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Background and Objectives: To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. Materials and Methods: Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD‐positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD‐positive child and thus after receiving anti‐D at least twice (group A) or during the first pregnancy at risk for immunization (group B). Results: Sixty‐two RhD immunized women with a total of 150 RhD‐positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD‐positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non‐intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody‐dependent cell‐mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD‐positive child (group B), often before they had ever received anti‐D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). Conclusion: RhD‐mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD‐positive child are at highest risk of severe disease in the next pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Lithium use during pregnancy reduces the risk of mood episodes in the perinatal period for women with bipolar disorder. Some previous studies found deleterious effects of intrauterine lithium exposure on birth outcomes, yet little is known about a dose response relationship. The current study investigated the influence of maternal lithium serum levels on birth outcomes. Methods: This retrospective observational cohort study included women with a bipolar spectrum disorder who were referred to a specialized psychiatric and obstetric outpatient clinic from 2003 to 2019 and used lithium during the entire pregnancy. For 101 pregnancies at least one lithium level during pregnancy was available. A weighted average lithium level was calculated for the entire pregnancy, as well as for each trimester. Detailed information on maternal, obstetric and neonatal outcomes were retrieved from the medical records. Linear and logistic regression models were used to investigate the association between weighted average lithium level and pregnancy duration, birth weight percentiles, preterm birth and large for gestational age births (LGA). In subsequent exploratory analyses, we studied the role of thyroid‐stimulating hormone (TSH) and thyroxine (T4) as a mediator in the found associations. Results: The weighted average lithium serum level during pregnancy was negatively associated with pregnancy duration and positively with preterm birth, but not with birth weight percentile or LGA. In exploratory analyses, TSH and T4 did not mediate the association between average lithium serum level and pregnancy duration. Conclusion: The results of this cohort study during pregnancy indicate a dose response relationship between maternal lithium serum levels and pregnancy duration. [ABSTRACT FROM AUTHOR]

Objective: Lithium is often continued during pregnancy to reduce the risk of perinatal mood episodes for women with bipolar disorder. However, little is known about the effect of intrauterine lithium exposure on brain development. The aim of this study was to investigate brain structure in children after intrauterine exposure to lithium. Methods: Participants were offspring, aged 8–14 years, of women with a diagnosis of bipolar spectrum disorder. In total, 63 children participated in the study: 30 with and 33 without intrauterine exposure to lithium. Global brain volume outcomes and white matter integrity were assessed using structural MRI and diffusion tensor imaging, respectively. Primary outcomes were total brain, cortical and subcortical gray matter, cortical white matter, lateral ventricles, cerebellum, hippocampus and amygdala volumes, cortical thickness, cortical surface area and global fractional anisotropy, and mean diffusivity. To assess how our data compared to the general population, global brain volumes were compared to data from the Generation R study (N = 3243). Results: In our primary analyses, we found no statistically significant associations between intrauterine exposure to lithium and structural brain measures. There was a non‐significant trend toward reduced subcortical gray matter volume. Compared to the general population, lithium‐exposed children showed reduced subcortical gray and cortical white matter volumes. Conclusion: We found no differences in brain structure between lithium‐exposed and non‐lithium‐exposed children aged 8–14 years following correction for multiple testing. While a rare population to study, future and likely multi‐site studies with larger datasets are required to validate and extend these initial findings. [ABSTRACT FROM AUTHOR]

Objective: Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long‐term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school‐aged children. Methods: We performed a cross‐sectional neurodevelopmental assessment of 91 children aged 6–14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy. Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report. Results: No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. Conclusions: In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school‐aged children (6–14 years). [ABSTRACT FROM AUTHOR]

Objectives: Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium‐exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium‐exposed children with the aim to provide further knowledge on the long‐term effects of lithium use during pregnancy. Methods: Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6–14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders‐Oomen Nonverbal Intelligence Test and the NEPSY‐II‐NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. Results: Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. Conclusion: In this study, we found no evidence for significantly altered neuropsychological functioning of lithium‐exposed children at the age of 6–14 years, when compared to non‐lithium‐exposed controls. [ABSTRACT FROM AUTHOR]

Abstract Background The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children. Methods/Design We set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion. The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR). All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness. Discussion The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance.

