Predictive factors in pregnancies with reduced fetal movements: a pilot study.

BACKGROUND: Pregnancies with reduced fetal movements (RFM) are at risk for poor neonatal outcomes and stillbirth. AIM: To investigate whether Doppler measurements or angiogenic factors are good predictors of adverse neonatal outcomes in pregnancies with RFM. METHODS: This is a prospective pilot cohort study of 3243 women seeking care for RFM. Standard care was carried out in all cases. An extra Doppler examination was performed in 128 women to assess the flow in the middle cerebral artery, the umbilical artery, and the uterine artery. In 62/128 pregnancies, a maternal blood sample was obtained for angiogenic and antiangiogenic factors. The composite neonatal outcome of the study was one or more of the following factors: Apgar score <7 at 5', arterial aPh in the umbilical cord ≤7.1, transfer to Neonatal Intensive Care (NICU), stillbirth, and small for gestational age (SGA). RESULTS: In 14.1% (18/128) of the Doppler group and 11.7% (365/3115) of the standard care group, there was an adverse neonatal outcome (p = .51). A higher intervention rate was found in the Doppler group (28% vs. 5.4%, p < .01). The predictive model of adverse neonatal outcomes in women with RFM with angiogenic factors was 0.73 (95% CI 0.54-0.92). The area under the curve improved to 0.89 (CI 95% 0.81-0.97) when parity was added to the model. CONCLUSION: Angiogenic factors may have a place in the prediction of the neonatal outcome of RFM pregnancies. The prediction model's capacity was driven by parity. The obstetrical intervention rate increased with additional Doppler examinations.

Stillbirth in term and late term gestations in Stockholm during a 20-year period, incidence and causes.

INTRODUCTION: The incidence of stillbirth has decreased marginally or remained stable during the past decades in high income countries. A recent report has shown Stockholm to have a lower incidence of stillbirth at term than other parts of Sweden. The risk of antepartum stillbirth increases in late term and postterm pregnancies which is one of the factors contributing to the current discussion regarding the optimal time of induction of labor due to postterm pregnancy. MATERIAL AND METHODS: This is a cohort study based on the Stockholm Stillbirth Database which contains all cases of stillbirth from 1998-2018 in Stockholm County. All cases were reviewed systematically and the cause of death was evaluated according to the Stockholm Stillbirth Classification. Stillbirths diagnosed between gestational week (GW) 37+0 and 40+6 n = 605 were compared to stillbirths diagnosed from GW 41+0 and onwards n = 157, according to the cause of stillbirth and pregnancy and maternal characteristics. The aim was to evaluate the incidence of stillbirth over time and the incidence of stillbirth diagnosed from GW 41+0. RESULTS: In Stockholm County the overall incidence of stillbirth has decreased from 4.6/1000 births during the period 1998-2004 to 3.4/1000 births during the period 2014-2018, p-value <0.001. When comparing the same time periods, the incidence of stillbirth diagnosed from GW 41+0 and onwards has decreased from 0.5/1000 births to 0.15/1000 births, p-value <0.001. Among women still pregnant at GW 41+0 the incidence of stillbirth has decreased from 1.8/ 1000 to 0.5/ 1000. When comparing stillbirths diagnosed at GW 37+0-40+6 with stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of stillbirth in the latter group. CONCLUSION: In Stockholm County there was a decreasing incidence of stillbirth overall and in stillbirths diagnosed from 41+0 weeks of gestation and onwards during the period 1998-2018. In stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of death compared to stillbirths diagnosed between GW 37+0 and 40+6.

Risk factors for poor neonatal outcome in pregnancies with decreased fetal movements.

INTRODUCTION: The incidence of Swedish stillbirths has varied little in the past 40 years, with a reported frequency of 400-450 stillbirths/y (approximately 4‰), despite increased information about fetal movement in the media and awareness among healthcare providers. The objectives of this project were to describe the outcome of pregnancies with reduced fetal movement in a Swedish context and to investigate factors associated with poor neonatal outcome in this group. MATERIAL AND METHODS: A retrospective cohort study was performed at Soder Hospital, Stockholm, Sweden. All single pregnancies at the hospital from January 2016 to December 2017 presenting with reduced fetal movement after 22 gestational weeks were included in the study. A composite neonatal outcome was constructed: 5-minute Apgar score ≤7, arterial pH in the umbilical cord ≤7.10, transfer to neonatal care unit for further care or intrauterine fetal death. RESULTS: For women seeking care for reduced fetal movement, the occurrence of composite poor neonatal outcome ranged from 6.2% to 18.4% within different groups. The highest risk for poor neonatal outcome (18.4%) was found in the group of women with a small-for-gestational-age fetus. Another high-risk group (12.8%) was the one comprising women with normal birthweight/large-for-gestational-age fetuses with an in vitro fertilization pregnancy. CONCLUSIONS: The highest incidence of poor neonatal outcome among women with reduced fetal movement was found in the groups with small-for-gestational-age fetuses in nulliparous and multiparous women. A routine ultrasound assessment for fetal growth in third trimester is supposedly most efficient to identify undiagnosed small for gestational age.

