Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study.

OBJECTIVES: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). METHODS: This population-based cohort study utilised Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within one year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes, and corticosteroids). Modified Poisson regression models with robust variance estimated risk ratios and 95% confidence intervals (RR 95%CI). RESULTS: We included 1,007 births (453 exposed) and 2,500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed, and unexposed groups were 3.6%, 3.7%, and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6%, and 4.3%, respectively. The adjusted RRs (95%CI) were 1.29 (0.65-2.56) in the SLE cohort, 1.32 (0.56-3.13) in the RA cohort, and 1.30 (0.76-2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings. CONCLUSIONS: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy.

Neurological development in children born moderately or late preterm: national cohort study.

OBJECTIVE: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term). DESIGN: Nationwide cohort study. SETTING: Sweden. PARTICIPANTS: 1 281 690 liveborn singleton children without congenital malformations born at 32+0 to 41+6 weeks between 1998 and 2012. MAIN OUTCOME MEASURES: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment. RESULTS: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term. CONCLUSIONS: The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.

Identification of irritable bowel syndrome in the Swedish National Patient Register: a validation study.

BACKGROUND AND OBJECTIVE: National patient registers are valuable in epidemiological studies. To ensure high-quality data for studies of irritable bowel syndrome (IBS), this study aimed to validate the ICD-10 code for IBS in the Swedish National Patient Register. METHODS: The positive predictive values (PPV) for IBS defined by the Rome criteria were calculated based on a review of medical records of randomly selected individuals with a first-ever diagnostic listing of IBS in the Swedish National Patient register in the year 2005 (Rome II criteria) or 2010 (Rome III criteria). KEY RESULTS: 340 medical records were reviewed (172 from 2005 and 168 from 2010). The majority of patients were females (74%), and the mean age was 42 years. IBS used in any type of department had a PPV of 76% (95% confidence interval 71-80%), which increased to 80% (76-84%) when we included individuals likely to have IBS but where information about some aspects of the Rome criteria was lacking in the medical record. Two highly specialized gastroenterological departments had the best PPV, 96%, while departments of internal medicine in general had a PPV of 82% (80-95%). The PPV for the IBS subtype was 62% (55-67%). The PPVs were not significantly different comparing the two time periods investigated. CONCLUSION AND INFERENCES: The validity of a register-based definition of IBS in the Swedish National Patient register is high and can be used to identify patients with IBS in observational research. The data source, i.e., type of hospital and department, influences reliability.

The Stockholm-Gotland perinatal cohort-A population-based cohort including longitudinal data throughout pregnancy and the postpartum period.

BACKGROUND: Register-based reproductive and perinatal databases rarely contain detailed information from medical records or repeated measurements throughout pregnancy and delivery. This lack of enriched pregnancy and birth data led to the initiation of the Swedish Stockholm-Gotland Perinatal Cohort (SGPC). OBJECTIVES: To describe the strengths of the SGPC, as well as the unique research questions that can be addressed using this cohort. POPULATION: The SGPC is a prospectively collected, population-based cohort that includes all births (from 22 completed gestational weeks onwards) between 1 January 2008 and 15 June 2020 in the Stockholm and Gotland regions of Sweden (335,153 singleton and 11,025 multiple pregnancies). DESIGN: Descriptive study. METHODS: The SGPC is based on the electronic medical records of women and their infants. The medical record system is used for all antenatal clinic visits and admissions, delivery and neonatal admissions, as well as postpartum clinical visits. SGPC has been further enriched with data linkages to 10 Swedish National Health Care and Quality Registers. PRELIMINARY RESULTS: In contrast to other reproductive and perinatal databases available in Sweden, including the Medical Birth Register and the Pregnancy Register, SGPC contains highly detailed medical record data, including time-varying serial measurements for physiological parameters throughout pregnancy, delivery, and postpartum, for both mother and infant. These strengths have enabled studies that were previously inconceivable; the effects of serial measurements of pregnancy weight gain, changes in haemoglobin counts and blood pressure during pregnancy, fetal weight estimations by ultrasound, duration of stages and phases of labour, cervical dilatation and oxytocin use during delivery, and constructing reference curves for umbilical cord pH. CONCLUSIONS: The SGPC-with its rich content, repeated measurements and linkages to numerous health care and quality registers-is a unique cohort that enables high-quality perinatal studies that would otherwise not be possible.

