Swedish counties of Gotland and Stockholm. The study population was restricted to nonanomalous, singleton, term pregnancies with no prepregnancy hypertension or diabetes. A multilevel linear regression was used to express the repeated weight-gain measurements as a function of gestational age in underweight, normal-weight, overweight, and obese class I–III women. Observed weight-gain ranges were contrasted with current Institute of Medicine (IOM) pregnancy weight-gain recommendations. Results: A total of 711,615 serial prenatal weight measurements from 141,767 pregnant women were included. The smoothed means, SDs, and selected percentiles (3rd, 10th, 50th, 90th, and 97th) of weight gain were estimated for each week of gestation. The total weight gain and rate of weight gain decreased with increasing prepregnancy BMI. In all BMI categories, the observed range of pregnancy weight gain was considerably broader than the range currently recommended by the IOM. Conclusions: The presented population-based pregnancy weightgain charts can be used to express maternal weight gain as gestational age–standardized z scores with early pregnancy BMI taken into consideration. The z scores can be used to obtain a better understanding of the relation between pregnancy weight gain and maternal and infant health complications. [ABSTRACT FROM AUTHOR]

Objective: To provide risk estimates for celiac disease (CD) in Down syndrome (DS) compared with the general population. Study design: In this nationwide Swedish case-control study, we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of 2 populations: 11 749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh grade III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53 887 population-based controls matched for sex, age, calendar year of birth, and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. ORs were calculated using conditional logistic regression. Results: Of the 11 749 individuals with CD, 165 had a diagnosis of DS (1.4%) compared with 55/53 887 controls (0.1%). This corresponded to an OR of 6.15 (95% CI = 5.09-7.43) for subsequent CD in individuals with DS compared with the general population. The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child. Conclusions: We found a sixfold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD. [Copyright &y& Elsevier]

Background & Aims: Gastroesophageal reflux is common in infants during their first year of life, especially in those born preterm or small for gestational age (SGA). We assessed whether being born preterm or SGA increased the risk of developing Barrett's esophagus (BE) in adulthood. Methods: We performed a population-based case-control study of patients with BE (cases) that were diagnosed at 2 Swedish hospitals from January 1, 1986, through December 31, 2005. We identified the birth hospital of the cases; data on perinatal characteristics such as gestational age at birth and birth weight were collected from original birth records. We also obtained and collected information on the 3 singleton live births, of the same sex, born after each case at the same maternity ward (controls). In total, we analyzed data from 331 cases and 852 matched controls. We used conditional logistic regression to determine odds ratios (ORs), determined 95% confidence intervals (CIs), and adjusted for potential confounding factors. Results: Compared with infants born with a normal birth weight (3000–3999 g), infants with low birth weight (<2500 g) were at increased risk of BE (adjusted OR, 8.22; 95% CI, 2.83–23.88). This was mainly due to an effect of SGA rather than preterm birth. Specifically, compared with infants with normal birth weight for gestational age (25th–75th percentiles), the odds of BE among very SGA infants (<3rd percentile) was nearly tripled (adjusted OR, 2.95; 95% CI, 1.35–6.44). Conclusions: On the basis of a population-based study of patients with BE in Sweden, infants born SGA have a 3-fold increase in risk for developing BE as adults, compared with infants of normal birth weight for gestational age. [Copyright &y& Elsevier]

