Gerald Hackett

• Consultant at Cambridge University Hospitals NHS Foundation Trust

Background Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. Here we investigate whether fe...

Background Research indicates that structural differences exist in the brains of individuals who later display developmental conditions (e.g., autism). To date only a handful of studies have explored the relationship between fetal brain growth and later infant outcomes, with a particular focus on fetal head circumference (HC) as a proxy for brain d...

Background Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development. Methods Maternal serum was collected from pregnant women ( n = 122) before or during th...

Background: Elevated prenatal sex steroids and maternal conditions that are related to sex steroids (e.g., polycystic ovary syndrome) have been positively associated with autism likelihood. It is unclear if this is detectable in the maternal circulation, if it relates to maternal autistic traits, and whether it is also predictive of autistic traits...

Objective: This study measured anogenital distance (AGD) during late second/early third trimester of pregnancy to confirm previous findings that AGD can be measured noninvasively in the fetus using ultrasound and further showed differences in reference ranges between populations. Method: Two hundred ten singleton pregnancies were recruited at th...

Table S1. Study characteristics and prevalence of endometrial cancer in premenopausal women.

Appendix S1. Search strategies.

Figure S1. Subgroup analysis.

What's Already Known About This Topic? Costello syndrome is a rare multisystem disorder, which is usually diagnosed by postnatal findings including macrosomia, significant failure to thrive, developmental and intellectual disability, coarse facial features, cardiac and skin abnormalities and short stature as well as a susceptibility to childhood an...

\textbf{Background}$ Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. $\textbf{Objectives}$ To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnorma...

Background Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. Objectives To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding....

Background Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-ol...

Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fet...

Background: It has been suggested that autism may be an extreme manifestation of specific (but not all) male-typical traits, both in terms of cognition and neuroanatomy. Studies of prenatal exposure to sex steroid hormones during critical periods of development are related to specific (but not all) sexually dimorphic aspects of cognition and behavi...

Objective To define the morphological and histological characteristics in the placentas of infants admitted to the Neonatal Unit admitted at and/or near term compared to those not. Methods In a prospective study, 1,153 unselected women with singleton pregnancies, delivering at 34-43 weeks of gestation were recruited in a single UK maternity unit. O...

Falling consent rates for postmortems, regardless of age of death, have been widely reported in recent years. The aim of this study was to explore parental attitudes to, and decision-making about, a perinatal postmortem after termination for fetal abnormality, late miscarriage, or stillbirth. A prospective self-completion questionnaire was given to...

In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) p...

Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of...

This study investigated whether fetal testosterone (FT) measured from second trimester amniotic fluid was related to specific aspects of visuospatial ability, in children aged 7-10 years (35 boys, 29 girls). A series of tasks were used: the children's Embedded Figures Test (EFT) (a test of attention to detail), a ball targeting task (measuring hand...

ABSTRACT Objective To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality. Design Prospective self-completion questionnaire. Setting UK fetal medicine and delivery unit. Patients 35 women and their partners after second o...

Whilst individual histological features are well described, there are no universally agreed criteria as to what constitutes a clinically significant histological lesion of the placenta in an uncomplicated pregnancy, nor has the presence of such histological findings been systematically related to quantitative morphological characteristics of the pl...

Background: The position of the placental cord insertion, its shape and cord coiling are thought to be associated with perinatal outcome. This study derives indices describing the relationship of cord insertion to the placental centre, the shape of the placenta and cord coiling in placentas from unselected term pregnancies. Further, we investigate...

Methods: This 4 1 2 year retrospective study is based on 71 fetuses where termination of pregnancy (TOP) was performed because of a fetal malformation and/or chromosomal anomaly. Only fetuses who had undergone both fetal anatomy scanning and autopsy were included. Sensitivity and specificity of ultrasound findings with regard to autopsy findings we...

We sought to define the relationship between first trimester fetal growth, pregnancy-associated plasma protein A (PAPP-A) levels and birthweight. Two-hundred and one women with repeat first trimester crown-rump length (CRL) measurements were included. In 194, the first trimester PAPP-A value was known and in 169 there was complete data including bi...

Objectives Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit t...

