Unveiling sex bias and adverse neonatal outcomes in ultrasound estimation of gestational age: A population-based cohort study.

BACKGROUND: Gestational age estimation by second-trimester ultrasound biometry introduces systematic errors due to sex differences in early foetal growth, consequently increasing the risk of adverse neonatal outcomes. Ultrasound estimation earlier in pregnancy may reduce this bias. OBJECTIVES: To investigate the distribution of sex ratio by gestational age and estimate the risk of adverse outcomes in male foetuses born early-term and female foetuses born post-term by first- and second-trimester ultrasound estimations. METHODS: This population-based study compared two cohorts of births with gestational age based on first- and second-trimester ultrasound in the Medical Birth Registry of Norway between 2016 and 2020. We used a log-binomial regression model to estimate adjusted relative risk (RR) with 95% confidence interval (CI) for Apgar score <7 at 5 min, umbilical artery pH <7.05, neonatal intensive care unit (NICU) admission and respiratory morbidity in relation to foetal sex. RESULTS: The sex ratio at birth in gestational weeks 36-43 showed less male predominance in pregnancies estimated in first compared to second trimester. Any adverse outcome was registered in 627 of 4470 male infants born in gestational weeks 37-38 and 618 of 6406 females born ≥41 weeks. Male infants born in weeks 37-38 had lower risk of NICU admission (RR 0.76, 95% CI 0.58, 0.99), Apgar score <7 at 5 min (RR 0.63, 95% CI 0.28, 1.41) and respiratory morbidity (RR 0.68, 95% CI 0.37, 1.25) in first- compared to second-trimester estimations. Female infants estimated in first trimester born ≥41 weeks had lower risk of umbilical artery pH <7.05, NICU admissions and respiratory morbidity; however, CIs were wide. CONCLUSIONS: Early ultrasound estimation of gestational age may reduce the excess risk of adverse neonatal outcomes and highlight the role of foetal sex and the timing of ultrasound assessment in the clinical evaluation of preterm and post-term pregnancies.

Paternal and maternal birthweight and offspring risk of macrosomia at term gestations: A nationwide population study.

BACKGROUND: There is a paucity of data on whether parents' macrosomia (birthweight ≥4500 g) status influences the risk of macrosomia in the offspring. The role of maternal overweight in the generational effect of macrosomia is not known. OBJECTIVE: To estimate the risk of macrosomia by parental birthweight at term and evaluate if this risk varied with maternal body mass index (BMI, kg/m2) early in pregnancy. METHODS: We used data from the Medical Birth Registry of Norway on all singleton term births (37-42 gestational weeks) during 1967-2017. The primary exposure was parental macrosomia, and the outcome was macrosomia in the second generation. The secondary exposure was maternal BMI. We used binomial regression to calculate relative risk (RR) with a 95% confidence interval. We assessed potential unmeasured confounding and selection bias using a probabilistic bias analysis and performed analyses with and without imputation for variables with missing values. RESULTS: The data included 647,957 singleton parent-offspring trios born at term. The prevalence of macrosomia was 3.2% (n = 41,396) in the parental generation and 4.0% (n = 25,673) in the offspring generation. Macrosomia in parents was associated with an increased risk of macrosomia in offspring, with the RR for both parents were born macrosomic being 6.53 (95% confidence interval [CI] 5.31, 8.05), only mother macrosomic 3.37 (95% CI 3.17, 3.57) and only father macrosomic RR 2.22 (95% CI 2.12, 2.33). These risks increased by maternal BMI in early pregnancy: if both parents were born macrosomic, 17% of infants were macrosomic among mothers with normal BMI. If both parents were macrosomic and the mothers were obese, 31% of offspring were macrosomic. Macrosomia-related adverse outcomes did not differ with parental macrosomia status. CONCLUSIONS: Parents' weight at birth and maternal BMI appear to be strongly associated with macrosomia in the offspring delivered at term gestations.

Shoulder dystocia by severity in families: A nationwide population study.