Background & Aims: The association between gastroesophageal reflux and esophageal adenocarcinoma is likely to be mediated by inflammation. Reflux is common in infancy; the esophageal mucosa of infants born preterm or small for gestational age (SGA) could be particularly vulnerable. We investigated the association between preterm or SGA birth and risk of esophagitis early in life. Methods: We analyzed data from the Swedish birth register and the Swedish patient register to identify birth characteristics of individuals with endoscopically verified esophagitis from 1973 to 2007 and to determine their outcomes (7358 cases). Five controls were selected randomly and matched with each case (N = 38,479). Multivariable conditional logistic regression models were used to provide odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding. Results: The risk of esophagitis was increased among individuals born preterm (≤32 gestational weeks) (OR, 2.74; 95% CI, 2.15–3.49) or SGA (OR, 1.49; 95% CI, 1.32–1.68). When data were stratified by age at diagnosis and by sex, different risk patterns appeared. Among individuals diagnosed with esophagitis 9 years of age and younger, the OR for prematurity was 6.82 (95% CI, 4.65–10.03) and the OR for SGA at birth was 1.98 (95% CI, 1.55–2.52). Furthermore, the association with preterm birth was stronger among males (OR, 9.88; 95%, CI 5.93–16.45) than females (OR, 3.41; 95% CI, 1.81–6.41), whereas the association with SGA was stronger among females (OR, 2.50; 95% CI, 1.76–3.55) than males (OR, 1.64; 95% CI, 1.16–2.30). The risk of being diagnosed with esophagitis at age 20 or younger was not associated with preterm birth (OR, 1.02; 95% CI, 0.64–1.63), but was associated with being SGA at birth (OR, 1.31; 95% CI, 1.11–1.54). Conclusions: Preterm birth is associated with esophagitis only during childhood, whereas SGA birth is associated with esophagitis during adolescence as well. The associations appear to differ between sexes. [Copyright &y& Elsevier]

Abstract: Objectives: to investigate long-term outcomes of mothers who have or have not held their stillborn baby, and predictors of having held the baby. Design: postal questionnaires. Setting: a nation-wide cohort study of mothers who gave birth to a singleton stillborn baby in Sweden in 1991. Participants: 314 out of 380 women answered the questionnaire and 309 reported whether or not they had held their baby. Measurements: scales measuring anxiety, depression and well-being. Findings: 126 (68%) mothers of 185 babies stillborn after 37 gestational weeks had held their baby and 82 (68%) mothers of 120 babies stillborn at gestational weeks 28–37 had also done so. Compared with mothers who agreed completely with the statement that staff gave enough support to hold the baby, mothers who did not agree were less likely to have held their baby [relative risk (RR) 4.1; 95% confidence interval (CI) 2.7–6.1], and mothers with a low level of education were less likely to have held their baby than mothers with a higher level of education (RR 2.2; 95% CI 1.3–3.8). Mothers who had not held their babies born after 37 gestational weeks had an increased risk of headache (RR 4.3; 95% CI 1.1–16.5), and they were less satisfied with their sleep (RR 2.7; 95% CI 1.5–5.0). The increased risk of long-term outcomes associated with not holding, compared with holding, a stillborn baby were less pronounced for women who gave birth at gestational week 28–37 compared with women who gave birth after 37 gestational weeks. Key conclusions: in this cohort, we found an overall beneficial effect of having held a stillborn baby born after 37 gestational weeks, whereas findings for having held a stillborn baby born at gestational weeks 28–37 are uncertain. The attitude of staff influenced whether or not the mother held her stillborn baby. Implications for practice: if the mother is guided by staff in a sensitive way to hold her stillborn term baby, the experience will possibly be beneficial for her in the long term. [Copyright &y& Elsevier]

Objectives: To examine whether the smaller size of infants born to primiparous, short, or thin mothers is associated with increased risks of perinatal mortality. Study design: We compared gestational age-specific patterns of “revealed” small-for-gestational-age (SGA) birth (number of SGA births expressed as a proportion of fetuses remaining in utero at each gestational age) with the patterns for perinatal mortality among singleton late fetal deaths and live births (n = 791,523) to Swedish mothers in 1992 to 2001. Results: Based on a single standard for SGA, primiparae were at substantially higher risk of revealed SGA throughout gestation, paralleling the pattern for perinatal mortality. However, for short and thin women, risks of revealed SGA were much more consistent with those for perinatal mortality when SGA was based on height-specific or body mass index–specific standards, respectively, rather than on the single standard. Overweight and obese mothers had lower revealed SGA rates based on either standard but higher perinatal mortality rates. Conclusions: Slower fetal growth due to maternal short stature or low prepregnancy body mass index appears to be physiologic, whereas the slower growth of fetuses born to primiparous women is associated with higher risks of perinatal death. [Copyright &y& Elsevier]