Autism spectrum conditions have been characterised as an extreme presentation of certain male-typical psychological traits. In addition, several studies have established a link between prenatal exposure to testosterone and cognitive sex differences in later life, and one study found that foetal testosterone (FT) is positively correlated to autistic...

The performance of pregnancy-associated plasma protein-A (PAPP-A) as a first trimester trisomy 21 marker is hypothesized to improve below 11 weeks, whereas beta-human chorionic gonadotrophin (hCG) is better after 14 weeks. We audited a model combining early PAPP-A (9-10 weeks) with NT (11-13 weeks and 6 days) and early triple test (>14 weeks). A to...

Mammals, including humans, show sex differences in juvenile play behavior. In rodents and nonhuman primates, these behavioral sex differences result, in part, from sex differences in androgens during early development. Girls exposed to high levels of androgen prenatally, because of the genetic disorder congenital adrenal hyperplasia, show increased...

Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the pos...

To determine the feasibility of percutaneous fetal organ biopsies in the context of a 'minimally invasive' perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. Th...

To determine the early outcome and the incidence of associated structural anomalies in pregnancies complicated by severe fetal ventriculomegaly (VM). A review of cases of severe fetal VM (posterior horn of lateral ventricle > 15 mm at referral or during prenatal follow-up) referred to a fetal medicine centre in Eastern England over 4 years from 200...

Postmortem magnetic resonance imaging (MRI) may be an alternative to conventional autopsy. However, it is unclear how confident radiologists are in reporting such studies. We sought to determine the confidence with which radiologists report on various fetal organs by developing a scale to express their confidence of normality and abnormality, and t...

This study examines foetal testosterone (fT) levels (measured in amniotic fluid) as a candidate biological factor, influencing sex differences in systemizing. Systemizing is a cognitive process, defined as the drive to analyze or construct systems. A recent model of psychological sex differences suggests that this is a major dimension in which the...

Objectives Following perinatal death, organ weights at autopsy may provide evidence of growth restriction and pulmonary hypoplasia. Whilst postmortem magnetic resonance imaging (MRI) may provide comparable information to autopsy about structural abnormalities, its ability to provide reproducible data about organ size has yet to be determined. We ex...

Empathy involves an understanding of what others are thinking and feeling, and enables us to interact in the social world. According to the Empathizing-Systemizing (E-S) theory, females on average have a stronger drive to empathize than males. This sex difference may in part reflect developmental differences in brain structure and function, which a...

In animals, fetal testosterone (fT) plays a central role in organizing the brain and in later social behavior. In humans, exposure to atypical levels of prenatal androgens may result in masculine behavior and ability patterns. Normal inter-individual variation in fT levels has also been correlated with later sex-typed behavior. In the current study...

To determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan. A prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 1...

Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of 53...

Aims and methods: To determine obstetrical and neonatal outcomes in referrals of apparently isolated mild ventriculomegaly following routine ultrasound scan, over the period 2001-2003. Specialist ultrasound and other investigations were performed. Neonatal examination and postnatal ultrasound findings were collected and local neurodevelopmental fo...

We report a case of ruptured splenic artery aneurysm during labor in which the clinical signs were masked by epidural analgesia. A high index of clinical suspicion must be maintained in cases of atypical epidural breakthrough pain, and attending clinicians must be prepared for the unexpected when faced with a maternal collapse.

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB...

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB...

To assess the potential of both urinary albumin creatinine ratios and urinary calcium-creatinine ratios as screening tests for pregnancy-induced hypertension. A prospective, non-interventional study was performed in a teaching hospital antenatal clinic. Five hundred normotensive, nulliparous pregnant women provided a urine sample at 19 weeks' gesta...

To determine the levels in serum of tissue inhibitor of metalloproteinases (TIMP) in pregnancy and to examine the possibility of a time course in relation to parturition, both term and preterm. Serum tissue inhibitor of metalloproteinases was measured using an enzyme-linked immunosorbent assay. A cross-sectional study was conducted in 333 women dur...

Serum levels of tissue collagenase, matrix metalloproteinase-1, were measured in both longitudinal and cross-sectional studies, in 332 pregnant women and 27 non-pregnant volunteers. The enzyme-linked immunosorbent assay (ELISA) used is the first described to measure collagenase in serum directly, is specific, and is rapid and reproducible. Levels w...

