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Background: Progesterone is widely used in prenatal care. However, long‐term effects of prenatal progesterone treatment on child development are unclear. Objectives: To evaluate long‐term outcomes in children after prenatal progesterone treatment. Search strategy: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. Selection criteria: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. Data collection and analysis: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. Main results: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta‐analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley‐III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference −0.04, 95% Confidence Interval −0.26 to 0.19), I2 = 22%. Heterogeneity prohibited additional meta‐analyses. Other long‐term outcomes showed no differences. Conclusions: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow‐up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of transabdominal amnioinfusion or no intervention on long-term outcomes in children born after second-trimester prelabour rupture of the membranes (PROM between 16+0/7 -24+0/7  weeks) and oligohydramnios.Population: Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL-III (NTR3492).Methods: Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires.Main Outcome Measures: Neurodevelopmental outcomes were measured. Mild delay was defined as -1 standard deviation (SD), severe delay as -2 SD. Healthy long-term survival was defined as survival without neurodevelopmental delay or respiratory problems.Results: In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60-1.22). Follow-up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long-term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53-11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long-term survivor.Conclusions: In this small sample of women suffering second-trimester PROM and oligohydramnios, amnioinfusion did not improve long-term outcomes. Overall, 71% of survivors had no neurodevelopmental delay.Tweetable Abstract: Healthy long-term survival was comparable for children born after second-trimester PROM and treatment with amnioinfusion or no intervention. [ABSTRACT FROM AUTHOR]

Objective: To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years.Design: The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group.Methods: Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health.Main Outcome Measures: The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years.Results: Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects.Conclusion: Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth.Tweetable Abstract: Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour. [ABSTRACT FROM AUTHOR]

Objective: To develop a core outcome set for trials on the treatment of hyperemesis gravidarum (HG).Design: Identification of outcomes is followed by a modified Delphi survey combined with a consensus development meeting and a consultation round.Setting: An international web-based survey combined with a consensus development meeting.Population: Stakeholders including researchers; women with lived experience of HG and their families; obstetric health professionals; and other health professionals.Methods: We used systematic review, semi-structured patient interviews, closed group sessions and Steering Committee input to identify potential core outcomes. We conducted two web-based survey rounds, followed by a face-to-face consensus development meeting and a web-based consultation round.Main Outcome Measures: A core outcome set for research on HG.Results: Fifty-six potential outcomes were identified. The modified Delphi process was completed by 125 stakeholders, the consensus development meeting by 20 stakeholders and the consultation round by 96 stakeholders. Consensus was reached in ten domains on 24 outcomes: nausea; vomiting; inability to tolerate oral fluids or food; dehydration; weight difference; electrolyte imbalance; intravenous fluid treatment; use of medication for hyperemesis gravidarum; hospital treatment; treatment compliance; patient satisfaction; daily functioning; maternal physical or mental or emotional wellbeing; short- and long-term adverse effects of treatment; maternal death; pregnancy complications; considering or actually terminating a wanted pregnancy; preterm birth; small for gestational age; congenital anomalies; neonatal morbidity and offspring death).Conclusions: This core outcome set will help standardise outcome reporting in HG trials.Tweetable Abstract: A core outcome set for treatment of hyperemesis gravidarum in order to create high-quality evidence. [ABSTRACT FROM AUTHOR]

Background: Hyperemesis gravidarum (HG) is a common cause of hospital admission in early pregnancy. There is no international consensus on the definition of HG, or on outcomes that should be reported in trials. Consistency in definition and outcome reporting is important for the interpretation and synthesis of data in meta-analyses.Objective: To identify which HG definitions and outcomes are currently in use in trials.Search Strategy: We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase and (3) Medline for published trials and the WHO-ICTRP database for ongoing trials (27 October 2017).Selection Criteria: All randomised clinical trials reporting on any intervention for HG were eligible.Data Collection and Analysis: Two reviewers independently assessed trial eligibility and extracted data on HG definition and outcomes.Main Results: We included 31 published trials reporting data from 2511 women and three ongoing trials with a planned sample size of 360 participants. We identified 11 definition items. Most commonly used definition items were vomiting (34 trials) and nausea (30 trials). We identified 34 distinct outcomes. Most commonly reported outcomes were vomiting (29 trials), nausea (26 trials), need for hospital treatment (14 trials) and duration of hospital (re)admission(s) (14 trials).Conclusion: There is substantial variation of HG definition and outcome reporting in trials. This hampers meaningful aggregation of trial results in meta-analysis and implementation of evidence in guidelines. To overcome this, international consensus on a definition and a core outcome set for HG trials should be developed.Tweetable Abstract: There is a wide variation of definitions and outcomes reported in trials on hyperemesis gravidarum. [ABSTRACT FROM AUTHOR]