INTRODUCTION: Previous studies have established a history of shoulder dystocia as an important risk factor for shoulder dystocia, but studies on shoulder dystocia by severity are scarce. It is unknown if shoulder dystocia tends to be passed on between generations. We aimed to assess the recurrence risk of shoulder dystocia by severity in the same woman and between generations on both the maternal and paternal side. We also assessed the likelihood of a second delivery and planned cesarean section after shoulder dystocia. MATERIAL AND METHODS: This was a population-based cohort study, using data from the Medical Birth Registry of Norway. To study recurrence in the same mother, we identified 1 091 067 pairs of first and second, second and third, and third and fourth births in the same mother. To study intergenerational recurrence, we identified an individual both as a newborn and as a mother or father in 824 323 mother-offspring pairs and 614 663 father-offspring pairs. We used Bayesian log-binomial multilevel regression to calculate relative risks (RR) with 95% credible intervals. RESULTS: In subsequent deliveries in the same woman the unadjusted RR of recurrence was 7.05 (95% credible interval 6.39-7.79) and 2.99 (2.71-3.31) after adjusting for possible confounders, including current birthweight. The RRs were higher with severe shoulder dystocia as exposure or outcome. With severe shoulder dystocia as both exposure and outcome, unadjusted and adjusted RR was 20.42 (14.25-29.26) and 6.29 (4.41-8.99), respectively. Women with severe and mild shoulder dystocia and those without had subsequent delivery rates of 71.1, 68.9 and 69.0%, respectively. However, the rates of planned cesarean section in subsequent deliveries for those without shoulder dystocia, mild and severe were 1.3, 5.2 and 16.0%, respectively. On the maternal side the unadjusted inter-generational RR of recurrence was 2.82 (2.25-3.54) and 1.41 (1.05-1.90) on the paternal side. Corresponding adjusted RRs were 1.90 (1.51-2.40) and 1.19 (0.88-1.61), respectively. CONCLUSIONS: We found a strong recurrence risk of shoulder dystocia, especially severe, in subsequent deliveries in the same woman. The inter-generational recurrence risk was higher on the maternal than paternal side. Women with a history of shoulder dystocia had more often planned cesarean section.

Placental pathology and neonatal morbidity: exploring the impact of gestational age at birth.

AIM: To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome. METHODS: This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis. RESULTS: Late-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA. CONCLUSIONS: HCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention.

Increasing region of interest width reduces neonatal circumferential strain.

OBJECTIVE: There is growing interest in speckle tracking echocardiography-derived strain as a measure of left ventricular function in neonates. However, knowledge gaps remain regarding the effect of image acquisition and processing parameters on circumferential strain measurements. The aim of this study was to evaluate the effect of using different region of interest (ROI) widths on speckle tracking derived circumferential strain in healthy neonates. METHODS: Thirty healthy-term-born neonates were examined with speckle-tracking echocardiography in the short-axis view. Circumferential strain values were acquired and compared using two different ROI widths. Furthermore, strain values in the different vendor-defined wall layers were also compared. RESULTS: Increasing ROI width led to a decrease in global circumferential strain (GCS) in the midwall and epicardial layers, the respective decreases in strain being -23.4 ± .6% to -22.0 ± 1.1%, p < .0001 and 18.5 ± 1.7% to -15.6 ± 2.0%, p < .0001. Segmental analyses were consistent with these results, apart from two segments in the midwall. There was no statistically significant effect on strain for the endocardial layer. A gradient was seen where strain increased from the epicardial to endocardial layers. CONCLUSION: Increasing ROI width led to a decrease in GCS in the midwall and epicardium. There is an increase in circumferential strain when moving from the epicardial toward the endocardial layer. Clinicians wishing to implement circumferential strain into their practice should consider ROI width variation as a potential confounder in their measurements.

Use of non-governmental maternity services and pregnancy outcomes among undocumented women: a cohort study from Norway.