Low Apgar score and need for resuscitation increased the probability of receiving therapeutic hypothermia more strongly than acidosis at birth.

AIM: The aim of this study was to investigate how individual markers for birth asphyxia, so-called A criteria, were associated with the probability of receiving therapeutic hypothermia. METHODS: This population-based cohort study included 1336 live-born singleton term infants with any A criterion in the Stockholm-Gotland Region, Sweden during 2008 to 2014. The Swedish Neonatal Quality Register and National Patient Register were used for data collection. Results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: There were 89 infants, 44 boys and 45 girls with mean gestational age 40.5 weeks, who received therapeutic hypothermia. Low Apgar score, aOR 12.44 (95% CI 5.99-25.86), and resuscitation, aOR 9.18 (95% CI 3.77-22.34), were strongly associated with therapeutic hypothermia. A pH <7.0 was less associated with the outcome, aOR 2.02 (95% CI 1.02-4.0). No infant who received therapeutic hypothermia fulfilled the criteria of base deficit ≥16 mmol/L only. CONCLUSION: A low Apgar score of and/or a need for resuscitation is more relevant for identifying infants eligible for therapeutic hypothermia, compared to other A criteria. This knowledge could be used clinically to identify cases for review and avoid unnecessary monitoring of infants.

Validation of central nervous system-induced seizures and other neurological variables in the Swedish Neonatal Quality Register.

AIM: We sought to validate neurological variables and relevant International Classification of Diseases, Tenth Revision (ICD-10) codes in the Swedish Neonatal Quality (SNQ) Register. METHODS: Register data were collected for 351 neonates, born between January 2009 and December 2016, who were treated at a neonatal unit in the Stockholm region on 385 occasions. They were eligible if the check-box for central nervous system (CNS)-induced seizures was ticked. The Register data, including relevant ICD-10 codes, were validated by checking the patients' electronic medical charts. RESULTS: Most of the neonates were born at term (76%) and weighed >2500 g (80%). The variable CNS-induced seizures had a positive predictive value of 46%. The ICD-10 diagnosis P90.9A had a positive predictive value of 90%. This comprises seizures validated with electroencephalography, amplitude-integrated electroencephalography or continuous function monitoring. The majority of the associated neurological variables in the Register had positive predictive values above 85%. CONCLUSION: When the check-box was ticked for central nervous system-induced seizures, most of the neurological variables in the Register had high validity. However, the CNS-induced seizures variable per se had a lower positive predictive value. Future SNQ Register-based studies of such neonatal seizures should also include ICD-10 P90.9A.

Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms.

AIM: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. METHODS: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8 weeks after diagnosis are presented, and follow-up protocols are suggested. RESULTS: We identified 152 cases, and 133 (87%) participated. When followed up 2 weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8 weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. CONCLUSION: More than a third (36%) of the patients had persistent symptoms 8 weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.

Neonatal Morbidities in Infants Born Late Preterm at 35-36 Weeks of Gestation: A Swedish Nationwide Population-based Study.

OBJECTIVE: To assess risk for neonatal morbidities among infants born late preterm at 35-36 gestational weeks, early term (37-38 weeks), and late-term (41 weeks) infants, compared with full-term (39-40 weeks) infants. STUDY DESIGN: This nationwide population-based cohort study included 1 650 450 non-malformed liveborn singleton infants born at 35-41 weeks between 1998 and 2016 in Sweden. The relative risks for low Apgar score (0-3) at 5 minutes; respiratory, metabolic, infectious, and neurologic morbidities; and severe neonatal morbidity (composite outcome) were adjusted for maternal, pregnancy, delivery, and infant characteristics. RESULTS: Compared with infants born at 39-40 weeks, the adjusted relative risks and proportions of infants born at 35-36 weeks were higher for metabolic morbidity 7.79 (95%, 7.61 to 7.97; 33.75% vs 3.11%), respiratory morbidity 5.54 (95% CI, 5.24 to 5.85; 5.49% vs 0.75%), severe neonatal morbidity 2.42 (95% CI, 2.27 to 2.59; 3.40% versus 1.03%), infectious morbidity 1.98 (95% CI, 1.83 to 2.14; 2.53% vs 0.95%), neurologic morbidity 1.74 (95% CI, 1.48 to 2.03; 0.54% vs 0.23%), and low Apgar score 2.07 (95% CI, 1.72 to 2.51; 0.42% vs 0.12%). The risks for respiratory, severe neonatal morbidity, infectious, neurologic morbidities, and low Apgar score were highest at 35 weeks, gradually decreased until 39 weeks, and increased during 39-41 weeks. CONCLUSIONS: Infants born late preterm at 35-36 weeks of gestation are at increased risk of neonatal morbidities, although the absolute risks for severe neonatal morbidities are low. Our findings reinforce the need of preventing late preterm delivery to decrease the burden of neonatal morbidity and help professionals and families with a better risk assessment.

