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Background: Unfavorable lipid profile is associated with pregnancy disorders characterized by uteroplacental dysfunction, including hypertensive disorders of pregnancy, preterm birth and fetal growth restriction. None of current tools used to predict the risk of pregnancy complications include lipid levels., Objective(s): In this study, we examined the association of preconception lipid profile with pregnancy disorders characterized by uteroplacental dysfunction in a multi-ethnic population, aiming to improve the identification of women at high risk for uteroplacental dysfunction using current prediction models., Study Design: We conducted a linkage study combining lipid profile collected in the multi-ethnic HELIUS study (Amsterdam, 2011-2015), linked with national perinatal registry data on pregnancy complications after inclusion until 2019. We included 1177 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan origin. Associations were studied using Poisson regression. The discriminative ability was assessed for different pregnancy complications of significantly associated lipid parameters when added to commonly used prediction tools for preeclampsia., Results: Preconception triglyceride level was associated with prevalence of hypertensive disorders of pregnancy (e^triglyceride level (mmol/L) adjusted prevalence ratio 1.07, 95% CI 1.00 to 1.14). Age-adjusted prevalence of hypertensive disorders of pregnancy was also higher among women with high LDL-C level, high TC/HDL-C or ≥4 adverse lipid parameters, but most of these findings were not statistically significant when adjusted for demographic, lifestyle and medical characteristics. Addition of triglyceride level and other lipid parameters to the NICE guideline criteria and to the EXPECT prediction tool did not improve discriminative ability for hypertensive disorders of pregnancy, preterm birth or fetal growth restriction., Conclusion(s): Lipid profile did not aid in the identification of women at high risk for pregnancy disorders characterized by uteroplacental dysfunction. Further studies are needed to improve preconception prediction models for hypertensive disorders of pregnancy and other pregnancy disorders characterized by uteroplacental dysfunction using biomarkers or other easily available measurements., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Abnormal levels of first trimester placental biomarkers are associated with the development of placental syndrome (PS). However, prediction performance is moderate, possibly explained by the clinical heterogeneity of PS. Aim of this study is to investigate the association between first trimester biomarkers and the presence of maternal vascular malperfusion (MVM), as a marker for placental insufficiency., Methods: This retrospective study included 195 women with available first trimester blood sample and placenta histological sections for examination at the Maastricht University Medical Centre. Women were divided into 4 groups, based on the presence of having MVM lesions and/or PS. Levels of PAPP-A, PlGF and sFlt-1 were measured and MVM lesions were classified according to the Amsterdam Placental Workshop Group Consensus Statement., Results: MVM occurrence was observed in 32% of the uncomplicated pregnancies. Women with MVM (regardless of the PS) had lower levels of PAPP-A (p = 0.038) and sFLt-1 (p = 0.006), and a non-significant trend for lower PlGF and sFlt-1/PlGF ratio compared to women without MVM. Low PAPP-A levels individually and in combination with the presence of PS was significantly associated with MVM lesions (aOR = 3.0 and 6.1, respectively), as did the combination of low PlGF levels and PS (aOR = 4.6). In women with PS, having MVM increased the incidence of fetal growth restriction, small for gestational age neonates, lower birthweight and adverse neonatal outcome., Discussion: Our findings suggest that MVM lesions were found to be associated with increased obstetric risks due to early placental dysfunction that can potentially be predicted by the use of first trimester biomarkers., Competing Interests: Declaration of competing interest There are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome., Methods: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated., Results: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress., Conclusion: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation., (© 2020 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Antenatal detection of intrauterine growth restriction remains a major obstetrical challenge, with the majority of cases not detected before birth. In these infants with undetected intrauterine growth restriction, the diagnosis must be made after birth. Clinicians use birthweight charts to identify infants as small-for-gestational-age if their birthweights are below a predefined threshold for gestational age. The choice of birthweight chart strongly affects the classification of small-for-gestational-age infants and has an impact on both research findings and clinical practice. Despite extensive literature on pathological risk factors associated with small-for-gestational-age, controversy exists regarding the exclusion of affected infants from a reference population., Objective: This study aims to identify pathological risk factors for abnormal fetal growth, to quantify their effects, and to use these findings to calculate prescriptive birthweight charts for the Dutch population., Materials and Methods: We performed a retrospective cross-sectional study, using routinely collected data of 2,712,301 infants born in The Netherlands between 2000 and 2014. Risk factors for abnormal fetal growth were identified and categorized in 7 groups: multiple gestation, hypertensive disorders, diabetes, other pre-existing maternal medical conditions, maternal substance (ab)use, medical conditions related to the pregnancy, and congenital malformations. The effects of these risk factors on mean birthweight were assessed using linear regression. Prescriptive birthweight charts were derived from live-born singleton infants, born to ostensibly healthy mothers after uncomplicated pregnancies and spontaneous onset of labor. The Box-Cox-t distribution was used to model birthweight and to calculate sex-specific percentiles. The new charts were compared to various existing birthweight and fetal-weight charts., Results: We excluded 111,621 infants because of missing data on birthweight, gestational age or sex, stillbirth, or a gestational age not between 23 and 42 weeks. Of the 2,599,640 potentially eligible infants, 969,552 (37.3%) had 1 or more risk factors for abnormal fetal growth and were subsequently excluded. Large absolute differences were observed between the mean birthweights of infants with and without these risk factors, with different patterns for term and preterm infants. The final low-risk population consisted of 1,629,776 live-born singleton infants (50.9% male), from which sex-specific percentiles were calculated. Median and 10th percentiles closely approximated fetal-weight charts but