BACKGROUND: In 2011 Norway granted undocumented women the right to antenatal care and to give birth at a hospital but did not include them in the general practitioner and reimbursement schemes. As a response to limited access to health care, Non-Governmental Organizations (NGO) have been running health clinics for undocumented migrants in Norway's two largest cities. To further facilitate universal health coverage, there is a need to investigate how pregnant undocumented women use NGO clinics and how this affects their maternal health. We therefore investigated the care received, occurrence of pregnancy-related complications and pregnancy outcomes in women receiving antenatal care at these clinics. METHODS: In this historic cohort study we included pregnant women aged 18-49 attending urban NGO clinics from 2009 to 2020 and retrieved their medical records from referral hospitals. We compared women based on region of origin using log-binominal regression to estimate relative risk of adverse pregnancy outcomes. RESULTS: We identified 582 pregnancies in 500 women during the study period. About half (46.5%) the women sought antenatal care after gestational week 12, and 25.7% after week 22. The women had median 1 (IQR 1-3) antenatal visit at the NGO clinics, which referred 77.7% of the women to public health care. A total of 28.4% of women were referred for induced abortion. In 205 retrieved deliveries in medical records, there was a 45.9% risk for any adverse pregnancy outcome. The risk of stillbirth was 1.0%, preterm birth 10.3%, and emergency caesarean section 19.3%. CONCLUSION: Pregnant undocumented women who use NGO clinics receive substandard antenatal care and have a high risk of adverse pregnancy outcomes despite low occurrence of comorbidities. To achieve universal health coverage, increased attention should be given to the structural vulnerabilities of undocumented women and to ensure that adequate antenatal care is accessible for them.

Placental histology predicted adverse outcomes in extremely premature neonates in Norway-population-based study.

AIM: We evaluated the role of placental pathology in predicting adverse outcomes for neonates born extremely preterm (EPT) before 28 weeks of gestation. METHODS: This was a prospective observational study of 123 extremely preterm singletons born in a hospital in western Norway, and the placentas were classified according to the Amsterdam criteria. The associations between histologic chorioamnionitis (HCA), by the presence or the absence of a foetal inflammatory response (FIR+ or FIR-), maternal vascular malperfusion (MVM) as a whole and adverse neonatal outcomes were evaluated by logistic regression analyses. Adverse outcomes were defined as perinatal death, necrotising enterocolitis (NEC), bronchopulmonary dysplasia (BPD), brain pathology by magnetic resonance imaging at term-equivalent age, retinopathy of prematurity and early-onset neonatal sepsis. The results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: HCA was associated with NEC (OR 12.2, 95% CI 1.1 to 137.1). HCA/FIR+ was associated with BPD (OR 14.9, 95% CI 1.8-122.3) and brain pathology (OR 9.8, 95% CI 1.4-71.6), but HCA/FIR- was not. The only neonatal outcome that MVM was associated with was low birthweight. CONCLUSION: Placental histology provided important information when assessing the risk of adverse neonatal outcomes following EPT birth.

Recurrence of postpartum hemorrhage, maternal and paternal contribution, and the effect of offspring birthweight and sex: a population-based cohort study.

PURPOSE: This study examines individual aggregation of postpartum hemorrhage (PPH), paternal contribution and how offspring birthweight and sex influence recurrence of PPH. Further, we wanted to estimate the proportion of PPH cases attributable to a history of PPH or current birthweight. METHODS: We studied all singleton births in Norway from 1967 to 2017 using data from Norwegian medical and administrational registries. Subsequent births in the parents were linked. Multilevel logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PPH defined as blood loss > 500 ml, blood loss > 1500 ml, or the need for blood transfusion in parous women. Main exposures were previous PPH, high birthweight, and fetal sex. We calculated adjusted population attributable fractions for previous PPH and current high birthweight. RESULTS: Mothers with a history of PPH had three- and sixfold higher risks of PPH in their second and third deliveries, respectively (adjusted OR 2.9; 95% CI 2.9-3.0 and 6.0; 5.5-6.6). Severe PPH (> 1500 ml) had the highest risk of recurrence. The paternal contribution to recurrence of PPH in deliveries with two different mothers was weak, but significant. If the neonate was male, the risk of PPH was reduced. A history of PPH or birthweight ≥ 4000 g each accounted for 15% of the total number of PPH cases. CONCLUSION: A history of PPH and current birthweight exerted strong effects at both the individual and population levels. Recurrence risk was highest for severe PPH. Occurrence and recurrence were lower in male fetuses, and the paternal influence was weak.

Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes.

Recurrence of postpartum hemorrhage in relatives: A population-based cohort study.