Long-term Follow-up for Missed Cases of Eosinophilic Esophagitis in Children With Previous Foreign Body in the Esophagus.

OBJECTIVES: A foreign body impacted in the esophagus could be a sign of eosinophilic esophagitis (EoE). Our aim was to investigate if children previously diagnosed with a foreign body in the esophagus had a missed diagnosis of EoE. METHODS: In this population-based longitudinal study, all children (0-18 years) diagnosed with a foreign body in the esophagus in Stockholm, Sweden 2006 to 2016, were identified. In addition to a review of medical files, each family was contacted (n = 325) and asked standardized questions. Children with symptoms indicating EoE were offered esophagogastroduodenoscopy (EGD). RESULTS: We found 325 pediatric cases of foreign body. Two hundred and seven (64%) underwent an endoscopy at the event, 3 of these had biopsies taken, whereby 2 were diagnosed with EoE. Six additional patients were diagnosed with EoE between the initial event and the study follow-up. Children with persisting symptoms suggestive of EoE at the follow-up (n = 21), were offered EGD whereof 7 accepted. Four new cases of EoE were found. Hence, 12 (3.7%) of the children with a previous foreign body, either spontaneously released or endoscopically removed, were diagnosed with EoE. In the structured interview, dysphagia, food impactions and drinking excessively with meals, as well as food allergies, were significantly more common in EoE patients. CONCLUSIONS: Children with a foreign body in the esophagus are at risk of having EoE. Biopsies should be taken during foreign body removal and questions about swallowing problems and allergic diseases should be carefully explored also in children who do not need EGD because of spontaneous release.

Diagnostic values of the femoral pulse palpation test.

OBJECTIVES: To calculate diagnostic values of the femoral pulse palpation to detect coarctation of the aorta or other left-sided obstructive heart anomalies in newborn infants. DESIGN: Population-based cohort study. SETTING: Stockholm-Gotland County 2008-2012. PATIENTS: All singleton live-born infants without chromosomal trisomies, at ≥35 gestational weeks, followed-up until 1-2 years of age. MAIN OUTCOME MEASURES: Diagnostic values and ORs for the femoral pulse test and subsequent diagnosis of coarctation of the aorta or left-sided obstructive heart malformation. RESULTS: Among the 118 592 included infants, 432 had weak or absent femoral pulses at the newborn examination. Seventy-eight infants were diagnosed with coarcation of the aorta and 48 with other left-sided obstructive heart malformations. The diagnostic values for the femoral pulse palpation test to detect coarctation of the aorta were: sensitivity: 19.2%, specificity: 99.6, positive predictive value: 3.5% and negative predictive value: 99.9%. For left-sided heart malformations: sensitivity: 8.3%, specificity: 99.6%, positive predictive value: 0.9% and negative predictive value: 100%. Sensitivity for coarctation of the aorta increased from 16.7% when examined at <12 hours of age to 30.0% at ≥96 hours of age. CONCLUSIONS: The femoral pulse test to detect coarctation of the aorta and left-sided heart malformations has limited sensitivity, whereas specificity is high. As many infants with life-threatening cardiac malformations leave the maternity ward undiagnosed, further efforts are necessary to improve the diagnostic yield of the routine newborn examination.

[Born a few weeks too early; does it matter?] / Att födas några veckor för tidigt ­ spelar det någon roll?