Fetal nucleated cells in the maternal circulation constitute a potential source of cells for the non-invasive prenatal diagnosis of fetal genetic abnormalities. We have investigated the use of the Magnetic Activated Cell Sorter (MACS) for enriching fetal nucleated erythrocytes. Mouse monoclonal antibodies specific for CD45 and CD32 were used to dep...

Animal studies have suggested a detrimental effect of exercise on uterine blood flow, but it is unclear whether the same responses occur in human pregnancy. Thirty-four women in the third trimester of singleton pregnancies underwent a bicycle exercise test during which a pulsed Doppler method was used to assess the response of the uteroplacental ci...

Early arnniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstaine...

One hundred and fourteen samples of amniotic fluid taken before 15 weeks of gestation were cultured for cytogenetic studies. The results of culturing these early amniotic fluid (EAF) samples were compared with the results of culturing 114 standard amniotic fluid (SAP) samples taken after 15 weeks of gestation matched for maternal age and received i...

Ten-ml samples of amniotic fluid were taken from pregnancies being terminated at 8–14 weeks' gestation. DNA was extracted from the amniotic cells by sequential centrifugation and analysed using the polymerase chain reaction (PCR). Fifteen samples were analysed for evidence of maternal contamination using Mfd5 oligo-nucleotide primers for repeat pol...

The Foley catheter and a 3 mg dinoprostone pessary (Prostin E2) were compared as methods for cervical preparation before second trimester dilatation and evacuation. The catheter was well tolerated and provided significantly greater change in cervical dilatation and improved cervical compliance. The Foley catheter would seem to provide a readily ava...

Variation in indices used to characterize the maximum frequency outline of waveforms obtained from the uteroplacental and fetal circulations by duplex Doppler ultrasound was studied between observers, over a 24-h period and before and after a meal. No significant differences were found. Reference ranges were derived for three indices, the A/B ratio...

Eighty parents were offered an emotional support and counseling service following termination of pregnancy for fetal abnormality detected by second trimester ultrasound examination. Twenty couples took up the invitation to talk about their experiences. It was found that these women and their partners were profoundly affected by their decision to te...

Doppler blood flow studies in 41 pregnancies with oligohydramnios in the second trimester found abnormal patterns in all 14 pregnancies with intrauterine growth retardation but in only one of nine pregnancies with premature rupture of the membranes, and one of 10 with fetal renal defects. Mixed patterns were found in a heterogeneous group of fetuse...

In 82 consecutive cases of intrauterine growth retardation managed by established criteria fetal Doppler studies identified 29 fetuses with absence of end diastolic frequencies in the fetal aorta. These same fetuses were significantly more growth retarded (p less than 0.001) and had an earlier gestational age at delivery (p less than 0.001) than th...

A pulsed Doppler apparatus was used to assess the blood flow velocity profiles in uterine vessels (arcuate arteries) at 16 to 18 weeks' gestation to determine if complications associated with impaired trophoblastic invasion of the placental bed (ie, pregnancy-induced hypertension, intrauterine growth retardation, and fetal asphyxia) could be predic...

In 32 pregnancies complicated by intra-uterine growth retardation, umbilical venous blood was sampled by cordocentesis and the utero-placental blood velocity resistance index (RI) was recorded using Doppler ultrasound. Significant correlations were found between the utero-placental RI and fetal hypoxia, hypercapnea, acidosis, hyperlactaemia and ery...

The significance of intrauterine growth retardation (IUGR) and the methods currently available for assessment of fetal growth are briefly reviewed. The use of Doppler ultrasound assessment of the flow velocity waveform (FVW) of the uteroplacental waveform at 16-18 weeks of gestation is outlined. A pilot study of 127 pregnancies suggested that the s...

In 32 pregnancies complicated by intrauterine growth retardation, umbilical venous blood was sampled by cordocentesis and the utero-placental blood velocity resistance index (RI) was recorded using Doppier ultrasound. Significant correlations were found between the utero-placental RI and fetal hypoxia, hypercapnea, acidosis, hyperlactaemia and eryt...