INTRODUCTION: Studies on the family aggregation of postpartum hemorrhage (PPH) are scarce and with inconsistent results, and to what extent current birthweight influences recurrence between relatives remains to be studied. Further, family aggregation of PPH has been studied from an individual, but not from a public heath perspective. We aimed to investigate family aggregation of PPH in Norway, how birthweight influences these effects, and to estimate the proportion of PPH cases attributable to a family history of PPH and current birthweight. MATERIAL AND METHODS: Using data from the Medical Birth Registry of Norway, Statistics Norway, and Central Population Registry of Norway we identified individuals as newborns, parents, grandparents, and full and half-siblings, and studied 1 002 687 mother-offspring, 841 164 father-offspring, and 761 011 both-parents-offspring pairs. We used multilevel logistic regression to calculate odds ratios (OR) with 95% CI. RESULTS: If the birth of the mother but not of the father involved PPH, then the OR of PPH (>500 mL) in the next generation was 1.44 (95% CI 1.39-1.49). If the birth of the father but not of the mother involved PPH, then OR was 1.12 (95% CI 1.08-1.16). These effects were stronger in severe PPH. Recurrence between siblings was highest between full sisters (OR 1.47, 95% CI 1.41-1.52), followed by maternal half-sisters, paternal half-sisters, and partners of full brothers. A family history of PPH or birthweight of 4000 g or more accounted for ≤5% and 15% of the total number of PPH cases, respectively. CONCLUSIONS: A history of PPH in relatives influenced the recurrence risk of PPH in a dose-response pattern consistent with the anticipated proportion of shared genes. The recurrence was highest through the maternal line.

Isolated single umbilical artery and the risk of adverse perinatal outcome and third stage of labor complications: A population-based study.

INTRODUCTION: Isolated single umbilical artery (iSUA) refers to single umbilical artery cords with no other fetal malformations. The association of iSUA to adverse outcome of pregnancy has not been consistently reported, and whether iSUA carries increased risk of third stage of labor complications has not been studied. We aimed to investigate the risk of adverse perinatal outcome, third stage of labor complications, and associated placental and cord characteristics in pregnancies with iSUA. A further aim was to assess the risk of recurrence of iSUA and anomalous cord or placenta characteristics in Norway. MATERIAL AND METHODS: This was a population-based study of all singleton pregnancies with gestational age >16 weeks at birth using data from the Medical Birth Registry of Norway from 1999 to 2014 (n = 918 933). Odds ratios (OR) with 95% confidence intervals were calculated for adverse perinatal outcome (preterm birth, perinatal and intrauterine death, low Apgar score, transferral to neonatal intensive care ward, placental and cord characteristics [placental weight, cord length and knots, anomalous cord insertion, placental abruption and previa]), and third stage of labor complications (postpartum hemorrhage and the need for manual placental removal or curettage) in pregnancies with iSUA, and recurrence of iSUA using generalized estimating equations and logistic regression. RESULTS: Pregnancies with iSUA carried increased risk of adverse perinatal outcome (OR 5.06, 95% confidence interval [CI] 4.26-6.02) and perinatal and intrauterine death (OR 5.62, 95% CI 4.69-6.73), and a 73% and 55% increased risk of preterm birth and small-for-gestational-age neonate, respectively. The presence of iSUA also carried increased risk of a small placenta, placenta previa and abruption, anomalous cord insertion, long cord, cord knot and third stage of labor complications. Women with iSUA, long cord or anomalous cord insertion in one pregnancy carried increased risk of iSUA in the subsequent pregnancy. CONCLUSIONS: The presence of ISUA was associated with a more than five times increased risk of intrauterine and perinatal death and with placental and cord complications. The high associated risk of adverse outcome justifies follow up with assessment of fetal wellbeing in the third trimester, intrapartum surveillance and preparedness for third stage of labor complications.

An immunocompromised woman in her twenties with abdominal pain and vaginal discharge. / Immunsupprimert kvinne i 20-årene med magesmerter og utflod.