Late and moderately preterm infants, born between 32+0/7 and 36+6/7 gestational weeks, comprise more than 80 % of all preterm infants and account for almost 40 % of all days of neonatal care. While their total number of days of care has not changed, an increasing part of their neonatal stay (from 29 % in 2011 to 41 % in 2017) is now within home care programmes. Late and moderate preterm birth is often complicated by respiratory disorders, hyperbilirubinemia, hypothermia and feeding difficulties. These infants also have an increased risk of perinatal death and neurologic complications. In the long run, they have higher risks of cognitive impairment, neuropsychiatric diagnoses and need for asthma medication. As young adults, they have a lower educational level and a lower average salary than their full-term counterparts. They also have an increased risk of long-term sick leave, disability pension and need for economic assistance from society.

Pre- and perinatal stress and irritable bowel syndrome in young adults - A nationwide register-based cohort study.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) is poorly understood. Animal and human data suggest that early life stress may induce long-term changes in the nociceptive circuitry, but conclusive studies are lacking. METHODS: We identified all Swedish children born between 1973 and 1992 in the Swedish Medical Birth Register. We had access to all diagnostic codes for specialized (nonprimary care) outpatient visits 2001-2009 (the National Patient Register) and identified individuals who were diagnosed with IBS (ICD-10 code: K58) after 18 years of age. We compared incidence of IBS in individuals with and without pre- and perinatal stress using multivariable logistic regression. KEY RESULTS: 2 056 430 children were included in the study. After turning 18 years, 14 382 of them were diagnosed with IBS in specialized outpatient care. Neither high, nor low birth weight was a risk factor for IBS in young adults. Preterm birth was associated with lower occurrence of IBS (adjusted OR 0.82 [0.75-0.90]) and vaginal instrumental delivery and Cesarean delivery were associated with slightly increased odds of IBS (adjusted OR 1.14 [1.06-1.24] and 1.09 [1.03-1.16] respectively). Neonatal distress and respiratory distress were not associated with future IBS. Female gender was by far the strongest risk factor for IBS in young adults (adjusted OR 3.48 [3.34-3.63]). CONCLUSIONS & INFERENCES: In this large population-based study, we found that mode of delivery was associated with an increased risk for IBS in young adulthood, while other proxies for pre- and perinatal stress were not. Female gender remains the most important risk factor for IBS.

Moderate neonatal hypoglycemia and adverse neurological development at 2-6 years of age.

To determine whether moderate neonatal hypoglycemia in otherwise healthy infants is associated with adverse neurodevelopmental outcome in pre-school children. Population-based cohort study with prospectively collected register data from Sweden. All singletons born July 1st 2008 through December 31st 2012 (n = 101,060) in the region were included. Infants with congenital malformations, infants treated in neonatal intensive care unit, infants with inborn errors of metabolism and infants to mothers with diabetes were excluded. Infants were followed-up until 2014, at 2-6 years of age. Exposure was neonatal moderate hypoglycemia. Main outcomes were a compiled neurological or neurodevelopmental outcome; any developmental delay; motor developmental delay; and cognitive developmental delay. In adjusted regression analyses, the odds ratio (OR) of any neurological or neurodevelopmental outcome was 1.48 (95% confidence interval: 1.17-1.88) in hypoglycemic compared to normoglycemic infants. The adjusted risk of any developmental delay was more than doubled (OR 2.53 [1.71-3.73]), the adjusted risk of motor developmental delay was almost doubled (OR: 1.91 [1.06-3.44]) and the adjusted risk of cognitive developmental delay was almost tripled (OR 2.85 [1.70-4.76]). Infants with early neonatal hypoglycemia (< 6 h) had a double risk (OR 1.94 [1.30-2.89]) of any neurological or neurodevelopmental outcome and a tripled risk of cognitive developmental delay (OR 3.17 [1.35-7.43]), compared to normoglycemic infants. In the first population-based study on this topic, we show that moderate neonatal hypoglycemia is associated with increased risks of impaired neurodevelopment. Current treatment routines for uncomplicated hypoglycemia should be followed.

Prolonged second stage of labor is associated with low Apgar score.

There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min <7 and <4. We found that the overall rates of 5 min Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 h from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 min generally increased with length of second stage of labor: 1 to <2 h: OR 1.78 (95% CI 1.19-2.66); 2 to <3 h: OR 1.66 (1.05-2.62); 3 to <4 h: OR 2.08 (1.29-3.35); and ≥4 h: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 min Apgar score.