Objective: The objective of the investigation was to study the association between prior miscarriages and the risks of placental dysfunction disorders, including preeclampsia, stillbirth, birth of a small for gestational age (SGA) infant, placental abruption, and spontaneous preterm birth. Study Design: In a population-based cohort study including 619,587 primiparous women, we estimated risks of placental dysfunction disorders for women with 1 (n = 68,185), 2 (n = 11,410) and 3 or more (n = 3823) self-reported prior miscarriages. Risks were calculated as odds ratios by unconditional logistic regression analysis and adjustments were made for maternal age, early pregnancy body mass index, height, smoking habits, country of birth, years of formal education, in vitro fertilization, chronic hypertension, pregestational diabetes, hypothyroidism, systemic lupus erythematosis, fetal sex, and year of childbirth. Results: Compared with women with no prior miscarriage, women with 1 prior miscarriage had almost no increased risks. Women with 2 prior miscarriages had increased risks of spontaneous preterm birth, preterm (<37 weeks) SGA infant, and placental abruption. The rates of all disorders were higher for women with 3 or more prior miscarriages compared with women without prior miscarriages: preeclampsia, 5.83% vs 4.27%; stillbirth, 0.69% vs 0.33%, SGA infant, 5.09% vs 3.22%, placental abruption, 0.81% vs 0.41%; and spontaneous preterm birth, 6.45% vs 4.40%. The adjusted odds ratios for preterm (<37 weeks) disorders in women with 3 prior miscarriages were approximately 2. Conclusion: History of 2 or more miscarriages is associated with an increased risk of placental dysfunction disorders and should be regarded as a risk factor in antenatal care. [Copyright &y& Elsevier]

Background & Aims: Many patients with celiac disease experience malabsorption, weight loss, and anemia; undiagnosed celiac disease during pregnancy has been linked with adverse outcomes. Studies of celiac disease and congenital malformations in offspring have been underpowered. We investigated the risk of congenital malformations among the offspring of parents with celiac disease. Methods: We performed a nationwide cohort study of data from linked health care registers in Sweden from 1973 through 2009. We collected histopathology data from 28 pathology departments in Sweden to identify individuals with celiac disease (based on the presence of villous atrophy). We estimated the risks of malformations in the offspring of mothers and fathers with and without celiac disease. Logistic regression was used to estimate adjusted prevalence odds ratios (aPORs) with 95% confidence intervals (CIs). Results: Among 11,382 offspring of mothers with celiac disease, there were 672 cases (5.9%) of malformation compared with 2098 cases (5.1%) among 40,922 offspring of mothers without celiac disease. Similarly, 352 (5.9%) of 6002 offspring of fathers with celiac disease and 1009 (5.1%) of 19,600 offspring of fathers without celiac disease had a malformation. In adjusted analyses, the offspring of mothers or fathers with celiac disease had a slightly increased risk of having children with malformations (for those with mothers with celiac disease: aPOR, 1.15; 95% CI, 1.05–1.26; for those with fathers with celiac disease: aPOR, 1.14; 95% CI, 1.00–1.29). However, these excess risks decreased or vanished entirely when we restricted our data to births since 2000 (for those with mothers with celiac disease: aPOR, 1.11; and 95% CI, 0.79–1.56; for those with fathers with celiac disease: aPOR, 1.01; 95% CI, 0.81–1.26). Conclusions: In a nationwide study, we found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. However, the excess risk is small; the upper limits of the CIs for malformation indicate a 29% maximum relative increase. [Copyright &y& Elsevier]