BACKGROUND: Women of reproductive age who present with abdominal pain and purulent vaginal discharge are commonly seen in primary health care and gynaecological outpatient clinics. Their symptoms are often caused by sexually transmitted infections and efficiently treated with empiric antibiotics. However, in some cases diagnostics are more challenging. CASE PRESENTATION: We present the case history of a woman in her twenties with multiple sclerosis under rituximab treatment. She presented with a wide range of symptoms over twelve months, including upper and lower respiratory tract infections, urinary bladder urgency, chronic abdominal pain, diarrhoea, bloody stools, weight loss and fatigue. She underwent urological and gastroenterological examinations which yielded normal findings. After the onset of genital discomfort and copious amounts of vaginal discharge, gynaecological examination and routine microbiological testing of discharge were negative. Finally, she presented with septicaemia and progressive abdominal pain. Laparoscopy was performed due to absence of recovery after initial transvaginal ultrasound-guided aspiration of ovarian cysts. The microbe Ureaplasma urealyticum was detected in ovarian pus. Treatment with doxycycline resulted in full recovery. INTERPRETATION: It is important to consider opportunistic microbes in immunocompromised patients, as they might pose a major diagnostic challenge and require the involvement of several specialties.

Estimated date of delivery based on second trimester fetal head circumference: A population-based validation of 21 451 deliveries.

INTRODUCTION: Fetal biometry is used for determining gestational age and estimated date of delivery (EDD). However, the accuracy of the EDD depends on the assumed length of pregnancy included in the calculation. This study aimed at assessing the actual pregnancy length and accuracy of EDD prediction based on fetal head circumference measured at the second trimester. MATERIAL AND METHODS: This was a population-based observational study with the following inclusion criteria: singleton pregnancy, head circumference dating in the second trimester, spontaneous onset or induction of delivery ≥ 294 days of gestation, live birth. The EDD was set anticipating a pregnancy length of 282 days. Bias in the prediction of EDD was defined as the difference between the actual date of birth and the EDD. RESULTS: Head circumference measurements were available for 21 451 pregnancies. Ultrasound-dated pregnancies had a median pregnancy length of 283.03 days, corresponding to a method bias of 1.03 days (95% CI; 0.89-1.16). This bias was dependent on the head circumference at dating, ranging from -1.58 days (95% CI; -3.54 to 1.12) to 3.42 days (95% CI; 1.98-4.31). The median pregnancy length, based on the last menstrual period of women with a regular menstrual cycle (n = 12 985), was 283.15 days (95% CI; 282.91-283.31). A total of 5685 (22.9%, 95% CI; 22.4% to 23.4%) and 886 women (3.6%, 95% CI; 3.3%-3.8%) were still pregnant 7 and 14 days after the EDD, respectively. CONCLUSIONS: Second trimester head circumference measurements can be safely used to predict EDD. A revision of the pregnancy length to 283 days will reduce the bias of EDD prediction to a level comparable with other methods.

Maternal diabetes alters the development of ductus venosus shunting in the fetus.

INTRODUCTION: Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous distribution, including increased ductus venosus shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on umbilical venous and ductus venosus flow is not known. MATERIAL AND METHODS: In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the umbilical vein and ductus venosus were used for calculating blood flow volumes. The development of the umbilical venous flow, ductus venosus flow and ductus venosus shunt fraction (% of umbilical venous blood shunted through the ductus venosus) was compared with a reference population, and the effect of HbA1c on the ductus venosus flow was assessed. RESULTS: The umbilical venous flow was larger in pregnancies with pregestational diabetes mellitus than in low-risk pregnancies (p < 0.001) but smaller when normalized for fetal weight (p = 0.036). The distributional pattern of the ductus venosus flow developed differently in diabetic pregnancies, particularly during the third trimester, being smaller (p = 0.007), also when normalized for fetal weight (p < 0.001). Correspondingly, the ductus venosus shunt fraction was reduced (p < 0.0001), most prominently at 36 weeks. There were negative relations between the maternal HbA1c and the ductus venosus flow velocity, flow volume and shunt fraction. CONCLUSIONS: In pregnancies with pregestational diabetes mellitus, prioritized umbilical venous distribution to the fetal liver and lower ductus venosus shunt capacity reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth.