consistently exceeded existing birthweight charts., Conclusion: Excluding risk factors that cause lower birthweights results in prescriptive birthweight charts that are more akin to fetal-weight charts, enabling proper discrimination between normal and abnormal birthweight. This proof of concept can be applied to other populations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to explore developmental outcomes at five years after early-onset fetal growth restriction (FGR)., Study Design: Retrospective data analysis of prospective follow-up of patients of three Dutch centres, who participated in a twenty centre European randomized controlled trial on timing of delivery in early-onset FGR. Developmental outcome of very preterm infants born after extreme FGR is assessed at (corrected) age of five., Results: Seventy-four very preterm FGR children underwent follow-up at the age of five. Mean gestational age at birth was 30 weeks and birth weight was 910 g, 7% had a Bayley score <85 at two years. Median five years' FSIQ was 97, 16% had a FSIQ < 85, and 35% had one or more IQ scores <85. Motor score ≤ 7 on movement ABC-II (M-ABC-II-NL) was seen in 38%. Absent or reversed end-diastolic flow, gestational age at delivery, birthweight and neonatal morbidity were related to an FSIQ < 85. Any abnormal IQ scale score was related to birthweight, male sex and severity of FGR, and abnormal motor score to male sex and bronchopulmonary dysplasia (BPD)., Conclusions: Overall, median cognitive outcome at five years was within normal range, but 35% of the children had any abnormal IQ score at age five, depending on the IQ measure, and motor impairment was seen in 38% of the children. GA at delivery, birthweight, EDF prior to delivery and neonatal morbidity were the most important risk factors for cognitive outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: During the H1N1/09 pandemic, pregnant women in the Netherlands were vaccinated with an adjuvanted vaccine. During pregnancy, the maternal immune system changes to enable placental development and growth and acceptance of the semi-allogeneic fetus. As an adjuvant is a pro-inflammatory substance, it may interfere with these immunological changes, resulting in poor placentation or placental growth, which may result in preeclampsia (PE) and fetal intra-uterine growth restriction (IUGR). This study investigated a possible association between adjuvanted H1N1/09 vaccination and the development of PE and/or IUGR., Study Design: Case-control study. Cases were Dutch women with PE and/or IUGR occurring during H1N1/09 vaccination program. Controls had uncomplicated pregnancies during the same period. Maternal characteristics, pregnancy and neonatal outcomes were collected from medical files. Participants were contacted by telephone to enquire about vaccination. Data were analyzed using t-tests, Chi-square tests or Fisher's exact tests. Multivariate analysis was conducted to control for confounders., Results: We included 254 cases and 247 controls. Of the cases, 90 (35.4%) were vaccinated, compared to 87 (35.2%) of the controls (OR:1.009, 95% CI:0.70-1.46, p:0.961). The majority (73.5%) had been vaccinated in second and third trimester. In multivariate analysis, there were no confounders influencing these results. Exploratory subgroup analysis did not show an association between vaccination status in subgroups of women with either PE or IUGR., Conclusion: Our study showed no association between adjuvanted H1N1/09 vaccination and PE and/or IUGR., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To study the association between velamentous cord insertion (VCI) and different outcomes in monochorionic twins with and without twin-twin transfusion syndrome (TTTS)., Methods: We recorded the cord insertion type in all consecutive monochorionic placentas examined in two tertiary medical centers. The association between VCI and several outcomes was estimated., Results: A total of 630 monochorionic placentas with TTTS (n = 304) and without TTTS (n = 326) were studied. The incidence of VCI in the TTTS and non-TTTS group was 36.8% and 35.9%, respectively (P = 0.886). The presence of VCI in one twin was significantly associated with small for gestational age (SGA) status (odds ratio [OR] 1.45, 95% CI 1.13, 1.87) and severe birth weight discordance (OR 3.09, 95% CI 1.93, 4.96). Our results also showed significant interaction between TTTS and VCI when we considered intrauterine fetal demise (IUFD) and gestational age (GA) at birth. The prevalence of IUFD in monochorionic pregnancies without TTTS increased from 4.6% to 14.1% in the presence of VCI (P = 0.027). In the TTTS group, the prevalence of IUFD was comparable in the absence or presence of VCI. Similarly, GA at birth was significantly lower in the presence of VCI only in the non-TTTS group., Conclusion: Our findings suggest that VCI is not associated with the development of TTTS but increases the risk of adverse outcomes. Both VCI and TTTS independently increase the prevalence of IUFD and lower GA at birth in a similar way, showing that VCI is an important indicator of adverse perinatal outcome in monochorionic twins., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: South Asian babies born in developed countries are generally lighter than babies from other ethnic groups born in the same country. While the mean birth weight of Caucasian babies in the Netherlands has increased the past decades, it is unknown if the mean birth weight of South Asian babies born in the Netherlands has increased or if the prevalence of low birth weight (LBW) or small-for-gestational-age (SGA) has decreased.The aims of this study are: 1. to investigate secular changes in mean birth weight and the prevalence of LBW and SGA in Surinamese South Asian babies, and 2. to assess differences between Surinamese South Asian and Dutch Caucasian neonates born 2006-2009., Methods: A population based study for which neonatal characteristics of 2014 Surinamese South Asian babies, born between 1974 and 2009 in the Netherlands, and 3104 Dutch Caucasian babies born 2006-2009 were obtained from well-baby clinic records. LBW was defined as a birth weight <2500 g. SGA was based on a universal population standard (the Netherlands) and three ethnic specific standards (the Netherlands, UK, Canada)., Results: In Surinamese South Asian babies from 1974 to 2009 no secular trend in mean birth weight and prevalence of LBW was found, whereas SGA prevalence decreased significantly.Surinamese South Asian babies born in 2006-2009 (2993 g; 95% CI 2959-3029 g) were 450 g lighter than Dutch Caucasian babies (3448 g; 95% CI 3429-3468 g), while LBW and SGA prevalences, based on universal standards, were three times higher. Application of ethnic specific standards from the Netherlands and the UK yielded SGA rates in Surinamese South Asian babies that were similar to Dutch. There were considerable differences between the standards used., Conclusion: Since 1974, although the mean birth weight of Surinamese South Asian babies remained unchanged, they gained a healthier weight for their gestational age.