Objective: The purpose of this study was to compare the risk of surgically treated stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in relation to mode of delivery and age at first childbirth. Study Design: This was a cohort study. Data from the Swedish Medical Birth Register on women with only cesarean delivery (n = 30,880 women) or only vaginal delivery (n = 59,585 women) were compared with the Swedish Patient Register to calculate incidence rates and hazard ratios (95% confidence interval [CI]) for SUI and POP surgery. Results: In analyses that were stratified by age, vaginal delivery consistently increased the risks of SUI and POP surgery. Among vaginally delivered women who were ≥30 years old, incidence rates of POP surgery were 13.8 (95% CI, 12.7–15.1), and for younger women were 6.4 (95% CI, 6.0–6.8) per 10,000 person-years. Exclusion of instrumental vaginal delivery did not alter the conclusions. Conclusion: Increasing age at first delivery increased the risk of subsequent SUI and POP surgery after both vaginal and cesarean delivery. [ABSTRACT FROM AUTHOR]

Objective: Knowledge about the causes of placental dysfunction disorders is limited. We performed an intergenerational study, focusing on the risks of placental dysfunction disorders in mothers and fathers who had been born small for gestational age (SGA). Study Design: Using linked generational data from the Swedish Medical Birth Register from 1973-2006, we identified 321,383 mother-offspring units and 135,637 mother-father-offspring units. Results: Compared with mothers who had not been born SGA, mothers who had been born SGA had the following adjusted odds ratios: late preeclampsia, 1.41 (95% confidence interval [CI], 1.26–1.57); early preeclampsia, 1.87 (95% CI, 1.38–2.35); placental abruption, 1.60 (95% CI, 1.23–2.09); spontaneous preterm birth, 1.11 (95% CI, 1.00–1.23); and stillbirth, 1.24 (95% CI, 0.84–1.82). Compared with parents who had not been born SGA, the risk of preeclampsia was more than 3-fold increased if both parents had been born SGA, whereas if only the mother had been born SGA, the corresponding risk was increased by only 50%. Conclusion: There is an intergenerational recurrence of placental dysfunction disorders on the maternal side and most likely also on the paternal side. [ABSTRACT FROM AUTHOR]

Objective: To determine the gestational age (GA)–specific risks for neonatal morbidity and use of interventions in infants born at 30 to 34 completed gestational weeks. Study design: A population-based Swedish study including 6674 infants born during 2004–2008. Risks for neonatal morbidity and use of interventions were investigated with respect to GA and birth weight standard deviation scores. Results: Acute lung disorder was diagnosed in 28%, hypoglycemia in 16%, bacterial infection in 15% and hyperbilirubinemia in 59% of the infants. Thirty-eight percent had received antenatal steroid therapy, 43% nasal continuous positive airway pressure, 5.5% required mechanical ventilation, 5.2% were treated with surfactant, and 30% with antibiotic therapy. Neonatal morbidity rates increased with decreasing GA, with odds ratios for different outcomes ranging from 2.1 to 23 at 30 weeks compared with 34 weeks of GA. Low birth weight standard deviation scores was more common at lower GA and was associated with increased morbidity rates. Conclusions: Despite general advances in perinatal care, moderately preterm infants still have substantially increased risks for neonatal morbidity. Whereas the neonatal morbidity rate was similar to results of previous reports, management of respiratory problems differed markedly from other studies. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that preeclampsia partly shares pathophysiology with stillbirth, placental abruption, spontaneous preterm birth, and giving birth to a small-for-gestational-age infant, and that women who develop preeclampsia in the first pregnancy may have increased risks of the other outcomes in the second pregnancy, even in the absence of preeclampsia. Study Design: In a nationwide Swedish cohort (n = 354,676) we estimated risks of adverse outcomes in the second pregnancy related to preterm (<37 weeks) and term (≥37 weeks) preeclampsia in the first pregnancy, using women without preeclampsia in the first pregnancy as reference. Results: Women with prior preterm preeclampsia had, in second pregnancy, more than doubled risks of stillbirth, placental abruption, and preterm births, and an even greater risk of giving birth to a small-for-gestational-age infant. Conclusion: Women with previous preterm preeclampsia have increased risks of adverse pregnancy outcomes in a second pregnancy despite the absence of preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk for stress urinary incontinence and pelvic organ prolapse surgery related to vaginal birth or cesarean delivery. Study Design: A cohort study of all women having their first and all subsequent deliveries by cesarean (n = 33,167), and an age-matched sample of women only having vaginal deliveries (n = 63,229) between 1973 and 1983. Hazard ratios were calculated using Cox regression models with 95% confidence intervals. Results: Women only having vaginal deliveries had increased overall risks of incontinence (hazard ratio, 2.9; 95% confidence interval, 2.4–3.6) and prolapse surgery (hazard ratio, 9.2; 95% confidence interval, 7.0–12.1) compared with women only having cesarean deliveries. Conclusion: Having only vaginal childbirths was associated with a significantly increased risk of stress urinary incontinence and pelvic organ prolapse surgery later in life compared with only having cesarean deliveries. [ABSTRACT FROM AUTHOR]