Early Provision of Mother's Own Milk and Other Predictors of Successful Breast Milk Feeding after Very Preterm Birth: A Regional Observational Study.

BACKGROUND: Breast milk is associated with a lower risk of neonatal morbidity in very preterm infants. Despite the benefits, the duration of breastfeeding is shorter in very preterm infants than in term infants. OBJECTIVE: This study aimed to investigate how early provision of mother's own milk (MOM) and maternal and infant characteristics are related to breast milk feeding (BMF) between 36 and 40 weeks postmenstrual age (PMA) after very preterm birth. METHODS: A regional observational study of 138 singleton infants born at < 32 weeks of gestation in Stockholm, Sweden, was conducted. Data were derived from medical charts to investigate the association between early provision of MOM; maternal and infant characteristics; and exclusive, partial, or no BMF at 36 weeks PMA. Moreover, changes in BMF between 36 and 40 weeks PMA were studied. RESULTS: Most infants (80%) received MOM at 36 weeks PMA (55% exclusively, 25% partial). High provision of MOM at postnatal day 7 was associated with exclusive BMF at 36 weeks PMA, odds ratio (OR) 1.18 per 10 mL/kg MOM (95% confidence interval [CI], 1.06-1.32). Mothers born in non-Nordic countries provided MOM exclusively less often, adjusted OR 0.27 (95% CI, 0.10-0.69), compared to Nordic mothers. Between 36 and 40 weeks PMA, BMF decreased overall. This change was not associated with investigated predictors. CONCLUSION: It is possible to achieve high rates of BMF in very preterm infants. High intake of MOM early in the postnatal period is strongly related to exclusive BMF at 36 weeks PMA.

Perinatal conditions related to growth restriction and inflammation are associated with an increased risk of bronchopulmonary dysplasia.

AIM: Bronchopulmonary dysplasia (BPD) is a frequent chronic lung disease in preterm infants, and we aimed to identify factors associated with this condition in infants with respiratory distress syndrome (RDS). METHODS: This case-control study, using national Swedish data, included 2255 preterm infants, born before 33 gestational weeks. The 667 BPD cases were oxygen dependent at 36 weeks' postmenstrual age, and the 1558 controls only had RDS. Comparisons included perinatal conditions and pharmacological treatments. Adjusted odds ratios with 95% confidence intervals were calculated in a conditional logistic regression model, with gestational age as the conditioning term. RESULTS: An increased risk of BPD was associated with prelabour preterm rupture of membranes of more than 1 week (3.35, 2.16-5.19), small for gestational age (2.73, 2.11-3.55), low Apgar score (1.37, 1.05-1.81), patent ductus arteriosus (1.70, 1.33-2.18), persistent pulmonary hypertension (5.80, 3.21-10.50), pulmonary interstitial emphysema (2.78, 1.37-5.64), pneumothorax (2.95, 1.85-4.72), late onset infections (2.69, 1.82-3.98), intubation (1.56, 1.20-2.03), chest compressions (2.05, 1.15-3.66) and mechanical ventilation (2.16, 1.69-2.77), but not antenatal corticosteroids. CONCLUSION: Growth restriction and inflammation increased the risk of BPD in preterm infants and prelabour preterm rupture of membranes, small for gestational age, low Apgar score or need for resuscitation should raise clinical suspicions.

Maternal overweight and obesity in early pregnancy and risk of infant mortality: a population based cohort study in Sweden.