Three Sisters With Heterozygous Gene Variants of CYP24A1: Maternal Hypercalcemia, New-Onset Hypertension, and Neonatal Hypoglycemia.

Gene variants of CYP24A1, which encodes the enzyme 24-hydroxylase, are a most unusual cause of maternal hypercalcemia. Loss-of-function mutations in CYP24A1 result in impaired dehydroxylation of active vitamin D (calcitriol). Secondary to this hypercalcemia, hypercalciuria and suppressed parathyroid hormone (P-PTH) can develop. These gene-variants are most often detected in children exposed to vitamin D prophylaxis. These children develop failure to thrive, hypercalciuria, hypercalcemia, and low PTH levels. CYP24A1 variants have also been reported in adults with hypercalcemia and recurrent urolithiasis. This report describes gestational hypercalcemia in two of three sisters with combined CYP24A1 heterozygous variants. METHODS: We retrospectively investigated medical files, clinical information, and calcium levels during and after pregnancy in three sisters giving birth to nine children. All three sisters were also tested genetically. RESULTS: Two sisters developed hypercalcemia during all seven pregnancies and late-onset hypertension during pregnancy. These sisters had two heterozygote variants in the enzyme CYP24A1: c1186C>T and c443T>C. A third sister had the c1186C>T variant and was normocalcemic. Of the seven children born to the two sisters with combined variants, four had hypercalcemia and five had hypoglycemia as neonates. In these mothers, calcium levels slowly normalized postpartum. In the affected neonates, calcium and blood glucose levels became normal within weeks. CONCLUSION: Combined variants of CYP24A1 caused long-standing gestational hypercalcemia and late-onset hypertension. In neonates, elevated serum calcium and hypoglycemia can be consequences necessitating prompt measures. CYP24A1 mutations should be considered in unexplained gestational hypercalcemia. Their combined effects during pregnancy have not been observed previously.

Mothers' attitudes towards perinatal autopsy after stillbirth.

We investigated mothers' attitudes to autopsy of their stillborn baby and their experiences concerning information and treatment in relation to their loss in an observational study. Data were collected by postal questionnaires and telephone calls. Fifty-four of 72 mothers (76%) replied. Fifty-one (94%) received information from a physician about the possibility of having an autopsy; three (6%) did not get any information. The autopsy rate was 83% (n= 45). Thirty-six of 45 (80%) received adequate information about results. Twenty-five (56%) were pleased with how results were presented. Eleven (24%) were positive about individual contact with the pathologist who performed the autopsy. Fifty-one (94%) stated that their decision concerning autopsy was right. Mothers do not regret their decision concerning perinatal autopsy but they do not always receive thorough and timely information concerning autopsy and its results. Personal contact with the perinatal pathologist might help with specific questions both before and after autopsy.

The Stockholm classification of stillbirth.

OBJECTIVE: To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death. DESIGN: Descriptive. SETTING: All delivery wards in Stockholm. POPULATION: Stillbirths from 22 completed weeks in Stockholm, Sweden. METHODS: Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated. MAIN OUTCOME MEASURE: The classification and the results of the validation are presented. RESULT: The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa=0.70). CONCLUSIONS: The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death.

Correlation between ultrasound and autopsy findings after 2nd trimester terminations of pregnancy.