Objective: Small-for-gestational-age (SGA) neonates are at increased risk of adverse pregnancy outcome. Our objective was to study the recurrence rate of SGA in subsequent pregnancies., Study Design: A prospective national cohort study of all women with a structurally normal first and subsequent singleton pregnancy from 1999-2007. SGA was defined as birthweight <5th percentile for gestation. We compared the incidence and recurrence rate of SGA for women in total and with and without a hypertensive disorder (HTD) in their first pregnancy. Moreover, we assessed the association between gestational age at first delivery and SGA recurrence., Results: We studied 259,481 pregnant women, of whom 12,943 women (5.0%) had an SGA neonate in their first pregnancy. The risk of SGA in the second pregnancy was higher in women with a previous SGA neonate than for women without a previous SGA neonate (23% vs 3.4%; adjusted odds ratio, 8.1; 95% confidence interval, 7.8-8.5) and present in both women with and without an HTD in pregnancy. In women without an HTD, the increased recurrence risk was independent of the gestational age at delivery in the index pregnancy; whereas in women with an HTD, this recurrence risk was increased only when the woman with the index delivery delivered at >32 weeks' gestation., Conclusion: Women with SGA in their first pregnancy have a strongly increased risk of SGA in the subsequent pregnancy and first pregnancy SGA delivers a significant contribution to the total number of second pregnancy SGA cases., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions., Methods: In 372 women with a history of vascular complicated pregnancy, we assessed thyroid function., Results: Subclinical hypothyroidism was diagnosed in 73/372 women (19.6%). It occurred more often when pregnancy ended before 32 weeks of gestation (p = 0.008)., Conclusion: In this cohort, subclinical hypothyroidism is more common after very preterm delivery. It may contribute to the elevated risk of remote cardiovascular disease.