Objective To investigate if repeat (≥3) fetal scalp blood sampling (FBS) is associated with increased risk of caesarean delivery and worse neonatal outcome than occasional (1–2) FBS. Study design Prospective cohort study of women undergoing intrapartum FBS at Karolinska University Hospital, Sweden. FBS with lactate analysis was performed if the attending doctor found the cardiotocography (CTG) tracing suspicious or abnormal. Lactate concentration was measured bedside. As a routine in all deliveries, acid-base analyses were performed on umbilical artery and vein blood immediately after delivery. Main outcome measures were metabolic acidemia in umbilical artery at delivery, Apgar score <7 at 5 min and caesarean delivery. Results During the study period there were 2134 FBSs performed on 1070 laboring women with a median of two samplings (range 1–8). There were no differences in Apgar score <7 at 5 min or metabolic acidemia in umbilical artery blood at birth between labors with 1–2 FBS and ≥3 FBS. Among women who underwent 1–2 FBS, 23% had a caesarean delivery as compared with 42% of those having ≥3 FBS. After adjustment for confounders, repeat FBS remained an independent risk factor for caesarean delivery (adj OR 2.05; 95%C.I 1.5–2.8). Conclusion Fetal monitoring with repetitive FBS (≥3) during labors with CTG changes is safe for the baby, but the rate of caesarean delivery is doubled as compared to labors where 1–2 FBS are needed. Still, more than 50% of women with repetitive FBS will be delivered vaginally, and 1/3 of these spontaneously. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a possible correlation between transvaginal ultrasound findings in miscarriages and cytogenetic analyses from chorionic villi obtained by dilatation and curettage. Design: Prospective, population-based study. Setting: University-based hospital. Patient(s): Five hundred seventy-six women with spontaneous miscarriage diagnosed between 6 and 12 completed pregnancy weeks. Intervention(s): Transvaginal ultrasonography and dilatation and curettage. Main Outcome Measure(s): Cytogenetic analyses and ultrasound measurement of embryonic pole. Result(s): The mean gestational age was 9.5 weeks. Chromosomal analyses were successful in 259 cases, 159 with cytogenetic abnormalities and 100 euploidy. Empty gestational sacs were equally often found in euploidy and aneuploidy, whereas small embryonic or fetal poles were significantly more often associated with aneuploidy. Conclusion(s): A smaller than expected fetal size when a miscarriage is diagnosed during the first trimester is significantly associated with a chromosomal aberration. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether interpregnancy maternal weight change (difference between body mass index [BMI] at the first antenatal visit of the second pregnancy and BMI at the first antenatal visit of the first pregnancy) or changes in smoking status between pregnancies is related to the sex ratio of the second pregnancy.Design: Population-based cohort study.Setting: Swedish Birth Registry.Participant(s): A total of 220,889 women who had their first two consecutive singleton births between 1992 and 2004. Both live births and stillbirths were included.Intervention(s): Analyses of data collected prospectively in nationwide registries.Main Outcome Measure(s): Male-to-female sex ratio of the second pregnancy.Result(s): The sex ratio of the second pregnancy increased linearly with the amount of maternal weight change from the first to the second pregnancies, from 1.024 in women who lost more than 1 unit BMI to 1.080 in women who gained 3 or more units. This association was independent of obstetric complications, length of the interpregnancy interval, and maternal sociodemographic characteristics at the second pregnancy. Change in maternal smoking status from the first to the second pregnancies was not significantly related to the sex ratio of the second pregnancy.Conclusion(s): There could be a causal relation between prepregnant maternal weight gain and the sex ratio of the offspring. [ABSTRACT FROM AUTHOR]