Objective: To investigate the long-term consequences of prenatal exposure to maternal hyperemesis gravidarum upon offspring cardiometabolic risk factors.Design: This study is part of the prospective follow-up of the Northern Finland Birth Cohort 1986.Setting: Between 1 July 1985 and 30 June 1986 all pregnant women in two provinces of Finland were recruited at first antenatal visit (99% of eligible participated).Population: A total of 8953 women with liveborn singleton offspring who consented to having their children followed-up were included.Methods: Hyperemesis gravidarum (HG) was defined as hospitalisation during pregnancy for HG based on the International Classification of Disease (ICD) code. Women who were not hospitalised for HG during pregnancy were used as a reference group. Data on pregnancy and birth outcomes were obtained via medical records and questionnaires; 6462 adolescents, aged 16 years, underwent anthropometric measurements (HG n = 42, reference n = 6420) and 5648 adolescents had a fasting blood sample taken (HG n = 36, reference n = 5612).Main Outcome Measures: Body mass index (BMI), blood pressure, fasting glucose, and lipid levels in offspring.Results: Multivariate regression analyses showed no differences in offspring BMI (kg/m2 ; adjusted percentage difference HG versus reference, 2.2; 95% CI -0.1, 4.6), systolic blood pressure (adjusted difference 2.1 mmHg; 95% CI -1.5, 5.6), and fasting blood glucose (mmol/l; adjusted percentage difference, 2.3; 95% CI -0.6, 5.4), between adolescents born to mothers with and without HG.Conclusions: We found no evidence that prenatal exposure to HG has negative consequences for cardiometabolic health of offspring at the age of 16 years.Tweetable Abstract: Hyperemesis gravidarum does not affect cardiometabolic health in adolescent offspring. [ABSTRACT FROM AUTHOR]

Objective: To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6.Design: Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD).Setting: 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study.Population: Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950).Methods: Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders.Main Outcome Measures: Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6.Results: Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: β 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: β 0.49 beats/min, 95% CI 0.11, 0.87).Conclusion: This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring.Tweetable Abstract: Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring. [ABSTRACT FROM AUTHOR]

Objective: To investigate the consequences of weight loss in pregnancy on pregnancy outcomes and cardiometabolic profile in childhood.Design: Prospective birth cohort (ABCD study).Setting: Between 2003 and 2004, all pregnant women in Amsterdam were approached for study participation.Population: 7818 pregnant women were included, of which 3165 consented to having their children examined at 5-6 years of age. In 1956 children fasting capillary blood samples were also taken.Methods: At antenatal booking, women answered questions about their pregnancy and whether they suffered from severe weight loss (SWL; >5 kg). Pregnancy details and outcomes were available through the obstetric caregiver.Main Outcome Measures: At birth main outcome measures were prematurity (<37 weeks) and birthweight. At follow-up, body mass index (BMI), blood pressure, glucose and lipids were assessed.Results: SWL occurred in 6.8% of cases. Women with SWL had similar preterm birth rates compared with women without these complaints (adjusted OR 1.1, 95%CI 0.7, 1.7). Birthweight (adjusted difference - 31 g, 95%CI -76, 15) and BMI at 5-6 years of age (adjusted difference 0.2 kg/m(2) , 95%CI 0.0, 0.5) were similar in children born to mothers with SWL and without SWL, but blood pressure was increased. For diastolic blood pressure this association was independent of confounders (adjusted difference 1.4 mmHg, 95%CI 0.4, 2.4). Lipid and glucose levels were not significantly different between these groups.Conclusion: Early pregnancy weight loss, usually occurring as a manifestation of hyperemesis gravidarum, could have long-term consequences for offspring health. [ABSTRACT FROM AUTHOR]

Objective We previously showed that maternal under-nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren. Design Historical cohort study. Setting Web-based questionnaire. Population The adult offspring (F2) of a cohort of men and women (F1) born around the time of the 1944-45 Dutch famine. Methods We approached the F2 adults through their parents. Participating F2 adults ( n = 360, mean age 37 years) completed an online questionnaire. Main outcome measures Weight, body mass index ( BMI), and health in F2 adults, according to F1 prenatal famine exposure. Results Adult offspring (F2) of prenatally exposed F1 fathers had higher weights and BMIs than offspring of prenatally unexposed F1 fathers (+4.9 kg, P = 0.03; +1.6 kg/m², P = 0.006). No such effect was found for the F2 offspring of prenatally exposed F1 mothers. We observed no differences in adult health between the F2 generation groups. Conclusions Offspring of prenatally undernourished fathers, but not mothers, were heavier and more obese than offspring of fathers and mothers who had not been undernourished prenatally. We found no evidence of transgenerational effects of grandmaternal under-nutrition during gestation on the health of this relatively young group, but the increased adiposity in the offspring of prenatally undernourished fathers may lead to increased chronic disease rates in the future. [ABSTRACT FROM AUTHOR]