Objective: To examine the association between maternal age and birth outcomes, and to investigate the role of sociodemographic and lifestyle-related determinants., Design: Population-based prospective cohort study from early pregnancy onwards., Setting: Rotterdam, the Netherlands., Population: A cohort of 8568 mothers and their children., Methods: Maternal age was assessed at enrolment. Information about sociodemographic (height, weight, educational level, ethnicity, parity) and lifestyle-related determinants (alcohol consumption, smoking habits, folic acid supplement use, caffeine intake, daily energy intake) and birth outcomes was obtained from questionnaires and hospital records. Multivariate linear and logistic regression analyses were used., Main Outcomes Measures: Birthweight, preterm delivery, small-for-gestational-age, and large-for-gestational-age., Results: As compared with mothers aged 30-34.9 years, no differences in risk of preterm delivery were found. Mothers younger than 20 years had the highest risk of delivering small-for-gestational-age babies(OR 1.6, 95% CI: 1.1-2.5); however, this increased risk disappeared after adjustment for sociodemographic and lifestyle-related determinants. Mothers older than 40 years had the highest risk of delivering large-for-gestational-age babies (OR 1.3, 95% CI: 0.8-2.4). The associations of maternal age with the risks of delivering large-for-gestational-age babies could not be explained by sociodemographic and lifestyle-related determinants., Conclusions: As compared with mothers aged 30-34.9 years, younger mothers have an increased risk of small-for-gestational-age babies, whereas older mothers have an increased risk of large-for-gestational-age babies. Sociodemographic and lifestyle-related determinants cannot fully explain these differences., (© 2011 The Authors Journal compilation © RCOG 2011 BJOG An International Journal of Obstetrics and Gynaecology.)

Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective.

Objective: Small for gestational age (SGA) is associated with increased neonatal morbidity and mortality. At present, evidence on whether these pregnancies should be managed expectantly or by induction is lacking. To get insight in current policy we analysed data of the National Dutch Perinatal Registry (PRN)., Methods: We used data of all nulliparae between 2000 and 2005 with a singleton in cephalic presentation beyond 36+0 weeks, with a birth weight below the 10th percentile. We analysed two groups of pregnancies: (I) with isolated SGA and (II) with both SGA and hypertensive disorders. Onset of labour was related to route of delivery and neonatal outcome., Results: Induction was associated with a higher risk of emergency caesarean section (CS), without improvement in neonatal outcome. For women with isolated SGA the relative risk of emergency CS after induction was 2.3 (95% Confidence Interval [CI] 2.1 to 2.5) and for women with both SGA and hypertensive disorders the relative risk was 2.7 (95% CI 2.3 to 3.1)., Conclusion: Induction in pregnancies complicated by SGA at term is associated with a higher risk of instrumental deliveries without improvement of neonatal outcome. Prospective studies are needed to determine the best strategy in suspected IUGR at term.

Introduction: Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma., Methods: This study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations., Results: We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls., Conclusions: This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.

Objective: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era., Methods: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin., Results: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence after early (symmetric) intrauterine growth retardation was more pronounced than after later (asymmetric) intrauterine or neonatal growth retardation. These differences in mean IQ remained when participants with overt handicaps were excluded., Conclusions: Prematurity as well as the timing of growth retardation are important for later intelligence. Parental education, however, best predicted later intelligence in very preterm or very low birthweight infants.

Background: Various studies have shown an association between low birth weight and the prevalence of elevated blood pressure later in life. However, a relationship between birth weight and blood pressure in the neonatal period has not been investigated yet., Objective: To study the relationship between birth weight and blood pressure during the first week of life., Methods: Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were measured every 8 h during days 1, 2, 3, 4 and 7 in 44 small for gestational age (SGA) infants and compared with those of infants born with a birth weight appropriate for gestational age (AGA). The infants were matched for gestational age and gender., Results: Meanbirth weight (range) in the SGA group was 778 (460-1,400) g versus 1,524 (960-2,730) g in the AGA group, and mean (range) gestational age of both groups was 30.5 (27.3-35.5) weeks. In the first week of life, SGA and AGA infants had similar SBP, DBP and MBP. Also, after adjustment for confounders (maternal medication, smoking), SBP, DBP and MBP rose equally in SGA and AGA infants during the first week of life. AGA infants showed a positive correlation between birth weight and blood pressure, but SGA infants showed an inverse correlation., Conclusions: Although differences in blood pressure were found between SGA and AGA infants in the first week of life, the inverse relationship between birth weight and blood pressure in SGA infants warrants follow-up studies to investigate a possible link with late cardiovascular disease., (Copyright 2009 S. Karger AG, Basel.)

Objective: To analyse the association between neighbourhood, ethnicity and adverse perinatal outcome in pregnant women from the 4 largest cities (Amsterdam, Rotterdam, The Hague and Utrecht; G4) and elsewhere in The Netherlands., Design: Descriptive, retrospective., Method: The perinatal outcome of 877,816 single pregnancies during the years 2002-2006, derived from The Netherlands Perinatal Registry, was analysed for the ethnicity (Western or non-Western) and the neighbourhood (deprived or not) of the pregnant women in the G4 and elsewhere in The Netherlands. Adverse perinatal outcome was defined as perinatal mortality, congenital abnormalities, intra-uterine growth restriction, preterm birth, Apgar score after 5 minutes < 7 and/or admission to a neonatal intensive-care unit., Results: The overall perinatal mortality rate was higher in the G4 than elsewhere in The Netherlands (11.1 per thousand versus 9.3 per thousand; p < 0.001; 95% confidence interval of the difference: 1.2-2.4 per thousand). The same was true for the sum of adverse perinatal outcomes (154.9 per thousand versus 138.9 per thousand). In the G4 the perinatal mortality among non-Western women was higher than among Western women (13.2 per thousand versus 9.5 per thousand). Residing in Dutch deprived neighbourhoods was associated with a higher perinatal mortality than outside deprived neighbourhoods (13.5 per thousand versus 9.3 per thousand). The relative risks of living in deprived neighbourhoods for adverse pregnancy outcomes are higher among Western than among non-Western women., Conclusion: Pregnant women in the G4 have an increased risk ofadverse perinatal outcomes. The risks of residing in a deprived neighbourhood are even higher, especially among Western women. The findings are important for new strategies to improve perinatal outcomes.