OBJECTIVE: To investigate associations between maternal overweight and obesity and infant mortality outcomes, including cause-specific mortality. DESIGN: Population based cohort study. SETTING AND PARTICIPANTS: 1,857,822 live single births in Sweden 1992-2010. MAIN OUTCOME MEASURES: Associations between maternal body mass index (BMI) in early pregnancy and risks of infant, neonatal, and postneonatal mortality, overall and stratified by gestational length and by causes of infant death. Odds ratios were adjusted for maternal age, parity, smoking, education, height, country of birth, and year of delivery. RESULTS: Infant mortality rates increased from 2.4/1000 among normal weight women (BMI 18.5-24.9) to 5.8/1000 among women with obesity grade 3 (BMI ≥ 40.0). Compared with normal weight, overweight (BMI 25.0-29.9) and obesity grade 1 (BMI 30.0-34.9) were associated with modestly increased risks of infant mortality (adjusted odds ratios 1.25 (95% confidence interval 1.16 to 1.35) and 1.37 (1.22 to 1.53), respectively), and obesity grade 2 (BMI 35.0-39.9) and grade 3 were associated with more than doubled risks (adjusted odds ratios 2.11 (1.79 to 2.49) and 2.44 (1.88 to 3.17)). In analyses stratified by preterm and term births, maternal BMI was related to risks of infant mortality primarily in term births (≥ 37 weeks), where risks of deaths due to birth asphyxia and other neonatal morbidities increased with maternal overweight and obesity. Obesity grade 2-3 was also associated with increased infant mortality due to congenital anomalies and sudden infant death syndrome. CONCLUSIONS: Maternal overweight and obesity are associated with increased risks of infant mortality due to increased mortality risk in term births and an increased prevalence of preterm births. Maternal overweight and obesity may be an important preventable risk factor for infant mortality in many countries.

Prenatal inflammatory risk factors for development of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious, chronic lung disease affecting preterm infants. OBJECTIVE: To identify prenatal risk factors for BPD, focusing on inflammation. METHODS: Observational cohort study including 106,339 preterm infants, live born before gestational week 37 + 0, from 1988 to 2009 in Sweden. A total of 2,115 infants were diagnosed with BPD, of which 1,393 were born extremely preterm, before gestational week 28 + 0. Information on risk factors was obtained from national health registers and included maternal chronic inflammatory diseases, pregnancy related diseases, and drugs related to treatment of inflammation or infection during pregnancy. Adjusted odds ratios (OR) were calculated in multivariable logistic regression models and are presented with 95% confidence intervals [95% CI]. RESULTS: Preeclampsia was the strongest risk factor for BPD [adjusted OR 2.04, 95% CI 1.83, 2.29]. For extremely preterm infants the adjusted OR was 1.33 [95% CI 1.08, 1.64]. Chorioamnionitis was associated with an increased risk of BPD, but only when including all infants in the analyses [OR 1.33, 95% CI 1.19, 1.48]. No apparent associations were found between maternal chronic inflammatory disease or use of anti-inflammatory drugs and the risk of BPD. Maternal diabetes mellitus, gestational diabetes and maternal use of antibiotics were associated with reduced risks of BPD. CONCLUSION: Preeclampsia related disorders increased the risk and maternal diabetes mellitus and gestational diabetes reduced the risk for BPD. As angiogenic factors play a role in preeclampsia and diabetes our findings suggest that an impaired angiogenesis may contribute to BPD development.

Risk factors for acute respiratory morbidity in moderately preterm infants.

BACKGROUND: Infants born preterm account for a substantial part of neonatal morbidity, with acute respiratory disorders being a dominating clinical problem. Whereas focus in recent studies has been on extremely and very preterm infants, less is known about contemporary rates and risk factors for acute respiratory morbidity in moderately and late preterm infants. The objective of this population-based Swedish study was to establish rates for different acute respiratory diseases in moderately preterm infants, and to identify maternal, obstetric and neonatal risk factors for the two most common diagnoses, transient tachypnoea of the newborn (TTN) and respiratory distress syndrome (RDS). METHODS: The study included 4679 moderately preterm [gestational age (GA): 30 to 34 weeks], 15 036 late preterm infants (GA 35 to 36 weeks) and 451 479 term infants (GA: 37 to 41 weeks). All infants were born in 2004-2008. RESULTS: In moderately preterm infants, risk factors for TTN in multivariable analyses were multiparity, caesarean section before and after onset of labour, male sex, Apgar score 4-6 at 5 min and lower GA. Risk factors for RDS were multiparity, caesarean section before and after onset of labour, male sex, Apgar score <7 at 5 min and lower GA. Preterm rupture of membranes, antenatal corticosteroid treatment and being small for gestational age reduced the risk of RDS. CONCLUSION: We conclude that acute respiratory morbidity in moderately preterm infants is common and predicted by multiparity, caesarean section, low Apgar score and male sex.