Background: Lithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development. Aims: To investigate the impact of lithium exposure on early fetal growth. Methods: In this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands (n =119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region (n =8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18–22 weeks of gestation. Results: Lithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.53, 3.01), in abdominal circumference of 5.54 mm (95% confidence interval: 3.95, 7.12) and in femur length of 0.59 mm (95% confidence interval: 0.22, 0.96) at 18–22 weeks gestation. Furthermore, lithium use during pregnancy was associated with an average increase in birth weight of 142.43 grams (95% confidence interval: 58.01, 226.89), whereas it was associated with an average decrease of 1.41 weeks in gestational duration (95% confidence interval: −1.78, −1.05). Conclusions: Lithium use during pregnancy was associated with increased fetal growth parameters at 18–22 weeks gestational age and increased birth weight. Further research is needed to evaluate both short- and long-term implications, as well as the mechanisms driving this difference in growth. [ABSTRACT FROM AUTHOR]

Background and objectives: A successful routine RBC alloantibody screening programme should not lead to unnecessary emotional burden during pregnancy due to inadequate counselling on the risk of severe haemolytic disease of the foetus and the newborn (HDFN). Rareness of this disease may result in insufficient knowledge and subsequent inadequate information transfer to women, diagnosed with RBC antibodies. We investigated the current knowledge, views and experiences of Dutch obstetric care providers regarding RBC alloimmunization during pregnancy. Materials and methods: We performed a quantitative cross‐sectional study, using a structured digital questionnaire to measure knowledge, attitude and practices (KAP) regarding maternal RBC alloimmunization among Dutch obstetric care providers in 2016. Results: About 10% of obstetric care providers completed the questionnaire. A sufficient level of knowledge was found in 7% of all participants (N = 329). Knowledge about RhD immunisation and prophylaxis was sufficient in 60% of the responders. Knowledge gaps were found concerning the relevance of non‐RhD RBC antibodies, the indications for giving extra RhD prophylaxis and the interpretation of laboratory test results. Healthcare providers estimated their own level of knowledge 'sufficient' (primary/secondary care) to 'good' (tertiary care), and all participants considered their professional role important within the screening programme. Conclusion: Dutch obstetric care providers showed a lack of knowledge regarding maternal RBC immunization. Awareness of the lack of knowledge is necessary to help obstetric care providers to be careful in giving information and even to decide to contact the expert centre before counselling the patient. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aim to evaluate trends in the condition of fetuses and neonates with hemolytic disease at the time of first intrauterine transfusion (IUT) and at birth, in relation to routine first-trimester antibody screening, referral guidelines, and centralization of fetal therapy.Method: We conducted a 30-year cohort study including all women and fetuses treated with IUT for red cell alloimmunization at the Dutch national referral center for fetal therapy.Results: Six hundred forty-five fetuses received 1852 transfusions between 1 January 1987 and 31 December 2016. After the introduction of routine first-trimester antibody screening, the hydrops rate declined from 39% to 15% (OR 0.284, 95% CI, 0.19-0.42, P < 0.001). In the last time cohort, only one fetus presented with severe hydrops (OR 0.482, 95% CI, 0.38-0.62, P < 0.001). Infants are born less often <32 weeks (OR 0.572, 95% CI, 0.39-0.83, P = 0.004) and with higher neonatal hemoglobin (P < 0.001). Neonatal hemoglobin was positively independently associated with gestational age at birth, fetal hemoglobin, and additional intraperitoneal transfusion at last IUT.Conclusion: Severe alloimmune hydrops, a formerly often lethal condition, has practically disappeared, most likely as a result of the introduction of routine early alloantibody screening, use of national guidelines, and pooling of expertise in national reference laboratories and a referral center for fetal therapy. [ABSTRACT FROM AUTHOR]

BackgroundLithium is challenging to dose during pregnancy.AimsTo provide guidance for dosing lithium during pregnancy.MethodRetrospective observational cohort study. Data on lithium blood level measurements (n = 1101), the daily lithium dose, dosing alterations/frequency and creatinine blood levels were obtained from 113 pregnancies of women receiving lithium treatment during pregnancy and the postpartum period.ResultsLithium blood levels decreased in the first trimester (-24%, 95% CI -15 to -35), reached a nadir in the second trimester (-36%, 95% CI -27 to -47), increased in the third trimester (-21%, 95% CI -13 to -30) and were still slightly increased postpartum (+9%, 95% CI +2 to +15). Delivery itself was not associated with an acute change in lithium and creatinine blood levels.ConclusionsWe recommend close monitoring of lithium blood levels until 34 weeks of pregnancy, then weekly until delivery and twice weekly for the first 2 weeks postpartum. We suggest creatinine blood levels are measured to monitor renal clearance. [ABSTRACT FROM AUTHOR]

Background: Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fy(a), Fy(b), Jk(a), Jk(b), and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported.Study Design and Methods: Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved.Results: A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs.Conclusion: Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens-matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs. [ABSTRACT FROM AUTHOR]