Preeclampsia and intrauterine growth restriction are related, pregnancy-specific disorders with a substantial genetic influence, which may have a joint genetic aetiology. We investigated familial aggregation, consanguinity and parent-of-origin effects for preeclampsia and IUGR. Fifty women with previous preeclampsia and 56 with previous pregnancies complicated by intrauterine growth restriction were recruited from a recent genetically isolated population in the Netherlands. Their relationships were estimated by means of a large genealogy database that contains information on more than 110 000 individuals from the isolate over 23 generations. Relationships were quantified using kinship and inbreeding coefficients. Parent-of-origin effects were evaluated by comparing parental kinships. Eighty-six women (39 preeclampsia and 47 intrauterine growth restriction) could be linked to one common ancestor within 14 generations. The proportion of related women with previous preeclampsia (95.6%) or pregnancies complicated by intrauterine growth restriction (95.1%) was significantly greater than expected by chance (P<0.001). Combined analysis of both disorders did not change the magnitude of familial aggregation. The proportion of women born from consanguineous marriages was increased in women with previous preeclampsia (81.8%) and those with intrauterine growth restriction (78%) compared to a random sample (P<0.001). Maternal and paternal kinships were not significantly different in both disorders. We demonstrate cosegregation of preeclampsia and intrauterine growth restriction, supporting a common genetic aetiology. The high proportion of parental consanguineous marriages suggests the possibility of an underlying recessive mutation. No evidence was found for a parent-of-origin effect either in preeclampsia or in intrauterine growth restriction.

Background: Assessment of general movements (GMs) at three months is considered useful for prediction of adverse neurological outcome in high risk infants., Aims: To study the prevalence of abnormal GMs in infants born from women with early-onset hypertensive disorders of pregnancy and the association of GMs with neurodevelopmental outcome at one year., Study Design: Prospective study, part of a randomised controlled trial of pre-birth management strategies., Subjects: Infants born from women with early-onset hypertensive disorders of pregnancy., Outcome Measures: GMs observation and neurological examination at term and three months corrected age; at one year neurological examination and Bayley Scales of Infant Development., Results: From 216 women included, 175 of 178 surviving infants (mean gestational age 31.6 weeks [SD 2.3], mean birth weight 1346 grams [SD 458]), were examined at three months. At term age normal, mildly abnormal and definitely abnormal GMs were observed in 54%, 36% and 10% respectively; and at three months in 47%, 40% and 13%. Mildly or definitely abnormal GMs at three months were not associated with abnormal neurological examination at one year, however, they were associated with delayed psychomotor development at one year (p = 0.01)., Conclusions: In this prospective study, including small for gestational age, preterm infants about half of them did not have normal GMs at term and three months. There was no association of GMs at term nor three months with neurological outcome at one year, but there was a significant association of GMs at three months with one year psychomotor development.

Objective: To assess associations between vitamin-dependent homocysteine metabolism and vascular-related pregnancy complications by considering interval between delivery and postpartum investigation and maternal age., Methods: Case-control study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104). Controls comprised 176 women with uncomplicated obstetric histories. Oral methionine loading tests and fasting vitamin profiles were performed more than 6 weeks after delivery. Odds ratios and 95% confidence intervals were calculated after logistic regression analysis., Results: Hyperhomocysteinemia was associated with an approximately 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abruptio placentae, and intrauterine growth restriction. Cobalamin deficiency was associated with HELLP syndrome, abruptio placentae, intrauterine growth restriction, and intrauterine fetal death. Pyridoxal 5-phosphate deficiency increased the risk for pregnancy-induced hypertension 4-fold. These associations lost their significance after adjustment for time interval and maternal age. High red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was associated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, and abruptio placentae., Conclusion: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investigation and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.