Objective: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons.Design: Nationwide prospective study.Setting: Sweden.Patient(s): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection.Intervention(s): None.Main Outcome Measures(s): Infant (<1 year) and childhood (1-18 years) mortality.Result(s): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years.Conclusion(s): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos. [ABSTRACT FROM AUTHOR]

Objective: Ophthalmologic complications after preterm birth are common. Small studies show an association between retinopathy of prematurity and later retinal detachment. There are no population-based studies of preterm birth and risk of retinal detachment, which was the objective of the current investigation. Design: Nationwide Swedish cohort study based on population registries. Participants: Of 3 423 697 subjects born in Sweden, 1 271 725 were born between 1973 and 1986 (i.e., before the national screening program for retinopathy of prematurity started), and 2 151 972 were born between 1987 and 2008. The participants were followed up from 1 year of age until 2009. Methods: Unadjusted and adjusted hazard ratios (HRs) for retinal detachment were calculated using Cox proportional hazards regression. Main Outcome Measures: Incident retinal detachment, as defined by a diagnosis in the Swedish Patient Register (both inpatient and hospital-based outpatient data). Results: During follow-up (median follow-up, 17.4 years), 1749 subjects were diagnosed with retinal detachment. Among the 188 852 subjects born prematurely (i.e., at <37 weeks of gestation), there were 124 cases of retinal detachment, of which 42 occurred in the 20 470 subjects born before 32 weeks of gestation. Compared with subjects born at term (37–41 weeks), the adjusted HR for retinal detachment after extremely preterm birth (<28 weeks of gestation) was 19.2 (95% confidence interval [CI], 10.3–35.8) for births between 1973 and 1986 and 8.95 (95% CI, 3.98–20.1) for births between 1987 and 2008. The corresponding HRs in subjects born very prematurely (28–31 weeks) were 4.32 (95% CI, 2.70–6.90) and 2.80 (95% CI, 1.38–5.69), respectively. Moderately preterm birth (32–36 weeks) was not associated with an increased risk of retinal detachment. Conclusions: Birth before 32 weeks of gestation is associated with a substantially increased relative risk of retinal detachment. These findings may have implications for ophthalmologic follow-up of children and adults born very prematurely. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Abstract: We investigated whether infections with Parvovirus B19 and Herpes viruses in early pregnancy increase risks of second trimester miscarriage or delivery before 32 gestational weeks. Blood samples taken in early pregnancy were analyzed for Parvovirus B19 or Herpes viruses. Viremia was found in blood samples of 11 (4.7%) women with second trimester miscarriage and 10 (3.7%) women with very preterm birth, compared to 5 (1.7%) women who delivered at term, corresponding to adjusted odds ratios [95% CI] of 3.32 [0.93, 11.8] and 2.21 [0.71, 6.84], respectively. In stratified analyses, Parvovirus B19 viremia was associated with adjusted odds ratios of 3.76 [0.77, 18.3] for second trimester miscarriage and 2.66 [0.64, 11.1] for very preterm birth. Corresponding odds ratios for Human Herpes virus 6 viremia was 2.52 [0.33, 19.5] and 1.08 [0.14, 8.08], respectively. In conclusion, this study lends some support to the hypothesis that women with viremia in early pregnancy may face an increased risk of second trimester miscarriage or very preterm birth. Studies with larger sample sizes are needed. [Copyright &y& Elsevier]