Fetal anemia is a serious complication in pregnancy and associated with perinatal mortality and morbidity. During 25 years of worldwide experience with intravascular intrauterine blood transfusion, a variety of indications have been described. Intrauterine transfusion (IUT) treatment is considered most successful for fetal anemia due to red cell alloimmunization. Moreover, the use of this procedure has also been reported in pregnancies with parvovirus B19 infection, fetomaternal hemorrhage and placental chorioangiomas, for example. This review focuses on the current indications of intrauterine blood transfusions. In addition, we describe the potential complications of IUT treatment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Intravascular intrauterine transfusion (IUT) is an effective and relatively safe method for the treatment of fetal anemia. Although implemented in centers all over the world in the 1980s, the length and strength of the learning curve for this procedure has never been studied. Cumulative sum (CUSUM) analysis has been increasingly used as a graphical and statistical tool for quality control and learning curve assessment in clinical medicine. We aimed to test the feasibility of CUSUM analysis for quality control in fetal therapy by using this method to monitor individual performance of IUT in the learning phase and over the long term. Methods: IUTs performed in the Dutch referral center for fetal therapy from 1987 to 2009 were retrospectively classified as successful or failed. Failed was defined as no net transfusion or the occurrence of life-threatening procedure-related complications. The CUSUM statistical method was used to estimate individual learning curves and to monitor long-term performance. Four operators who each performed at least 200 procedures were included. Results: Individual CUSUM graphs were easily assessed. Both operators pioneering IUT in the late 1980s had long learning phases. The 2 operators learning IUT in later years in an experienced team performed acceptably from the start and reached a level of competence after 34 and 49 procedures. Discussion: CUSUM analysis is a feasible method for quality control in fetal therapy. In an experienced setting, individual competence may be reached after 30 to 50 IUTs. Our data suggest that operators need at least 10 procedures per year to keep a level of competence. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short-and long-term outcome in surviving children. Methods/Design: We set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion. The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR). All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness. Discussion: The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance [ABSTRACT FROM AUTHOR]

A 28-year-old primigravida with severe oligohydramnios and pre-eclamptic symptoms was found to have Cushing's syndrome caused by an adrenocortical tumor. After meternal therapy the amniotic volume normalised, but the fetus succumbed. As clinical features of pre-eclampsia and Cushing's syndrome may overlap, diagnosis can be delayed or even missed. [ABSTRACT FROM AUTHOR]

Background: There is controversy on critical cut-off values of laboratory testing to select pregnancies at increased risk for anti-Kell-mediated hemolytic disease of the fetus and newborn. Without early detection and treatment, anti-Kell-mediated hemolytic disease of the fetus and newborn may result in progressive fetal anemia, fetal hydrops, asphyxia, and perinatal death.Objective: We aimed to determine the value of repeated anti-Kell titer determination and biological activity measurement using the antibody-dependent cellular cytotoxicity test determination in the management of pregnancies at risk for anti-Kell-mediated hemolytic disease of the fetus and newborn.Study Design: This was a retrospective cohort study of pregnancies with anti-Kell and a Kell-positive fetus, identified from January 1999 through April 2015. Laboratory test results and clinical outcome were collected from the Dutch nationwide screening program and the national reference center for fetal therapy in The Netherlands, the Leiden University Medical Center. Diagnostic accuracy was measured (receiver operating characteristic curves, sensitivity, specificity, positive and negative predictive values) for anti-Kell titers and antibody-dependent cellular cytotoxicity test. The relationship between the titer and antibody-dependent cellular cytotoxicity measurements and the 2 foregoing measurements were computed with a Pearson product-moment correlation coefficient.Results: In a 16-year unselected cohort, representing screening results of 3.2 million pregnancies resulting in live births in The Netherlands, we identified 1026 Kell-immunized pregnancies. In all, 93 pregnant women had anti-Kell and a Kell-positive child, without other red cell alloantibodies. In all, 49 children (53%) needed intrauterine or postnatal transfusion therapy. The first anti-Kell titer showed already a high diagnostic accuracy with an area under the curve of 91%. The optimal cut-off point for the titer was 4 (sensitivity 100%; 95% confidence interval, 91-100), specificity 27% (95% confidence interval, 15-43), and positive predictive value 60% (49-71%). The antibody-dependent cellular cytotoxicity test was not informative to select high-risk pregnancies. Linear regression showed no significant change during pregnancy, when antibody titer and antibody-dependent cellular cytotoxicity test results were compared with every 2 foregoing measurements (P < .0001).Conclusion: Early determination of the anti-Kell titer is sufficient to select pregnancies at increased risk for hemolytic disease of the fetus and newborn with need for transfusion therapy. If the Kell status of the fetus is known to be positive, a titer of ≥4 can be used to target intensive clinical monitoring. [ABSTRACT FROM AUTHOR]