Risk factors for recurrence of hypertensive disorders of pregnancy, a population-based cohort study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) tend to recur from one pregnancy to the next. The aims of the study were to assess the recurrence risk according to type of HDP defined by gestational age at birth and to examine whether recurrence is associated with the following additional risk factors for HDP: maternal age, smoking, inter-delivery interval, diabetes, body mass index, and fetal growth restriction, and to assess temporal trends in these associations. MATERIAL AND METHODS: All women with two singleton births in the Medical Birth Registry of Norway 1967-2012 (n = 742 980) were included in this population-based cohort study. Logistic regression was used to calculate odds ratios for the risk of recurrent HDP according to type of HDP. RESULTS: The highest odds ratio of recurrence was observed for the same type of HDP based on gestational age at delivery. After gestational hypertension and term preeclampsia, the risk for the same type to recur increased 10-fold, whereas after late and early preterm preeclampsia, the risk increased 27- and 97-fold, respectively. The recurrence of early preterm preeclampsia was less influenced by additional risk factors compared with term HDP. Recurrence of early preterm HDP was significantly lower from 1993 onwards. CONCLUSIONS: Recurrent HDP tended to be of the same type as the previous HDP. Risk of recurrence associated with additional risk factors was observed particularly after term. The odds ratio of recurrence of early preterm HDP was significantly lower from 1993 onwards.

Placenta, cord and membranes: a dual center validation study of midwives' classifications and notifications to the Medical Birth Registry of Norway.

INTRODUCTION: A validation of data regarding the placenta, cord and membranes in Medical Birth Registry of Norway (MBRN) is lacking. Here we investigate the inter- and intra-observer agreement of observations regarding the placenta, cord and membranes to the MBRN in two institutions. MATERIAL AND METHODS: We conducted a dual center validation study of data regarding placenta, cord and membranes. In the inter-observer study, 196 placentas in two institutions were examined by the attending midwife and a blinded colleague, whereas in the intra-observer study registrations by the attending midwife on 195 placentas were compared with her own registrations to the MBRN. In a separate sample consisting of 51 placental pathology reports, midwives' registrations to the MBRN were compared with the pathology report. For categorical and continuous variables, agreement was assessed by kappa value and paired sample t-test, respectively. RESULTS: Inter-observer agreement between two midwives for cord insertion site and bi-placenta, cord knots and vessel anomalies were good (kappa values >0.79 and >0.96, respectively). The inter- and intra-observer study showed no significant differences regarding placental weight and cord length (p = 0.31 and 0.28, p = 0.71 and 0.39, respectively). The inter-observer agreement between the pathology reports and midwives' registrations was good for gross placental and cord variants (kappa 0.73-1.0), but there were significant differences in placental weight and cord length (p < 0.0001). CONCLUSIONS: The results suggest that the validity of data regarding placenta and cord in the MBRN is sufficiently high to justify future large-scale epidemiologic research based on this database.

Velamentous or marginal cord insertion and the risk of spontaneous preterm birth, prelabor rupture of the membranes, and anomalous cord length, a population-based study.

INTRODUCTION: Anomalous cord insertion is associated with increased risk of adverse maternal and perinatal outcome. Our aim was to study whether anomalous cord insertion is associated with prelabor rupture of membranes (PROM), preterm PROM (pPROM), long or short umbilical cord, and time trend of spontaneous preterm birth (SPTB) and anomalous cord insertion. MATERIAL AND METHODS: A population-based register study using data from the Medical Birth Register of Norway including all singleton births (gestational age >16 weeks and <45 weeks) during 1999-2013 (n = 860 465) to calculate odds ratios (ORs) for PROM, pPROM, SPTB, and cord length (>95th or <5th centile) according to the cord insertion site by logistic regression with adjustment for possible confounders. We also assessed time trends of SPTB and anomalous cord insertion. RESULTS: Velamentous insertion of the cord was associated with an increased risk of PROM (OR 1.6, 95% CI 1.5-1.7), pPROM (OR 2.7, 95% CI 2.4-3.0), SPTB (OR 2.0, 95% CI 1.9-2.2), and a short cord (OR 1.7, 95% CI 1.5-1.8). Marginal insertion was to a lesser extent associated with these complications. Occurrences of SPTB and anomalous insertion declined. The decline in SPTB persisted after including an interaction term between anomalous insertion and time. CONCLUSIONS: Velamentous and, to a lesser extent, marginal cord insertions were associated with increased risk of PROM, pPROM, SPTB, and short cord. This suggests a common pathogenesis behind altered function of the membranes, cord, and placenta. The decline in SPTB could not be explained by the reduction in the occurrence of anomalous cord insertion.