Objective: To evaluate the effect of antenatal corticosteroids on mortality, morbidity, and disability or handicap rate in early preterm, growth-restricted infants., Methods: This case-control study in two tertiary care centers included all live-born singleton infants with growth-restriction due to placental insufficiency, who were delivered by cesarean because of cardiotocographic signs of fetal distress before the beginning of labor at a gestational age of 26-32 weeks during the years 1984-1991. Infants who had been treated antenatally with corticosteroids more than 24 hours and less than 7 days before birth were matched by birth weight, sex, and year of birth with infants whose mothers had been admitted more than 24 hours before delivery but were not treated antenatally with steroids. The main outcome measure was survival without disability or handicap at 2 years corrected age. A sample of 60 case-control pairs would give 81% power to demonstrate 50% increase of this outcome [odds ratio (OR) 3.0] by corticosteroid treatment. Behavior and physical growth were evaluated at school age by questionnaire., Results: The study group and control group consisted of 62 infants each. Survival without disability or handicap at 2 years' corrected age was more frequent in the corticosteroid group [OR 3.2, confidence interval (CI) 1.1, 11.2]. In the long-term follow-up at school age there was a statistically significant negative effect on physical growth (OR 5.1, CI 1.4, 23.8), but no differences in behavior were detected., Conclusion: Benefits from antenatal corticosteroids for early preterm, growth-restricted infants appear to outweigh possible adverse effects.

Background: Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944-45., Methods: We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants)., Findings: Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p = 0.006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5.8 mmol/L; concentrations were 0.5 mmol/L (95% CI 0.1-0.9) higher among participants exposed during late gestation, 0.4 mmol/L (0-0.8) higher among those exposed during mid gestation, and 0.1 mmol/L (-0.4 to 0.6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p = 0.05) and 2 h insulin concentrations (p = 0.04), which suggests an association with insulin resistance., Interpretation: Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.

The authors examined the effects of maternal intrauterine undernutrition on offspring birth weights in a cohort of women born between August 1944 and April 1946 in Amsterdam, The Netherlands. This period included the Dutch Hunger Winter, a war-induced famine. Undernutrition was defined separately for each trimester of pregnancy as an average supply of less than 1,000 calories per day from government food rations. For maximum control of potential maternal confounding factors related to offspring birth weight, the authors performed a within-family analysis, including 437 families with two siblings and 107 families with three siblings born between 1960 and 1985. As in other studies of the famine, maternal birth weight itself was decreased after third trimester intrauterine exposure but not after first trimester exposure. The expected increase in offspring birth weights with increasing birth order was not seen after maternal intrauterine exposure in the first trimester of pregnancy. In this group, second born infants weighed, on average, 252 g less at birth than their firstborn siblings (95% confidence interval (CI) -419 to -85), and thirdborn infants weighed 419 g less (95% CI -926 to 87), even after adjustment for trimester of maternal intrauterine exposure, maternal birth weight, smoking during pregnancy, and sex of infants in the sibling pairs. Additional adjustment for the birth weight of the elder sibling did not materially change this abnormal pattern. There were no abnormal patterns in offspring birth weights after maternal intrauterine exposure in the second or third trimester of pregnancy. The study outcomes could not be explained by other selected determinants of birth weight, by lack of control for socioeconomic status, or by loss to follow-up of the 1944-1946 birth cohort. This study suggests that there may be long-term biologic effects, even into the next generation, of maternal intrauterine undernutrition which do not correspond to the effects on the mothers' own birth weights.

Risk factors during pregnancy and delivery and neurological morbidity of newborns were assessed in a birth cohort in Dominica, the Caribbean. The data were compared with two reference groups, one from Grenada, the Caribbean, and the other from Groningen, the Netherlands. Despite variations in cultural and socio-economic situation, the similarities in obstetrical conditions, neonatal neurological morbidity and perinatal relationships between the three groups were more striking than the differences. The Dominican group showed a significantly higher rate of preterm births than the two other groups. Preterm birth was associated with a significant increase in neurological deviancy. In general motility and muscle tone were found to be lower in the Caribbean region than in the Netherlands.