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.

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.

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.

Maternal Diabetes Mellitus and Genital Anomalies in Male Offspring: A Nationwide Cohort Study in 2 Nordic Countries.

BACKGROUND: Pre-existing diabetes has been associated with an increased risk of congenital malformations overall, but studies on genital anomalies in boys are conflicting and possible causal mechanisms are not well understood. Previous studies have mainly assessed pregestational and gestational diabetes in combination. Yet considering the vulnerable time windows for the genital anomalies, associations could well differ between types of diabetes and between the 2 genital anomalies and we therefore aimed to study this further. METHODS: A population-based cohort study of 2,416,246 singleton live-born boys from Denmark (1978-2012) and Sweden (1987-2012) was carried out using Danish and Swedish register-based data. Using Cox regression models, we estimated hazard ratios for hypospadias and cryptorchidism according to maternal diabetes. We considered type and severity of diabetes, as well as timing of diagnosis in relation to birth. RESULTS: Pregestational type 1 diabetes was associated with a higher risk of both genital anomalies. The highest risks were seen for boys of mothers with diabetic complications (hazard ratio for hypospadias = 2.33 [95% confidence interval, 1.48, 3.66] and hazard ratio for cryptorchidism = 1.92 [95% confidence interval, 1.39, 2.65]). Gestational diabetes was associated with slightly increased risks of both genital anomalies. CONCLUSIONS: These results are consistent with the hypothesis that poor glycemic control may interfere with fetal genital development in the critical early period of organogenesis. Given the widespread and increasing occurrence of diabetes, these results are of public health importance.

Slow fetal growth between first and early second trimester ultrasound scans and risk of small for gestational age (SGA) birth.

OBJECTIVES: To investigate the association between fetal growth between first and early second trimester ultrasound scan and the risk of severe small for gestational age (SGA) birth. METHODS: This cohort study included 69 550 singleton pregnancies with first trimester dating and an early second trimester growth scan in Stockholm and Gotland Counties, Sweden between 2008 and 2014. Exposure was difference in biparietal diameter growth between observed and expected at the second trimester scan, calculated by z-scores. Risk of birth of a severe SGA infant (birth weight for gestational age by fetal sex less than the 3rd centile) was calculated using multivariable logistic regression analysis and presented as adjusted odds ratio (aOR). RESULTS: Parietal growth less than 2.5 percentile between first and second trimester ultrasound examination was associated with elevated risk of being born severe SGA. (aOR 1.67; 95% Confidence Interval 1.28-2.18). The risks of preterm severe SGA (birth before 37 weeks) and term severe SGA (birth 37 weeks or later) were at similar levels, and risk of severe SGA were also elevated in the absence of preeclampsia, hypertensive diseases or gestational diabetes. CONCLUSIONS: Fetuses with slow growth of biparietal diameter at ultrasound examination in early second trimester exhibit increased risk of being born SGA independent of gestational age at birth and presence of maternal hypertensive diseases or diabetes mellitus.

Apgar Score Components at 5 Minutes: Risks and Prediction of Neonatal Mortality.

BACKGROUND: The Apgar score consists of five components: heart rate, respiratory effort, muscle tone, reflex irritability, and colour. Although the Apgar score has been used for 60 years, the specific contribution of the Apgar score components with respect to risks and prediction of neonatal mortality remains unknown. Likewise, the value of reduced scores (including less than five Apgar score components) has rarely been investigated. METHODS: In a population-based cohort study of 148 765 liveborn singleton infants in Sweden 2008-2013, we investigated components of Apgar score at 5 min with respect to relative risks and prediction (using ROC curves, sensitivity, and positive predictive values) of neonatal mortality. RESULTS: Reduced values (0-1) of heart rate, respiratory effort, and colour were independently associated with increased relative risks of neonatal mortality. For the full Apgar score, the sensitivity and positive predictive values of neonatal mortality (cut-off ≤3) were by gestational age: ≤31 weeks: 56.1% and 49.2%; 32-36 weeks: 25.0% and 18.2%; and ≥37 weeks: 35.2% and 9.3%, respectively. When only heart rate and respiratory effort were considered (range 0-4; cut-off ≤2), corresponding values were 66.7% and 34.9%; 37.5% and 13.0%; and 46.3% and 7.6%, respectively. CONCLUSIONS: A reduced Apgar score has generally the same predictability of neonatal mortality as the full Apgar score. The full Apgar score or reduced scores may be better predictors of neonatal mortality in very preterm infants (≤31 weeks) than in infants with longer gestations.

Association Between Maternal Body Mass Index in Early Pregnancy and Incidence of Cerebral Palsy.