Background: There is evidence that hyperemesis gravidarum (HG) is associated with a predominance of female fetuses, lower birthweights and shorter gestational ages at birth. As the adverse effects of prematurity and low birthweight on disease risk in later life have become increasingly clear, the repercussions of HG might not be limited to adverse perinatal outcomes., Objectives: To summarise the evidence on short- and long-term outcomes of pregnancies with HG., Search Strategy: A literature search was conducted in the electronic databases Medline and Embase., Selection Criteria: Studies were included that reported on the fetal, neonatal and long-term outcome of pregnancies complicated by HG., Data Collection and Analysis: Two authors independently selected studies and extracted data. Meta-analysis was performed using review manager., Main Results: Women with HG during pregnancy were more likely to have a female child (OR 1.27; 95% CI 1.21-1.34). They were also more likely to have a baby with low birthweight (LBW, <2500 kg; OR 1.42; 95% CI 1.27-1.58) that was small for gestational age (SGA; OR 1.28; 95% CI 1.02-1.60), and to deliver prematurely (OR 1.32; 95% CI 1.04-1.68). There was no association with Apgar scores, congenital anomalies or perinatal death. One study described an association between HG and testicular cancer in the offspring., Author's Conclusions: There is evidence that HG is associated with a higher female/male ratio of offspring and a higher incidence of LBW, SGA and premature babies. Little is known about the long-term health effects of babies born to mothers whose pregnancies were complicated by HG., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Objective: Maternal undernutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. We investigated whether these effects may persist in subsequent generations., Design: Historical cohort study., Setting: Interview during a clinic or home visit or by telephone., Population: Men and women born in the Wilhelmina Gasthuis in Amsterdam between November 1943 and February 1947., Methods: We interviewed cohort members (F1) born around the time of the 1944-45 Dutch famine, who were exposed or unexposed to famine in utero, about their offspring (F2)., Main Outcome Measures: Birthweight, birth length, ponderal index and health in later life (as reported by F1) of the offspring (F2) of 855 participating cohort members, according to F1 famine exposure in utero., Results: F1 famine exposure in utero did not affect F2 (n = 1496) birthweight, but, among the offspring of famine-exposed F1 women, F2 birth length was decreased (-0.6 cm, P adjusted for F2 gender and birth order = 0.01) and F2 ponderal index was increased (+1.2 kg/m(3), P adjusted for F2 gender and birth order = 0.001). The association remained unaltered after adjusting for possible confounders. The offspring of F1 women who were exposed to famine in utero also had poor health 1.8 (95% CI 1.1-2.7) times more frequently in later life (due to miscellaneous causes) than that of F1 unexposed women., Conclusions: We did not find transgenerational effects of prenatal exposure to famine on birthweight nor on cardiovascular and metabolic disease rates. F1 famine exposure in utero was, however, associated with increased F2 neonatal adiposity and poor health in later life. Our findings may imply that the increase in chronic disease after famine exposure in utero is not limited to the F1 generation but persists in the F2 generation.

In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to prenatal famine more often reported a history of breast cancer than nonexposed women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had alterations in reproductive risk factors. Prenatal famine may increase breast cancer incidence.

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by -0.01 g/l (95% confidence interval, -0.14-0.11) in those exposed in late gestation, by -0.03 g/l (-0.16-0.11) in those exposed in mid gestation, and by 0.13 g/l (-0.03-0.30) in those exposed in early gestation, compared with non-exposed people (those born before and those conceived after the famine pooled together). Plasma factor VII concentrations differed by 0.4% (-5.4% to 6.6%) in those exposed to famine in late gestation, by 1.5% (-4.6% to 8.1%) in those exposed in mid gestation. and by -11.8% (-18.4 to -4.8%) in those exposed in early gestation, compared with nonexposed people. Size at birth was not associated with plasma concentrations of fibrinogen or factor VII. Our finding that factor VII concentrations were significantly lower in people whose mothers had been exposed to famine in early pregnancy suggests that liver function may be affected by undernutrition in early gestation.