OBJECTIVE: To compare ultrasound (US) and fetal autopsy findings in 2(nd) trimester termination of pregnancy because of structural fetal anomalies. METHODS: A total of 112 terminations of pregnancy (TOP) between 1999-2003 were reviewed retrospectively. The cases originated from a secondary and a tertiary Fetal Medicine unit in the south Stockholm area, using a common specialized perinatal pathology service. Karyotype was not known at the time of US examination. The findings were compared and classified into four groups according to the degree of agreement between US and autopsy. RESULTS: In 45% of cases there was total agreement between US and autopsy. In 40%, autopsy confirmed all US findings but provided additional information of clinical importance. Partial or total lack of agreement was noted in 11% and 4% of the cases, respectively. Areas of discrepancy involved mainly CNS- and cardiovascular abnormalities and, to a lesser extent, renal anomalies, abdominal wall defects and hydrops/hygroma. Regarding CNS abnormalities the overall rate of agreement was 62%; it was highest in acrania/anencephaly (92%) and lowest in hydrocephaly (39%). CONCLUSION: We find an overall high degree of agreement between US and autopsy findings. Autopsy often provided additional information of clinical value and it should always follow US examination and TOP. Fixation of CNS is crucial for optimal results. Specific limitations of autopsy, i.e., detection of CNS abnormalities, may be reduced by complementary imaging techniques, such as MRI. The ability of US to detect cardiac anomalies is enhanced with the close contact to specialized fetal cardiology.

Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies.

OBJECTIVE: To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. DESIGN: Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. SETTING: Cases were identified through fetal autopsy reports. SUBJECTS: Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. MAIN OUTCOME MEASURES: The findings at the last ultrasound examination were compared with the autopsy reports. RESULTS: In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. CONCLUSION: Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.

Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs.

AIM: To study the risk for complications during pregnancy, delivery, and neonatal period after the use of antiepileptic drugs (AEDs) during pregnancy. METHODS: Women treated with AEDs during pregnancy and with singleton deliveries were identified from the Swedish Medical Birth Registry during the period July 1 1995 to and including 2001 (n = 1350). Risk estimates were made using the Mantel-Haenszel procedure and comparisons with all singleton births in Sweden during this period (n = 559,491). Stratification was made for year of birth, maternal age, parity, and smoking habits. RESULTS: Most of the women (n = 1207, 89%) used AEDs in monotherapy. Carbamazepine was the most commonly used drug (n = 683), followed by valproic acid (n = 255). The rate of caesarean sections was significantly increased (OR = 1.64, 95% CI 1.43-1.89), but it was not possible to differentiate between elective and emergency sections. The risk for pre-eclampsia (OR = 1.66, 95% CI 1.32-2.08) and for hemorrhage after vaginal delivery was increased (OR = 1.29, 95% CI 1.02-1.63). The neonates showed an increased risk for respiratory distress (OR = 2.06, 95% CI 1.62-2.63). CONCLUSION: The study demonstrates a slightly increased risk only for preeclampsia, vaginal hemorrhage after delivery, and respiratory distress in the newborn after the use of AEDs during pregnancy.

Perceived pain and self-estimated activity limitations in women with back pain post-partum.

BACKGROUND AND PURPOSE: In the general population many daily activities have an impact on low back pain. The aim of the present study was to describe pain intensity, localization, type of sensation and perceived activity limitation in women with different back pain patterns post-partum. METHOD: In this cross-sectional survey 119 women with back pain persisting for two months after having given birth were interviewed and examined on average 7.2 months (range 6-10 months) post-partum. Based on pain provocation tests, four different back pain pattern groups were identified. Pain could be provoked in the area of the posterior pelvic/sacroiliac joints, in the lumbar spine, both in the posterior pelvic/sacroiliac joints and in the lumbar spine, and in none of the above areas. All women rated pain intensity on a visual analogue scale (VAS, 0-100 mm), and the pain localization and type of sensation were indicated on a pain drawing. They scored their activity limitations by use of the Disability Rating Index (DRI), which covers 12 daily activity items (VAS, 0-100 mm). RESULTS: There was no significant difference (p = 0.12) in pain intensity (range of medians 19.5-10 mm) between the four groups. However, on average, most areas in the lower back (median 5 mm (range 2-14 mm)), were marked in the group with pain in both the posterior pelvic/sacroiliac joints and in the lumbar spine. The women in the three groups where pain was provoked in the lower area of the back had significantly (p < 0.01) more difficulties with movement-related daily activities than the group where no pain could be provoked. CONCLUSIONS: The findings of this descriptive study suggest that back pain post-partum provoked by clinical tests considerably hampers movement-related activities. It seems important to pay special attention to the women where pain could be provoked in the lower back areas. The women should be identified early in the post-partum period to initiate adequate treatment.