Importance: Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms. Objective: To study the associations between early pregnancy body mass index (BMI) and rates of cerebral palsy by gestational age and to identify potential mediators of these associations. Design, Setting, and Participants: Population-based retrospective cohort study of women with singleton children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012. Exposures: Early pregnancy BMI. Main Outcomes and Measures: Incidence rates of cerebral palsy and hazard ratios (HRs) with 95% CIs, adjusted for maternal age, country of origin, education level, cohabitation with a partner, height, smoking during pregnancy, and year of delivery. Results: Of 1 423 929 children included (mean gestational age, 39.8 weeks [SD, 1.8]; 51.4% male), 3029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up (risk, 2.13 per 1000 live births; rate, 2.63/10 000 child-years). The percentages of mothers in BMI categories were 2.4% at BMI less than 18.5 (underweight), 61.8% at BMI of 18.5 to 24.9 (normal weight), 24.8% at BMI of 25 to 29.9 (overweight), 7.8% at BMI of 30 to 34.9 (obesity grade 1), 2.4% at BMI of 35 to 39.9 (obesity grade 2), and 0.8% at BMI 40 or greater (obesity grade 3). The number of cerebral palsy cases in each BMI category was 64, 1487, 728, 239, 88, and 38; and the rates per 10 000 child-years were 2.58, 2.35, 2.92, 3.15, 4.00, and 5.19, respectively. Compared with children of normal-weight mothers, adjusted HR of cerebral palsy were 1.22 (95% CI, 1.11-1.33) for overweight, 1.28 (95% CI, 1.11-1.47) for obesity grade 1, 1.54 (95% CI, 1.24, 1.93) for obesity grade 2, and 2.02 (95% CI, 1.46-2.79) for obesity grade 3. Results were statistically significant for children born at full term, who comprised 71% of all children with cerebral palsy, but not for preterm infants. An estimated 45% of the association between maternal BMI and rates of cerebral palsy in full-term children was mediated through asphyxia-related neonatal morbidity. Conclusions and Relevance: Among Swedish women with singleton children, maternal overweight and obesity were significantly associated with the rate of cerebral palsy. The association was limited to children born at full term and was partly mediated through asphyxia-related neonatal complications.

Duration of second stage of labor and instrumental delivery as risk factors for severe perineal lacerations: population-based study.

BACKGROUND: We sought to investigate the impact of the duration of second stage of labor on risk of severe perineal lacerations (third and fourth degree). METHODS: This population based cohort study was conducted in the Stockholm/Gotland region, Sweden, 2008-2014. Study population included 52 211 primiparous women undergoing vaginal delivery with cephalic presentation at term. Unconditional logistic regression analysis was used to calculate crude and adjusted odds ratios (OR), using 95% confidence intervals (CI). Main exposure was duration of second stage of labor, and main outcome was risks of severe perineal lacerations (third and fourth degree). RESULTS: Risk of severe perineal lacerations increased with duration of second stage of labor. Compared with a second stage of labor of 1 h or less, women with a second stage of more than 2 h had an increased risk (aOR 1.42; 95% CI 1.28-1.58). Compared with non-instrumental vaginal deliveries, the risk was elevated among instrumental vaginal deliveries (aOR 2.24; 95% CI 2.07-2.42). The risk of perineal laceration increased with duration of second stage of labor until less than 3 h in both instrumental and non-instrumental vaginal deliveries, but after 3 h, the ORs did not further increase. After adjustments for potential confounders, macrosomia (birth weight > 4 500 g) and occiput posterior fetal position were risk factors of severe perineal lacerations. CONCLUSIONS: The risk of severe perineal laceration increases with duration until the third hour of second stage of labor. Instrumental delivery is the most significant risk factor for severe lacerations, followed by duration of second stage of labor, fetal size and occiput posterior fetal position.

Trends in Congenital Heart Defects in Infants With Down Syndrome.

BACKGROUND: As a result of antenatal screening, abortion of fetuses with Down syndrome has become increasingly common. Little is known about the cardiovascular phenotype in infants with Down syndrome born today. METHODS: Population-based cohort study based on national health registers including 2588 infants with Down syndrome, live-born in Sweden from 1992 to 2012. Risk ratios for congenital heart defects were calculated per 3-year period, adjusted for maternal age, parity, BMI, smoking, diabetes and hypertensive disease, and infant gender. RESULTS: Any congenital heart defect was diagnosed in 54% of infants with Down syndrome. Overall, year of birth was not associated with risk of any congenital heart defect. However, the risk of complex congenital heart defects decreased over time. Compared with 1992 to 1994, the risk in 2010 to 2012 was reduced by almost 40% (adjusted risk ratio 0.62, 95% confidence interval 0.48-0.79). In contrast, risks for isolated ventricular septal defect (VSD) or atrial septal defect showed significant increases during latter years. Overall, the 3 most common diagnoses were atrioventricular septal defect, VSD, or atrial septal defect, accounting for 42%, 22%, and 16% of congenital heart defects, respectively. Although atrioventricular septal defect was far more common than VSD in 1992 to 1994, they were equally common in 2010 to 2012. CONCLUSIONS: Complex congenital heart defects have become less common in infants diagnosed with Down syndrome. This phenotypic shift could be a result of selective abortion of fetuses with Down syndrome, or due to general improvements in antenatal diagnostics of complex congenital heart defects.

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.

Pregnancy characteristics and maternal risk of breast cancer.

CONTEXT: During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE: To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING: Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS: Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS: Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.

Pulmonary embolism and stroke in relation to pregnancy: how can high-risk women be identified?

OBJECTIVE: Risks of circulatory diseases are increased substantially during late pregnancy and around the time of delivery. This study was undertaken to determine whether preeclampsia, multiple pregnancy, or cesarean delivery account for the majority of pregnancy-related risks of pulmonary embolism and stroke (caused by hemorrhage, infarction, and intracranial venous thrombosis). STUDY DESIGN: We analyzed a population-based cohort of 1,003,489 deliveries in Sweden. Relative risks of pulmonary embolism and stroke were modeled by use of Poisson regression. RESULTS: Preeclampsia was associated with 3- to 12-fold increases in risks of pulmonary embolism and stroke during late pregnancy, at delivery, and in the puerperium, and similar increases in risks were also observed for multiple pregnancies and cesarean delivery. These strong associations could not explain the overall pregnancy-related risks of pulmonary embolism and stroke. CONCLUSION: Preeclampsia, multiple birth, and cesarean delivery are important risk factors for pulmonary embolism and stroke, but they do not account for the majority of the excess risks associated with pregnancy.