Background: Intrauterine transfusion for severe alloimmunization in pregnancy performed <20 weeks' gestation is associated with a higher fetal death rate. Intravenous immunoglobulins may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions.Objective: We evaluated whether maternal treatment with intravenous immunoglobulins defers the development of severe fetal anemia and its consequences in a retrospective cohort to which 12 fetal therapy centers contributed.Study Design: We included consecutive pregnancies of alloimmunized women with a history of severe hemolytic disease and by propensity analysis compared index pregnancies treated with intravenous immunoglobulins (n = 24) with pregnancies managed without intravenous immunoglobulins (n = 28).Results: In index pregnancies with intravenous immunoglobulin treatment, fetal anemia developed on average 15 days later compared to previous pregnancies (8% less often <20 weeks' gestation). In pregnancies without intravenous immunoglobulin treatment anemia developed 9 days earlier compared to previous pregnancies (10% more <20 weeks), an adjusted 4-day between-group difference in favor of the immunoglobulin group (95% confidence interval, -10 to +18; P = .564). In the subcohort in which immunoglobulin treatment was started <13 weeks, anemia developed 25 days later and 31% less <20 weeks' gestation (54% compared to 23%) than in the previous pregnancy. Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (odds ratio, 0.03; 95% confidence interval, 0-0.5; P = .011). Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (odds ratio, 0.1; 95% confidence interval, 0-0.5; P = .009).Conclusion: Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. Confirmation in a multicenter randomized trial is needed. [ABSTRACT FROM AUTHOR]

Objective: To assess health-related quality of life (HRQOL) and behavioral functioning in children and adolescents treated before birth with intrauterine intravascular blood transfusion for alloimmune anemia.Study Design: Cross-sectional cohort study conducted at the Dutch referral center for the management of fetal alloimmune anemia. Follow-up data were available for 285 children at a mean age of 10.5 years (range, 3-21.5 years) with a response rate for questionnaires of 97%. Child-, adolescent-, and parent-rated HRQOL was evaluated with The Netherlands Organization for Applied Scientific Research Child/Adult Quality of Life Questionnaire (TACQOL/TAAQOL). Parents reported on behavioral functioning with the Strengths and Difficulties Questionnaire. Scores were compared with Dutch norm data.Results: Significantly lower scores were reported by parents of children 6-11 years of age compared with Dutch norms on 3 scales: cognitive functioning, social functioning, and positive emotions (P < .00, P = .02, and P = .04). In children aged 8-11 years only the cognitive functioning scale score was significantly lower compared with Dutch norms (P = .01). The children aged 12-15 years reported higher scores on the negative emotions scale (P = .02). When corrected for multiple testing, only the parent-rated cognitive functioning scale remained significant (P < .001). Regarding the HRQOL scores of adolescents aged ≥16 years, no differences were detected. Overall, behavioral difficulties were reported in 37/246 (15%) children aged 3-16 years, and were associated with maternal educational levels (P < .001).Conclusion: Parents reported lower scores on cognitive functioning in their children aged 6-11 years compared with norms. Behavioral difficulties were more prevalent than norms, and were associated with maternal educational level. Outcomes of children after intrauterine intravascular blood transfusion were quite good overall. [ABSTRACT FROM AUTHOR]

Anhydramnios is a rather common ultrasound finding, usually caused by ruptured membranes, placental dysfunction, or impaired fetal renal function. We present a case of anhydramnios, resulting from the perforation of a fetal leg through the uterine wall. Neonatal death occurred caused by severe lung hypoplasia. The absence of clinical symptoms strongly suggests a preexisting weak spot in the uterine wall, presumably resulting from an unrecognized perforation at a previous curettage procedure. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Many women with a bipolar disorder are of reproductive age and will need to continue lithium treatment during pregnancy. The teratogenic and perinatal effects of lithium are known, but not the long-term effects of lithium on neurodevelopment of the children. This study investigates growth, neurological, cognitive and behavioral development of children exposed to lithium in utero. Method: In an observational retrospective cohort study 15 children who were exposed to lithium in utero were investigated at 3–15years of age. Neurological development was tested using the Hempel or Touwen examination. Cognitive development was assessed with the Bayley Scales of Infant Development III, Wechsler Preschool and Primary Scale of Intelligence or the Wechsler Intelligence Scale for Children. Parents completed the Child Behavior Checklist to assess behavioral development and a standard questionnaire about general development of the child since birth. Results: One child had signs of a minor neurological dysfunction, but without further clinical implications. The results of the cognitive tests were within normal limits, although most children had lower scores on the performance IQ subtest. Growth, behavior and general development were within the normal range. Conclusions: Continuing lithium therapy during pregnancy did not cause adverse effects on growth, neurological, cognitive and behavioral development of exposed children. [Copyright &y& Elsevier]