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.

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.

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.

Cause-specific infant mortality in a population-based Swedish study of term and post-term births: the contribution of gestational age and birth weight.

OBJECTIVE: To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants. DESIGN: Observational, retrospective nationwide cohort study. SETTING: Sweden 1983-2006. PARTICIPANTS: 2 152 738 singleton non-malformed infants born at 37 gestational weeks or later. MAIN OUTCOME MEASURES: Infant, neonatal and postneonatal mortality and causes of infant death. RESULTS: Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms. CONCLUSION: Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.