Objective: To determine whether low birth weight increases the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and early adolescence.Method: In a population-based sample of 1,480 twin pairs born in the period 1985-1986 ascertained from the Swedish Twin Registry, birth weight was collected prospectively through the Medical Birth Registry. ADHD symptoms were measured with a 14-item checklist covering DSM-III-R criteria (parental rating) at age 8 to 9 years and 13 to 14 years. We used both a dichotomous approach for birth weight (>400 g or 15% weight difference) and ADHD (eight or more symptoms) and continuous measures to investigate between- and within-twin pair effects.Results: Our results showed that low birth weight was a risk factor for symptoms of ADHD and the associations did not diminish when we controlled for genetic influence. The lighter twin in birth weight-discordant pairs had on average 13% higher ADHD symptom score at age 8 to 9 years (p = .006) and 12% higher ADHD score at age 13 to 14 years (p = .018) compared with the heavier twin. The genetic correlations suggest modest or no genetic overlap between birth weight and ADHD.Conclusions: The hypothesis that low birth weight is associated with the development of ADHD symptoms was supported in this prospective twin study. Fetal growth restriction seems to represent a modest but fairly consistent environmental influence on the development of ADHD symptoms. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the cytochrome P450 1B1 (CYP1B1) Val432Leu polymorphism is associated with risk of miscarriage. We also analyzed the possible interaction between this polymorphism and caffeine intake. Design: The population-based case-control study included 507 women with miscarriage in the first trimester of pregnancy and 908 controls with a normal first-trimester pregnancy. The controls were frequency matched to cases. The material was analyzed taking maternal age, smoking habits, alcohol intake, caffeine intake, fetal karyotype, nausea, and vomiting into consideration. Setting: University hospital and primary care facility. Main Outcome Measure(s): CYP1B1 Val432Leu genotype frequencies in cases and controls. Result(s): Carriers of the CYP1B1 432 Val/Val genotype were at a higher risk of miscarriage in the first trimester of pregnancy (odds ratio = 1.46; 95% confidence interval, 1.02–2.08). We also found a significant interaction between genotype and caffeine intake. Conclusion(s): CYP1B1 Val432Leu polymorphism is associated with first-trimester miscarriage, and it may also modify the risk among coffee drinkers. [Copyright &y& Elsevier]

Objective: To investigate associations between depression, anxiety, and antidepressants before in vitro fertilization (IVF) and IVF cycle outcomes, including pregnancy, live birth, and miscarriage.Design: Nationwide register-based cohort study.Setting: Not applicable.Patient(s): Nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction, January 2007 to December 2012 (n = 23,557).Intervention(s): Not applicable.Main Outcome Measure(s): Associations between diagnoses of depression/anxiety, antidepressants, and IVF cycle outcome evaluated using logistic regression to produce adjusted odds ratios (AOR) and 95% confidence intervals (CI).Result(s): In total, 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their IVF first cycle. The odds for pregnancy and live birth were decreased (n = 1,044; AOR = 0.86; 95% CI, 0.75-0.98; and AOR = 0.83; 95% CI, 0.72-0.96, respectively). For women with a prescription for a selective serotonin reuptake inhibitor (SSRI) only (n = 829), no statistically significant associations were found. Women with non-SSRI antidepressants (n = 52) were at reduced odds of pregnancy (AOR = 0.41; 95% CI, 0.21-0.80) and live birth (AOR = 0.27; 95% CI, 0.11-0.68). Women with a depression/anxiety diagnosis with no antidepressant (n = 164) also had reduced odds of pregnancy (AOR = 0.58; 95% CI, 0.41-0.82) and live birth (AOR = 0.60; 95% CI, 0.41-0.89). Among the women who became pregnant (39.7%), there were no statistically significant associations between exposure and miscarriage except for the women taking non-SSRI antidepressants (AOR = 3.56; 95% CI, 1.06-11.9).Conclusion(s): A diagnosis of depression/anxiety and/or treatment with antidepressants before IVF was associated with slightly reduced odds of pregnancy and live birth. Women with the presence of depression/anxiety without antidepressants had a more pronounced reduction in odds, implying that the underlying disorder is important for the observed association. [ABSTRACT FROM AUTHOR]